Weak magnetic field promotes denitrification by stimulating ferromagnetic ion-containing metalloprotein expression.

Weak magnetic field (WMF) has been recognized to promote biological denitrification processes; however, the underlying mechanisms remain largely unexplored, hindering the optimization of its effectiveness. Here, we systematically investigated the effects of WMF on denitrification performance, enzyme activity, microbial community, and metaproteome in packed bed bioreactors treating high nitrate wastewater under different WMF intensities and C:N ratios. Results showed that WMFs significantly promoted denitrification by consistently stimulating the activities of denitrifying reductases and NAD+/NADH biosynthesis across decreasing C:N ratios. Reductases and electron transfer enzymes involved in denitrification were overproduced due to the significantly enriched overexpression of ferromagnetic ion-containing (FIC) metalloproteins. We also observed WMFs' intensity-dependent selective pressure on microbial community structures despite the effects being limited compared to those caused by changing C:N ratios. By coupling genome-centric metaproteomics and structure prediction, we found the dominant denitrifier, Halomonas, was outcompeted by Pseudomonas and Azoarcus under WMFs, likely due to its structural deficiencies in iron uptake, suggesting that advantageous ferromagnetic ion acquisition capacity was necessary to satisfy the substrate demand for FIC metalloprotein overproduction. This study advances our understanding of the biomagnetic effects in the context of complex communities and highlights WMF's potential for manipulating FIC protein-associated metabolism and fine-tuning community structure.

Optimizing surgical strategies for retroperitoneal liposarcoma: a comprehensive evaluation of standardized aggressive surgical policies.

BACKGROUND: Retroperitoneal liposarcoma (RLPS) constitutes the majority of retroperitoneal sarcomas. While surgical resection remains the sole curative approach, determining the optimal surgical strategy for RLPS remains elusive. This study addresses the ongoing debate surrounding the optimal surgical strategy for RLPS. METHODS: We recruited 77 patients with RLPS who underwent aggressive surgical policies. Patients were categorized into three surgical subtypes: suprapancreatic RLPS, pancreatic RLPS, and subpancreatic RLPS. Our standardized surgical strategy involved resecting macroscopically uninvolved adjacent organs according to surgical subtypes. We collected clinical, pathological and prognostic data for analyses. RESULTS: The median follow-up was 45.5 months. Overall survival (OS) and recurrence-free survival (RFS) were significantly correlated with multifocal RLPS, pathological subtype, recurrent RLPS and histological grade (P for OS = 0.011, 0.004, 0.010, and < 0.001, P for RFS = 0.004, 0.001, < 0.001, and < 0.001, respectively). The 5-Year Estimate OS of well-differentiated liposarcoma (WDLPS), G1 RLPS, de novo RLPS and unifocal RLPS were 100%, 89.4%, 75.3% and 69.1%, respectively. The distant metastasis rate was 1.4%. The morbidity rates (≥ grade III) for suprapancreatic, pancreatic, and subpancreatic RLPS were 26.7%, 15.6%, and 13.3%, respectively. The perioperative mortality rate is 2.6%. CONCLUSIONS: Standardized aggressive surgical policies demonstrated prognostic benefits for RLPS, particularly for G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS. This approach effectively balanced considerations of adequate exposure, surgical safety, and thorough removal of all fat tissue. G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS could be potential indications for aggressive surgical policies.

Development of Fluorenyl-Based Copolyimines with Adjustable Mechanical Properties, Recyclability and Friction Resistance.

Dynamic polyimines are a class of fascinating dynamic polymers with recyclability and reparability owing to their reversible Schiff-base reactions. However, balancing the dynamic properties and mechanical strength of dynamic polyimines presents a major challenge due to the dissociative and associative nature of the imine bonds. Herein, we introduced bulky fluorene groups and polyether amine into the skeleton of polyimine networks to achieve a tradeoff in comprehensive properties. The resulting dynamic polyimines with fluorene groups (Cardo-DPIs) were successfully synthesized by combining the rigid diamine 9,9-bis(4-aminophenyl)fluorene and the flexible polyether amine, demonstrating a high tensile strength of 64.7 MPa. Additionally, Cardo-DPIs films with more content of rigid fluorene groups exhibited higher water resistance, glass transition temperature and wear-resisting ability. Moreover, the Cardo-DPIs films not only efficiently underwent thermal reshaping, but also exhibited excellent self-healing capabilities and chemical degradation in acidic solutions. Furthermore, the resulting films can achieve fully closed-loop recovery by free amine solution for 2 h at room temperature. This study broadens the scope of dynamic polyimine materials and promotes the balanced development of their functional and mechanical properties.

Learning Consistency and Specificity of Cells From Single-Cell Multi-Omic Data.

Advancements in single-cell technologies concomitantly develop the epigenomic and transcriptomic profiles at the cell levels, providing opportunities to explore the potential biological mechanisms. Even though significant efforts have been dedicated to them, it remains challenging for the integration analysis of multi-omic data of single-cell because of the heterogeneity, complicated coupling and interpretability of data. To handle these issues, we propose a novel self-representation Learning-based Multi-omics data Integrative Clustering algorithm (sLMIC) for the integration of single-cell epigenomic profiles (DNA methylation or scATAC-seq) and transcriptomic (scRNA-seq), which the consistent and specific features of cells are explicitly extracted facilitating the cell clustering. Specifically, sLMIC constructs a graph for each type of single-cell data, thereby transforming omics data into multi-layer networks, which effectively removes heterogeneity of omic data. Then, sLMIC employs the low-rank and exclusivity constraints to separate the self-representation of cells into two parts, i.e., the shared and specific features, which explicitly characterize the consistency and diversity of omic data, providing an effective strategy to model the structure of cell types. Feature extraction and cell clustering are jointly formulated as an overall objective function, where latent features of data are obtained under the guidance of cell clustering. The extensive experimental results on 13 multi-omics datasets of single-cell from diverse organisms and tissues indicate that sLMIC observably exceeds the advanced algorithms regarding various measurements.

Double-branched stent graft and four-stage deployment in total arch repair: safety and feasibility evaluation in porcine models.

OBJECTIVES: The primary objective of this research was to evaluate the safety and feasibility of an innovative double-branched stent graft system employing four-stage deployment technology for aortic arch repair in porcine models. METHODS: The double-branched stent graft system consisted of a proximal polyester artificial blood vessel, the main and double-branched stent grafts and a delivery system. We utilized 12 healthy pigs as experimental animals (6 per group). Postimplantation, samples were collected at 90 and 180 days after the operations. Preoperative and postoperative imaging and intraoperative arterial blood gas analyses were performed. After the pigs were euthanized, the implanted product, surrounding tissue and major organs were collected for pathological analysis. RESULTS: The technical success rate of the stent graft implants was 100% (12/12). All animals survived to the experimental end point. Perioperative assessments showed intact stent grafts, and imaging features at the end of the follow-up period revealed neither endoleak nor device migration. No major adverse cardiovascular events were observed during the postoperative follow-up period. Pathological examinations confirmed the satisfactory biocompatibility of the stent graft. CONCLUSIONS: This innovative double-branched stent graft system with four-stage deployment technology was affirmed as a safe and feasible option for aortic arch repair in accordance with our preclinical evaluation with porcine models.

Heterogeneity of molecular subtyping and therapy-related marker expression in primary tumors and paired lymph node metastases of small cell lung cancer.

The classification of molecular subtypes and the identification of targetable molecules have been proposed for small cell lung cancer (SCLC) patients. Our aim was to investigate whether the expression of these markers evaluated using lymph node (LN) metastases represents that of primary tumors. We enrolled 46 surgically resected SCLC patients' primary tumors and paired mediastinal LN metastases. The protein expression of subtype-defining markers (ASCL1, NEUROD1, POU2F3, and YAP1) and therapeutic markers (DLL3, MYC, PD-L1, and MHC I) was examined by immunohistochemistry and was correlated with clinicopathological parameters and prognoses. In primary and metastatic tumors, the expression of these markers was 78.3% and 87.0%, 50.0% and 63.0%, 13.0% and 6.5%, 17.4% and 15.2%, 84.8% and 87.0%, 17.4% and 6.5%, 50.0% and 34.8%, and 60.9% and 37.0%, respectively. Positive tumor PD-L1 expression was less present in LN metastases (p = 0.015), and the same was true for MHC I expression (p = 0.036). NEUROD1 and DLL3 expression levels in metastatic tumors were stronger (p < 0.001 and p = 0.002, respectively); conversely, POU2F3, MYC, PD-L1, and MHC I expression levels were weaker (p = 0.018, p = 0.019, p = 0.001, and p < 0.001, respectively). In 15 (32.6%) patients, we observed a change in the molecular subtyping pattern, and a higher number of neuroendocrine (NE)-high phenotype patients were diagnosed when using the LN specimens (91.3% vs. 84.8%). TNM stage and postoperative chemotherapy were independent prognostic factors in surgically resected SCLC patients, and no prognostic differences were found among molecular subtypes. This study highlights the discordance of subtype-specific proteins and therapeutic markers between SCLC primary tumors and LN metastases. Additionally, our findings have therapeutic and prognostic implications and warrant further clinical investigation.

Effects of stocking density on the homeostasis of uric acid and related liver and kidney functions in ducks.

OBJECTIVE: Stocking density (SD) is an important issue in the poultry industry, which is related to the production performance, intestinal health and immune status. In the present study, the effects of SD on the metabolism and homeostasis of uric acid as well as the related functions of the liver and kidney in ducks were examined. METHODS: A total of 360 healthy 56-day-old Shan-ma ducks were randomly divided into the low stocking density (n = 60, density = 5 birds/m2), medium stocking density (n = 120, density = 10 birds/m2) and high stocking density groups (HSD; n = 180, density = 15 birds/m2). Samples were collected in the 3rd, 6th, and 9th weeks of the experiment for analysis. RESULTS: The serum levels of uric acid, lipopolysaccharide and inflammatory cytokines (interleukin-1ß [IL-1ß], IL-8, and tumor necrosis factor-α [TNF-α]) were increased significantly in the HSD group. Serious histopathological lesions could be seen in both the livers and kidneys in the HSD group in the 9th week. The mRNA expression levels of inflammatory cytokines (IL-8 and TNF-α) and related pathway components (toll-like receptor 4, myeloid differentiation primary response gene 88, and nuclear factor-κB) were increased significantly in both the livers and kidneys in the HSD group. The mRNA expression levels of enzymes (adenosine deaminase, xanthine oxidase, phosphoribosyl pyrophosphate amidotransferase, and phosphoribosyl pyrophosphate synthetase 1) related to the synthesis of uric acid increased significantly in the livers in the HSD group. However, the mRNA expression level of solute carrier family 2 member 9, which plays an important role in the excretion of uric acid by the kidney, was decreased significantly in the kidneys in the HSD group. CONCLUSION: These results indicated that a higher SD could cause tissue inflammatory lesions in the liver and kidney and subsequently affect the metabolism and homeostasis of uric acid, and is helpful for guiding decisions related to the breeding and production of ducks.

Assessing food availability and healthier options in an urban Chinese university: a case study using the Chinese Nutrition Environment Measurement Survey for Stores (C-NEMS-S).

Young adults (18-24 years) in universities are frequently exposed to an environment that promotes unhealthy eating behaviors. Using a validated tool, the Chinese Nutrition Environment Measurement Survey for Stores (C-NEMS-S), we assess the food availability and healthier options in a large, urban Chinese university. We employed C-NEMS-S for scoring criteria and weighting. A total of 52 on-campus canteen outlets were audited in an urban university located in Shijiazhuang City, China. General food outlets (n 43) and self-served food outlets (n 7) were further categorized into eight subtypes. Beverage outlets (n 2) were discussed separately from food outlets. C-NEMS-S scores were significantly different across food outlet types (P = 0.0024), especially between noodle and rice outlets (P = 0.0415). Food availability scores for starchy tubers (P < 0.001), dry beans (P < 0.001), vegetables (P = 0.0225), and fruits (P < 0.001) were significantly different across food outlet subtypes. Healthier options were scarce and only appeared in "grains" (n 2) and "meat and poultry" (n 2) categories. Further research on improving the accustomed audit tool and assessing university student diet quality is warranted.

Volume-based 18F-FDG PET/CT predicts prognosis and outcome of active surveillance for intra-abdominal desmoid tumor.

PURPOSE: Desmoid tumor (DT) is a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Initial active surveillance is recommended by current guideline, and surgery is one of the main therapies for DT. Predicting the prognosis and outcome of active surveillance for intra-abdominal DT is pressing issue. METHODS: The study included eighteen patients with intra-abdominal DT. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured. We analyzed their relationship with the outcome of active surveillance, as well as clinical, prognostic, and pathological data. RESULTS: The MTV and TLG of recurrent DT were significantly higher than those of non-recurrent DT (P < 0.001 and P = 0.00, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing recurrent DT from non-recurrent DT were 760.8 for MTV (sensitivity = 1, specificity = 0.857 and AUC = 0.929), and 1318.4 for TLG (sensitivity = 1, specificity = 0.786, and AUC = 0.911). The cutoff values of MTV and TLG significantly correlated with PFS using the Kaplan-Meier method (P = 0.002 and P = 0.007, respectively). MTV and TLG could distinguish DTs with subsequent progression from stable ones (P = 0.004 and P = 0.004, respectively). The ROC curve suggested that the appropriate cutoff values for distinguishing DTs with subsequent progression from stable ones were 197.1 for MTV (sensitivity = 0.9, specificity = 1, and AUC = 0.900), and 445.45 for TLG (sensitivity = 0.9, specificity = 1, and AUC = 0.900). CONCLUSION: Volume-based 18F-FDG-PET can predict prognosis of intra-abdominal DT. MTV and TLG can predict the outcome of active surveillance for intra-abdominal DT. MTV and TLG can potentially be predictors of surgical risk and difficulty.

Contrastive and adversarial regularized multi-level representation learning for incomplete multi-view clustering.

Incomplete multi-view clustering is a significant task in machine learning, given that complex systems in nature and society cannot be fully observed; it provides an opportunity to exploit the structure and functions of underlying systems. Current algorithms are criticized for failing either to balance data restoration and clustering or to capture the consistency of the representation of various views. To address these problems, a novel Multi-level Representation Learning Contrastive and Adversarial Learning (aka MRL_CAL) for incomplete multi-view clustering is proposed, in which data restoration, consistent representation, and clustering are jointly learned by exploiting features in various subspaces. Specifically, MRL_CAL employs v auto-encoder to obtain a low-level specific-view representation of instances, which restores data by estimating the distribution of the original incomplete data with adversarial learning. Then, MRL_CAL extracts a high-level representation of instances, in which the consistency of various views and labels of clusters is incorporated with contrastive learning. In this case, MRL_CAL simultaneously learns multi-level features of instances in various subspaces, which not only overcomes the confliction of representations but also improves the quality of features. Finally, MRL_CAL transforms incomplete multi-view clustering into an overall objective, where features are learned under the guidance of clustering. Extensive experimental results indicate that MRL_CAL outperforms state-of-the-art algorithms in terms of various measurements, implying that the proposed method is promising for incomplete multi-view clustering.

Optimizing waste molasses utilization to enhance electron transfer via micromagnetic carriers: Mechanisms and high-nitrate wastewater denitrification performance.

The biological denitrification of high-nitrate wastewater (HNW) is primarily hindered by insufficient carbon sources and excessive nitrite accumulation. In this study, micromagnetic carriers with varying micromagnetic field (MMF) strengths (0.0, 0.3, 0.6, 0.9 mT) were employed to enhance the denitrification of HNW using waste molasses (WMs) as a carbon source. The results revealed that 0.6 mT MMF significantly improved the total nitrogen removal (TN) efficiency at 96.3%. A high nitrate (NO3--N) removal efficiency at 99.3% with a low nitrite (NO2--N) accumulation at 25.5 mg/L was achieved at 0.6 mT MMF. The application of MMF facilitated the synthesis of adenosine triphosphate (ATP) and stimulated denitrifying enzymes (e.g., nitrate reductase (NAR), nitrite reductase (NIR), and nitric oxide reductase (NOR)), which thereby promoting denitrification. Moreover, the effluent chemical oxygen demand (COD), tryptophan and fulvic-like substances exhibited their lowest levels at 0.6 mT MMF. Analysis through 16S ribosomal ribonucleic acid gene sequencing indicated a significant enrichment of denitrifying bacteria including Castellaniella Klebsiella under the influence of MMF. Besides, the proliferation of Acholeplasma, Klebsiella and Proteiniphilum at 0.6 mT MMF promoted the hydrolysis and acidification of WMs. This study offers new insights into the enhanced utilization of WMs and the denitrification of HNW through the application of MMF.

Weak magnetic carriers reduce nitrite accumulation and boost denitrification at high nitrate concentrations by enriching functional bacteria and enhancing electron transfer.

Biological denitrification is the dominant method for NO3- removal from wastewater, while high NO3- leads to NO2- accumulation and inhibits denitrification performance. In this study, different weak magnetic carriers (0, 0.3, 0.6, 0.9 mT) were used to enhance biological denitrification at NO3- of 50-2400 mg/L. The effect of magnetic carriers on the removal and mechanism of denitrification of high NO3- was investigated. The results showed that 0.6 and 0.9 mT carriers significantly enhanced the TN removal efficiency (>99%) and reduced the accumulation of NO2- (by > 97%) at NO3- of 1200-2400 mg/L 0.6 and 0.9 mT carriers stimulated microbial electron transport by improving the abundances of coenzyme Q-cytochrome C reductase (by 4.44-23.30%) and cytochrome C (by 2.90-16.77%), which contributed to the enhanced elimination of NO3- and NO2-. 0.6 and 0.9 mT carriers increased the activities of NAR (by 3.74-37.59%) and NIR (by 5.01-8.24%). The abundance of narG genes in 0.6 and 0.9 mT was 1.47-2.35 and 1.38-1.75 times that of R1, respectively, and the abundance of nirS genes was 1.49-2.83 and 1.55-2.39 times that of R1, respectively. Denitrifying microorganisms, e.g., Halomonas, Thauera and Pseudomonas were enriched at 0.6 and 0.9 mT carriers, which benefited to the advanced denitrification performance. This study suggests that weak magnetic carriers can help to enhance the biological denitrification of high NO3- wastewater.

Clonality Analysis for the Relationship between the Pulmonary Combined Neuroendocrine Carcinoma and "the So-Called Reported Histologic Transformation".

Histologic transformation (HT) is common following targeted therapy in adenocarcinoma. However, whether the transformed tumor is a new component or a combined neuroendocrine carcinoma (C-NEC) remains controversial. We aimed to explore the relationship between pulmonary C-NEC and HT. Macro-dissection was performed on different components of surgically resected C-NEC samples. Molecular alterations and clonal evolution were analyzed using whole exome sequencing (WES). The gene statuses for TP53 and RB1 were determined using immunohistochemistry (IHC) and WES to analyze the relationship between C-NEC and reported HT. Sixteen combined small-cell lung cancer patients and five combined large-cell neuroendocrine carcinoma patients were enrolled. The frequency of p53 and Rb inactivation, assessed using IHC in NEC and non-NEC components, was 76.2/76.2% and 66.7/61.9%, respectively. The expression consistency between the components was 81.0 and 85.7% for p53 and Rb, respectively. The frequencies of TP53, RB1, and EGFR mutations, assessed using WES in NEC and non-NEC components, were 81.0/81.0%, 28.6/28.6%, and 42.9/42.9%, respectively. The concordance rates for TP53, RB1, and EGFR were 90.5, 71.4, and 90.5%, respectively. The consistency rate between IHC and WES was 81.0 and 61.9% for TP53 and RB1, respectively. The different components had a common clonal origin for the 21 C-NECs in the clonal analysis, consistent with previous studies on HT. Our study shows that IHC is more sensitive for Rb detection and C-NEC, and the reported HT may be due to differences in evaluations between pathologist and clinicians. Assessing the p53/Rb and EGFR status for such cases would help in recognizing potential transformation cases or uncovering potential combined components.

The association between maternal healthy lifestyle factors during pregnancy and the neonatal anthropometric indicators based on a prospective cohort study.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the associations between a combined healthy lifestyle during the second and third trimesters and offspring anthropometric outcomes in China. METHODS AND STUDY DESIGN: We examined these associations among 548 participants from nine community health centers and three hospitals in the North China cohort. A pregnant women's healthy lifestyle score (HLS) was constructed based on six lifestyle factors: smoking, alcohol consumption, physical activity, sedentary behavior, diet, and gestational weight gain. Anthropometric indicators at birth like birth weight (BW), head circumference (HC), and birth length (BL) were collected, and weight to head circumference ratio (WHC, kg/m), body mass index (BMI, kg/m2) and Ponderal Index (PI, kg/m3) were calculated. Multivariate linear and logistic regression models were used to examine the effects of HLS during the second and third trimesters on anthropometric outcomes at birth, respectively. RESULTS: In fully adjusted models, we found a negative association between second and third-trimester HLS and offspring HC and a positive relationship between second-trimester HLS and BL (p<0.05). Neonates with mothers in the highest HLS tertile had a 5.6% relatively lower HC and 2.3% relatively longer body length than women in the lowest tertile. Each additional unit in third-trimester HLS had an associated decrease in HC by 0.96 cm. None of the associations between HLS and BW, WHC, BMI, and PI of offspring were observed. CONCLUSIONS: A healthy lifestyle score may significantly impact offspring head circumference and body length, supporting the important role of healthy lifestyles in improving the health of offspring.

Preoperative assessment of retroperitoneal Liposarcoma using volume-based 18F-FDG PET/CT: implications for surgical strategy and prognosis.

PURPOSE: Retroperitoneal liposarcoma (RLPS) poses a challenging scenario for surgeons due to its unpredictable biological behavior. Surgery remains the primary curative option for RLPS; however, the need for additional information to guide surgical strategies persists. Volume-based 18F-FDG PET/CT may solve this issue. METHODS: We analyzed data from 89 RLPS patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) and explored their associations with clinical, prognostic, and pathological factors. RESULTS: MTV, TLG of multifocal and recurrent RLPS were significantly higher than unifocal and primary ones (P < 0.001, P < 0.001, P = 0.003 and P = 0.002, respectively). SUVmax correlated with FNCLCC histological grade, mitotic count and Ki-67 index (P for G1/G2 = 0.005, P for G2/G3 = 0.017, and P for G1/G3 = 0.001, P < 0.001 and P = 0.024, respectively). MTG, TLG and SUVmax of WDLPS were significantly lower than DDLPS and PLPS (P for MTV were 0.009 and 0.022, P for TLG were 0.028 and 0.048, and P for SUVmax were 0.027 and < 0.001, respectively). Multivariable Cox analysis showed that MTV > 457.65 (P = 0.025), pathological subtype (P = 0.049) and FNCLCC histological grade (P = 0.033) were related to overall survival (OS). CONCLUSIONS: Our findings indicate that MTV is an independent prognostic factor for RLPS, while MTV, TLG, and SUVmax can preoperatively predict multifocal lesions, histological grade, and pathological subtype. Volume-based 18F-FDG PET/CT offers valuable information to aid in the decision-making process for RLPS surgical strategies.

Corn peptides attenuate non-alcoholic fatty liver disease via PINK1/Parkin-mediated mitochondrial autophagy.

Background: Corn peptides, a novel food prepared from corn gluten meal (CGM) by enzymatic hydrolysis or microbial fermentation, have attracted considerable interest owing to their various bioactive properties. However, the underlying mechanism of corn peptides attenuate non-alcoholic fatty liver disease (NAFLD) remains unclear. Objective: This study aimed to investigate the effect of corn peptides in NAFLD and to decipher the underlying mechanisms. Design: NAFLD was induced by a high-fat diet (HFD) for 10 weeks. Corn peptides were administered during the period. Human hepatocellular carcinomas (HepG2) cells induced by free fatty acids were used for this mechanism study. Results: Corn peptides alleviated HFD-induced histopathological changes, disorders of lipid metabolism, and mitochondrial damage. Moreover, corn peptides blocked mitophagy suppression by HFD based on the increased LC3, ATG7 expressions, as well as decreased P62 levels. Corn peptides increased the expression of proteins involved in fatty acid ß-oxidation, such as PPARα and PGC-1α. Corn peptides also improved the Ser/Thr kinase PINK1 (PINK1) and the E3 ubiquitin ligase Parkin (Parkin) translocation to mitochondria, which is confirmed by immunofluorescence. Furthermore, stable knockdown of PINK1 by PINK1 SiRNA in HepG2 inhibited PINK1-Parkin-associated mitophagy and resulted in lipid accumulation. Conclusion: Corn peptides improved cell injury and ameliorated mitochondrial dysfunction and lipid accumulation via PINK1/Parkin-mediated autophagy in NAFLD. Thus, corn peptides could be a promising nutritional molecule with natural functions for preventing NAFLD.

MAP3K19 Promotes the Progression of Tuberculosis-Induced Pulmonary Fibrosis Through Activation of the TGF-ß/Smad2 Signaling Pathway.

Tuberculosis-induced pulmonary fibrosis (PF) is a chronic, irreversible interstitial lung disease, which severely affects lung ventilation and air exchange, leading to respiratory distress, impaired lung function, and ultimately death. As previously reported, epithelial-mesenchymal transition (EMT) and fibrosis in type II alveolar epithelial cells (AEC II) are two critical processes that contributes to the initiation and progression of tuberculosis-related PF, but the underlying pathological mechanisms remain unclear. In this study, through performing Real-Time quantitative PCR (RT-qPCR), Western blot, immunohistochemistry, and immunofluorescence staining assay, we confirmed that the expression levels of EMT and fibrosis-related biomarkers were significantly increased in lung tissues with tuberculosis-associated PF in vivo and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) strain-infected AEC II cells in vitro. Besides, we noticed that the mitogen-activated protein kinase 19 (MAP3K19) was aberrantly overexpressed in PF models, and silencing of MAP3K19 significantly reduced the expression levels of fibronectin, collagen type I, and alpha-smooth muscle actin to decrease fibrosis, and upregulated E-cadherin and downregulated vimentin to suppress EMT in BCG-treated AEC II cells. Then, we uncovered the underlying mechanisms and found that BCG synergized with MAP3K19 to activate the pro-inflammatory transforming growth factor-beta (TGF-ß)/Smad2 signal pathway in AEC II cells, and BCG-induced EMT process and fibrosis in AEC II cells were all abrogated by co-treating cells with TGF-ß/Smad2 signal pathway inhibitor LY2109761. In summary, our results uncovered the underlying mechanisms by which the MAP3K19/TGF-ß/Smad2 signaling pathway regulated EMT and fibrotic phenotypes of AEC II cells to facilitate the development of tuberculosis-associated PF, and these findings will provide new ideas and biomarkers to ameliorate tuberculosis-induced PF in clinic.

Exploring the molecular features and genetic prognostic factors of pulmonary high-grade neuroendocrine carcinomas.

Molecular research on large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) has progressed significantly. However, there are still fewer molecular markers related to prognostic/therapeutic strategies for these conditions compared to those for adenocarcinoma. We therefore investigated the molecular characteristics of neuroendocrine carcinomas (NECs). We enrolled patients surgically diagnosed with NECs between 2011 and 2019, with complete follow-up records. All were analyzed using whole exome sequencing and p53/Rb immunohistochemistry (IHC). A total of 92 cases, comprising 45 pure SCLC, 15 combined SCLC, 27 pure LCNEC, and 5 combined LCNEC, were included. TP53 (78.3%) and RB1 (34.8%) were the most common molecular alterations, followed by KMT2D, LRP1B, FAT3, NCOR2, SPTA1, and NOTCH1. The mutation frequency for EGFR was 10.9%. Sixteen patients with LCNEC who had TP53/RB1 co-alterations were SCLC-like, while the remaining were NSCLC-like. There was no statistically significant difference between the groups regarding overall survival (OS; p = 0.458) and progression-free survival (PFS; p = 0.157). The frequency of the loss of Rb expression by IHC in SCLC-like LCNEC was 100%. Significant pathway alterations unique to SCLC included Notch and AMPK, while HIF-1 was enriched exclusively in LCNEC. NCOR2 mutation was linked to worse OS (p = 0.029) and PFS (p = 0.015), while wild-type SPTA1 was associated with poor PFS (p = 0.018). IHC for Rb was reliable for predicting LCNEC molecular subtypes, indicating its clinical value. NCOR2 and SPTA1 alterations were identified as prognostic factors that may provide therapeutic targets for patients with NEC.

Molecular subtypes, predictive markers and prognosis in small-cell lung carcinoma.

AIMS: A new molecular subtype classification was proposed for small-cell lung carcinoma (SCLC). We aimed to further validate the classification in various SCLC patient samples using immunohistochemistry (IHC) to highlight its clinical significance. METHODS: We analysed the protein expression of four subtype (achaete-scute family BHLH transcription factor 1 (ASCL1), neuronal differentiation 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3) and Yes1-associated transcriptional regulator (YAP1)) and two predictive markers (delta-like ligand 3 (DLL3) and MYC) using IHC in 216 specimens from 195 SCLC patients, including 21 pairs of resected biopsy tumours. Associations among molecular subtypes, clinicopathological features and prognostic implications were also explored. RESULTS: The ASCL1, NEUROD1, POU2F3, YAP1, DLL3 and MYC-positive expression rates were 70.3%, 56.9%, 14.9%, 19.0%, 75.4% and 22.6%, respectively. DLL3 expression had positive and negative associations with that of ASCL1 and POU2F3/YAP1, respectively, whereas MYC had the opposite effect. Strong associations of ASCL1 (Ρ=0.8603, p<0.0001), NEUROD1 (Ρ=0.8326, p<0.0001), POU2F3 (Ρ=0.6950, p<0.0001) and YAP1 (Ρ=0.7466, p<0.0001) expressions were detected between paired resected biopsy tumours. In addition to SCLC-A (ASCL1-dominant), SCLC-N (NEUROD1-dominant) and SCLC-P (POU2F3-dominant), unsupervised hierarchical cluster analyses identified a fourth, quadruple-negative SCLC subtype (SCLC-QN) characterised by the low expression of all four subtype-specific proteins, and 55.4% (n=108), 27.2% (n=53), 11.8% (n=23) and 5.6% (n=11) were categorised as SCLC-A, SCLC-N, SCLC-P and SCLC-QN, respectively. Significant enrichment of SCLC-P in the combined SCLC cohort was observed, and adenocarcinoma was more prevalent in SCLC-A, while large-cell neuroendocrine carcinoma was more commonly seen in SCLC-P. No survival difference was found among molecular subtypes. CONCLUSIONS: Our results provide clinical insights into the diagnostic, prognostic and predictive significance of SCLC molecular subtype classifications.

Improving the yield and nitrogen use efficiency of hybrid rice through rational use of controlled-release nitrogen fertilizer and urea topdressing.

Introduction: Controlled-release fertilizers effectively improve crop yield and nitrogen use efficiency (NUE). However, their use increases the cost of crop production. Optimal management modes involving urea replacement with controlled-release N fertilizers to increase rice yield through enhanced NUE are not widely explored. Methods: Field experiments were conducted from 2017 to 2018 to determine the effects of different controlled-release N fertilizers combined with urea [urea-N (180 kg ha-1, N1)]. We used controlled-release N (150 kg ha-1, N2) as the base, and four controlled-release N and urea-N ratio treatments [(80%:0% (N3), 60%:20% (N4), 40%:40% (N5), or 20%:60% (N6) as the base with 20% urea-N as topdressing at the panicle initiation stage under 150 kg ha-1] to study their impact on the grain yield and NUE of machine-transplanted rice. Results and discussion: Grain yield and NUE were positively correlated with increases in photosynthetic production, flag leaf net photosynthetic rate (Pn), root activity, N transport, and grain-filling characteristics. The photosynthetic potential and population growth rate from the jointing to the full-heading stage, highly effective leaf area index (LAI) rate and Pn at the full-heading stage, root activity at 15 d after the full-heading stage, and N transport in the leaves from the full-heading to mature stage were significantly increased by the N4 treatment, thereby increasing both grain yield and NUE. Furthermore, compared with the other N treatments, the N4 treatment promoted the mean filling rate of inferior grains, which is closely related to increased filled grains per spikelet and filled grains rate. These effects ultimately improved the grain yield (5.03-25.75%), N agronomic efficiency (NAE, 3.96-17.58%), and N partial factor productivity (NPP, 3.98-27.13%) under the N4 treatment. Thus, the N4 treatment with controlled-release N (60%) and urea-N (20%) as a base and urea-N (20%) as topdressing at the panicle-initiation stage proved effective in improving the grain yield and NUE of machine-transplanted hybrid indica rice. These findings offer a theoretical and practical basis for enhancing rice grain yield, NUE, and saving the cost of fertilizer.