Precipitation contributes to alleviating pollution of rubber-derived chemicals in receiving watersheds: Combining confluent stormwater runoff from different functional areas.

The release of rubber-derived chemicals (RDCs) in road surface runoff has received significant attention. Urban surface runoff is often the confluence of stormwater runoff from specific areas. However, the impact of precipitation on RDCs contamination in confluent stormwater runoff and receiving watersheds remains poorly understood. Herein, we investigated the profiles of RDCs and their transformation products in confluent stormwater runoff and receiving rivers affected by precipitation events. The results showed that 34 RDCs are ubiquitously present in confluent stormwater runoff and surface water, with mean concentrations of 1.03-2749 and 0.28-436 ng/L, respectively. The most dominant target compounds in each category were N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, 2-benzothiazolol, and 1,3-diphenylguanidine. Total RDCs concentrations in confluent stormwater runoff decreased spatially from industrial areas to business districts to college towns. A significant decrease in RDCs levels in surface water after rainfall was observed (P < 0.01), indicating that precipitation contributes to alleviating RDCs pollution in receiving watersheds. To our knowledge, this is the first report of N,N'-ditolyl-p-phenylenediamine quinone (DTPD-Q) levels in surface waters in China. The annual mass load of ∑RDCs reached 72,818 kg/y in confluent stormwater runoff, while 38,799 kg/y in surface water. The monitoring of confluent stormwater runoff is an efficient measure for predicting contamination loads from RDCs in rivers. Risk assessment suggested that most RDCs posed at least medium risks to aquatic organisms, especially 6PPD-quinone. The findings help to understand the environmental fate and risks of RDCs in the confluent stormwater runoff and receiving environments after precipitation events.

Current dilemma and future directions over prophylactic cranial irradiation in SCLC: a systematic review in MRI and immunotherapy era.

Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with the highest mortality, and the incidence of brain metastasis (BM) is in high frequency. So far, prophylactic cranial irradiation (PCI) has been suggested as an effective treatment for preventing brain metastasis of SCLC. PCI has long been applied to limited-stage SCLC (LS-SCLC) patients who have achieved complete remission after radiotherapy and chemotherapy as a standard treatment. However, the neurocognitive decline is a major concern surrounding PCI. New therapeutic approaches targeting PCI-induced neurotoxicity, including hippocampal protection or memantine, have been increasingly incorporated into the therapeutic interventions of PCI. Helical tomotherapy, RapidArc, and Volumetric-modulated arc therapy (VMAT) with a head-tilting baseplate are recommended for hippocampal protection. Besides, in the MRI and immunotherapy era, the significance of PCI in SCLC patients is controversial. SCLC patients with PCI should be recruited in clinical trials since this is the only way to improve the existing standard of care. This review summarizes the current therapeutic strategy and dilemma over PCI for SCLC, providing a theoretical basis for clinical decision-making and suggestions for PCI practice in clinical.

A novel Anaerobic Cathodic Dynamic Membrane Bioreactor (AnCDMBR) for efficient mitigating fouling and recovering bioenergy from municipal wastewater.

Concerns regarding membrane fouling and suboptimal bioenergy recovery have constrained the implementation of anaerobic membrane bioreactor (AnMBR) for treating low-strength municipal wastewater. This study presents a novel anaerobic cathodic dynamic membrane bioreactor (AnCDMBR) designed to address these challenges. A self-formed cathodic dynamic membrane (CDM) on inexpensive carbon cloth was developed to function as both a membrane and biocathode to achieve dual-function effects of mitigating membrane fouling and accelerating organics conversion. Compared with common dynamic membrane (1.52 kPa/d) and commercial membranes (7.52 kPa/d), the developed CDM presented a significantly reduced fouling rate (1.02 kPa/d), exhibiting the potential as a substitute for high-cost conductive membranes. Furthermore, efficient and stable biomethanation occurred in AnCDMBR with a superior methane yield rate of 0.26 L-CH4/g-COD (CH4 content > 95 %), which was 1.42 times higher than the control, linked to the higher activities of microbial metabolism and methanogenic-related key enzymes. Further analysis revealed that electrostimulation-induced niche differentiation of microbiota regulated interspecies interactions between electroactive microorganisms and complex anaerobic digestion microbiomes, facilitating organic matter conversion to methane and leading to superior bioenergy recovery. This study offered a new strategy for effectively mitigating fouling and recovering bioenergy from low-strength wastewater, potentially expanding the application of AnMBRs.

Towards key genes identification for breast cancer survival risk with neural network models.

Breast cancer, one common malignant tumor all over the world, has a considerably high rate of recurrence, which endangers the health and life of patients. While more and more data have been available, how to leverage the gene expression data to predict the survival risk of cancer patients and identify key genes has become a hot topic for cancer research. Therefore, in this work, we investigate the gene expression and clinical data of breast cancer patients, specifically a novel framework is proposed focusing on the survival risk classification and key gene identification task. We firstly combine the differential expression and univariate Cox regression analysis to achieve dimensional reduction of gene expression data. The median survival time is subsequently proposed as the risk classification threshold and a learning model based on neural network is trained to classify the survival risk of patients. Innovatively, in this work, the activation region visualization technology is selected as the identification tool, which identify 20 key genes related to the survival risk of breast cancer patients. We further analyze the gene function of these 20 key genes based on STRING database. It is critical to learn that, the genetic biomarkers identified in this paper may possess value for the following clinical treatment of breast cancer according to the literature findings. Importantly, the genetic biomarkers identified in this paper may possess value for the following clinical treatment of breast cancer according to the literature findings. Our work accomplishes the objective of proposing a targeted approach to enhancing the survival analysis and therapeutic strategies in breast cancer through advanced computational techniques and gene analysis.

Activity-based metaproteomics driven discovery and enzymological characterization of potential α-galactosidases in the mouse gut microbiome.

The gut microbiota offers an extensive resource of enzymes, but many remain uncharacterized. To distinguish the activities of similar annotated proteins and mine the potentially applicable ones in the microbiome, we applied an effective Activity-Based Metaproteomics (ABMP) strategy using a specific activity-based probe (ABP) to screen the entire gut microbiome for directly discovering active enzymes and their potential applications, not for exploring host-microbiome interactions. By using an activity-based cyclophellitol aziridine probe specific to α-galactosidases (AGAL), we successfully identified and characterized several gut microbiota enzymes possessing AGAL activities. Cryo-electron microscopy analysis of a newly characterized enzyme (AGLA5) revealed the covalent binding conformations between the AGAL5 active site and the cyclophellitol aziridine ABP, which could provide insights into the enzyme's catalytic mechanism. The four newly characterized AGALs have diverse potential activities, including raffinose family oligosaccharides (RFOs) hydrolysis and enzymatic blood group transformation. Collectively, we present a ABMP platform that facilitates gut microbiota AGALs discovery, biochemical activity annotations and potential industrial or biopharmaceutical applications.

The screening of iron oxides for long-term transformation into vivianite to recover phosphorus from sewage.

The reducibility of iron oxides, depending on their properties, influences the kinetics of dissimilatory iron reduction (DIR) during vivianite recovery in sewage. This study elucidated the correlation between properties of iron oxides and kinetics of DIR during the long-term transformation into vivianite, mediated by Geobacter sulfurreducens PCA and sewage. The positive correlation between surface reactivity of iron oxides and reduction rate constant (k) influenced the terminal vivianite recovery efficiency. Akaganeite with the highest adhesion work and surface energy required the lowest reduction energy (Ea), obtained the highest k of 1.36 × 10-2 day-1 and vivianite recovery efficiency of 43 %. The vivianite yield with akaganeite as iron source was 76-164 % higher than goethite, hematite, feroxyhyte, and ferrihydrite in sewage. The distribution of P with akaganeite during DIR in sewage further suggested a more efficient pathway of direct vivianite formation via bio-reduced Fe(II) rather than indirect reduction of ferric phosphate precipitates. Thus, akaganeite was screened out as superior iron source among various iron oxides for vivianite recovery, which provided insights into the fate of iron sources and the cycle of P in sewage.

Construction and preclinical evaluation of a 124I-labelled bispecific antibody targeting PD-L1 and PD-L2.

PURPOSE: NB12 is a bispecific antibody that consists of two anti-programmed cell death-ligand 1 (PD-L1) nanobodies and two anti-programmed cell death-ligand 2 (PD-L2) nanobodies. The aim of this study was to design a novel tracer, [124I]I-NB12, targeting PD-L1/2 and perform preclinical evaluations to dynamically monitor PD-L1/2 expression for determining cancer patient responsiveness to ICI therapy. METHODS: NB12 was labelled with the radionuclide 124I at room temperature (RT). An in vitro binding assay was performed to assess the affinity of [124I]I-NB12 for PD-L1 and PD-L2. Cellular uptake, pharmacokinetic, and biodistribution experiments were performed to evaluate the biological properties. Micro-PET/CT imaging with [124I]I-NB12 was conducted at different time points. Immunohistochemical and haematoxylin and eosin (HE) staining experiments were carried out using tumour tissues. Routine blood, biochemical indices and major organ pathology were used to evaluate the biosafety of the tracers. RESULTS: The radiochemical yield of [124I]I-NB12 was 84.62 ± 3.90%, and the radiochemical purity (RCP) was greater than 99%. [124I]I-NB12 had a high affinity for the PD-L1 (Kd = 19.82 nM) and PD-L2 (Kd = 2.93 nM). Cellular uptake experiments confirmed that the uptake of [124I]I-NB12 by A549-PDL1/2 cells was greater than that by A549 cells. The half-lives of the distribution phase and elimination phase were 0.26 h and 4.08 h, respectively. Micro-PET/CT showed significant [124I]I-NB12 uptake in the tumour region of A549-PDL1/2 tumour-bearing mice compared with A549 tumour-bearing mice 24 h postinjection. Immunohistochemical and HE staining experiments confirmed that tumour-bearing mice was successfully constructed. CONCLUSION: We constructed a bispecific antibody that targets PD-L1 and PD-L2, namely, [124I]I-NB12. Biological evaluation revealed its specificity and affinity for PD-L1/2, and micro-PET/CT confirmed the feasibility of visualizing tumour PD-L1/2 in vivo. Using [124I]I-NB12 may be a promising strategy for identifying cancer patients that can potentially benefit from ICI therapy.

Compound heterozygous mutations of NTNG2 cause intellectual disability via inhibition of the CaMKII signaling.

Netrin-G2 is a membrane-anchored protein and is known to play critical roles in neuronal circuit development and synaptic organization. In this study, we identify compound heterozygous mutations of c.547delC, p.(Arg183Alafs*186) and c.605G>A, p.(Trp202*) in NTNG2 causing a syndrome exhibiting developmental delay, intellectual disability, hypotonia, and facial dysmorphism. To elucidate the underlying cellular and molecular mechanisms, CRISPR-Cas9 technology is employed to generate a knock-in mouse model expressing the R183Afs and W202X mutations. We report that the Ntng2R183Afs/W202X mice exhibit hypotonia and impaired learning and memory. We find that levels of CaMKII and p-GluA1Ser831 are decreased and excitatory postsynaptic transmission and long-term potentiation are impaired. To increase the activity of CaMKII, the mutant mice have received intraperitoneal injections of DCP-LA, a CaMKII agonist, and show improved cognitive function. Together, our findings reveal molecular mechanisms of how NTNG2 deficiency leads to impairments of cognitive ability and synaptic plasticity.

Vitamin D and Cognitive Performance in Older Adults: A Cross-Sectional and Mendelian Randomization Study.

Background: Cognitive decline is a prevalent health problem in older adults, and effective treatments remain to be produced. Serum vitamin D, a commonly used biochemical marker, is widely recognized as an indicator of various diseases. Existing research has not fully elucidated the relationship between vitamin D and cognitive function. The aim of this study is to investigate the real relationship between vitamin D and cognitive function and to identify indicators that have a strong predictive effect on cognitive decline. Methods: At first, we used the dataset of the genome-wide association studies studying vitamin D and cognitive performance to conduct Mendelian randomization analysis. Subsequently, we employed linear regression and smooth curve fitting methods to assess the relationship using the National Health and Nutrition Examination Survey data. Finally, we investigated other predictive features of cognitive performance utilizing a machine learning model. Results: We found that a 1-unit increase in vitamin D is associated with a 6.51% reduction (P < .001) in the risk of cognitive decline. The correlation between vitamin D and cognitive performance is nonlinear, with the inflection point at 79.9 nmol/L (left: ß = 0.043, P < .001; right: ß = -0.007, P = .420). In machine learning, the top 5 predictors are vitamin D, weight, height, age, and body mass index. Conclusion: There is a causal relationship between vitamin D and cognitive performance. 79.9 nmol/L could be the optimal dose for vitamin D supplementation in the elderly. Further consideration of other factors in vitamin D interventions is necessary.

Effects of roxadustat on thyroid hormone levels and blood lipid metabolism in patients undergoing hemodialysis: a retrospective study.

Background: Roxadustat is commonly used to treat renal anemia. However, the potential effects of roxadustat on metabolism and organs other than the kidneys have recently attracted increased attention. Objective: This study aimed to examine the regulatory effects of roxadustat on thyroid hormones and blood lipid metabolism in patients with end-stage kidney disease (ESKD) undergoing hemodialysis. Methods: Eighty ESKD patients on hemodialysis and taking roxadustat were enrolled. Hemoglobin, thyroid hormones (TSH, FT3, FT4), and blood lipid profiles (TC, LDL-C, TG, HDL-C) were assessed before and after treatment. Changes in these parameters were compared, and relevant causative factors were analyzed. Results: Roxadustat significantly increased Hb, lowered TSH, FT4, TC, and LDL-C levels (all P<0.001). Patients were categorized into three groups based on post-treatment TSH inhibition percentage: Q1(≥70%), Q2(30%-70%), Q3(≤30%). Pre-treatment TSH decreased with reduced TSH inhibition (P<0.05). Post-treatment, TC, LDL-C, TSH, FT3, and FT4 increased with reduced TSH inhibition (all P<0.05).TC and LDL-C significantly decreased post-treatment in Q1 and Q2 (P<0.05). Correlation analysis showed a positive correlation between ΔTSH and pre-treatment TSH levels (r=0.732, P<0.001). The proportion of patients with ≥70% TSH inhibition increased with higher pre-treatment TSH levels (P for trend <0.05). ΔLDL-C and ΔTSH were positively correlated (r=0.278, P<0.05), with ΔTSH identified as an influencing factor in multiple linear regression (ß=0.133, 95% CI [0.042, 0.223], P<0.05). Conclusion: Roxadustat effectively improves anemia in ESKD patients while inhibiting TSH and FT4 secretion and reducing TC and LDL-C levels. Decreases in TSH levels correlate with baseline TSH levels, and lowered blood lipid levels are associated with decreased TSH levels.

Detection of ciprofloxacin and pH by carbon dots and rapid, visual sensing analysis.

Food safety is a serious issue worldwide and practical detection method is vital for the supervision of food safety. It is necessary to establish efficient and economical methods to detect antibiotics, especially antibiotics in complex systems. This study employs citric acid and m-phenylenediamine to synthesize N, P-codoped carbon dots (N, P-CDs) by a microwave-assisted method. Anhydrous ethanol and phosphoric acid are essential to the properties of N, P-CDs. A "turn-on" fluorescent probe based on N, P-CDs was established for detecting ciprofloxacin (CIP) with detection limit down to 24.2 nm. Semiquantitative test stripe and a PS color detection system for CIP were developed to achieve visual and smart detection. The test stripe is applied to the visual detection of CIP residues in milk and a popular Chinese cuisine, Malatang, for the first time. N, P-CDs can also be used to detect pH in the range of pH 7.5-12.

Inhalable mucin-permeable nanomicelles deliver antibiotics for effective treatment of chronic pneumonia.

Pseudomonas aeruginosa (P. aeruginosa) pneumonia can have serious physiological consequences, particularly when P. aeruginosa biofilms are formed. Although inhaled therapy is preferred, inhaled drugs tend to get trapped by pulmonary mucus, which hinders efficient antibiotic permeability through mucus and biofilms. In this study, we prepare poly[2-(pentamethyleneimino)ethyl methacrylate]-block-poly[2-(N-oxide-pentamethyleneimino)ethyl methacrylate] (PPEMA-b-PPOEMA) micelles loaded with azithromycin (AZM) using reversible addition-fragmentation chain transfer (RAFT) polymerization to achieve effective treatment of P. aeruginosa pneumonia. The zwitterionic structure on the surface of the micelle facilitates the successful traversal of the mucus and optimal concentration within the biofilm. Furthermore, the protonation of piperidine in the polymer enables the micelles to exhibit a positive charge in the acidic environment of a bacterial infection, enhancing AZM's interaction with the bacterium. Both in vivo and in vitro experiments demonstrate that this transmucosal zwitterionic polymer, in combination with a charge reversal strategy, effectively promotes the enrichment of micelles at the site of bacterial infection, thereby increasing the number of antibiotics reaching the bacterial interior and demonstrating remarkable antibacterial synergy. Overall, this work offers a promising approach for trans-airway drug delivery in the treatment of pneumonia.

H3K36 methyltransferase SMYD2 affects cell proliferation and migration in Hirschsprung's disease by regulating METTL3.

The pathogenesis of Hirschsprung's disease (HSCR) is complex. Recently, it has been found that histone modifications can alter genetic susceptibility and play important roles in the proliferation, differentiation and migration of neural crest cells. H3K36 methylation plays a significant role in gene transcriptional activation and expression, but its pathogenic mechanism in HSCR has not yet been studied. This study aimed to elucidate its role and molecular mechanism in HSCR. Western blot analysis, immunohistochemistry (IHC) and reverse transcription-quantitative PCR (RT‒qPCR) were used to investigate H3K36 methylation and methyltransferase levels in dilated and stenotic colon tissue sections from children with. We confirm that SMYD2 is the primary cause of differential H3K36 methylation and influences cell proliferation and migration in HSCR. Subsequently, quantitative detection of m6A RNA methylation revealed that SMYD2 can alter m6A methylation levels. Western blot analysis, RT-qPCR, co-immunoprecipitation (co-IP), and immunofluorescence colocalization were utilized to confirm that SMYD2 can regulate METTL3 expression and affect m6A methylation, affecting cell proliferation and migration. These results confirm that the H3K36 methyltransferase SMYD2 can affect cell proliferation and migration in Hirschsprung's disease by regulating METTL3. Our study suggested that H3K36 methylation plays an important role in HSCR, confirming that the methyltransferase SMYD2 can affect m6A methylation levels and intestinal nervous system development by regulating METTL3 expression.

Integrative analyses of genes associated with oxidative stress and cellular senescence in triple-negative breast cancer.

Background: Oxidative stress and cellular senescence (OSCS) have great impacts on the occurrence and progression of triple-negative breast cancer (TNBC). This study was intended to construct a prognostic model based on oxidative stress and cellular senescence related difference expression genes (OSCSRDEGs) for TNBC. Methods: The Cancer Genome Atlas (TCGA) databases and two Gene Expression Omnibus (GEO) databases were used to identify OSCSRDEGs. The relationship between OSCSRDEGs and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA), ESTIMATE, and the CIBERSORT algorithm. Least absolute shrinkage and selection operator (LASSO) regression analyses, Cox regression and Kaplan-Meier analysis were employed to construct a prognostic model. Receiver operating characteristic (ROC) curves, nomograms, and decision curve analysis (DCA) were used to evaluate the prognostic efficacy. Gene Set Enrichment Analysis (GSEA) Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to explore the potential functions and mechanism. Results: A comprehensive analysis identified a total of 27 OSCSRDEGs, out of which 15 genes selected for development of a prognostic model. A high degree of statistical significance was observed for the riskscores derived from this model to accurately predict TNBC Overall survival. The decision curve analysis (DCA) and ROC curve analysis further confirmed the superior accuracy of the OSCSRDEGs prognostic model in predicting efficacy. Notably, the nomogram analysis highlighted that DMD exhibited the highest utility within the model. In comparison between high and low OSCScore groups, the infiltration abundance of immune cells was statistically different in the TCGA-TNBC dataset. Conclusion: These studies have effectively identified four essential OSCSRDEGs (CFI, DMD, NDRG2, and NRP1) and meticulously developed an OSCS-associated prognostic model for individuals diagnosed with TNBC. These discoveries have the potential to significantly contribute to the comprehension of the involvement of OSCS in TNBC.

ENU-based dominant genetic screen identifies contractile and neuronal gene mutations in congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital anomaly, but its underlying causes are still not fully understood. It is believed that multiple rare genetic mutations may contribute to the development of CHD. METHODS: In this study, we aimed to identify novel genetic risk factors for CHD using an ENU-based dominant genetic screen in mice. We analyzed fetuses with malformed hearts and compared them to control littermates by whole exome or whole genome sequencing (WES/WGS). The differences in mutation rates between observed and expected values were tested using the Poisson and Binomial distribution. Additionally, we compared WES data from human CHD probands obtained from the Pediatric Cardiac Genomics Consortium with control subjects from the 1000 Genomes Project using Fisher's exact test to evaluate the burden of rare inherited damaging mutations in patients. RESULTS: By screening 10,285 fetuses, we identified 1109 cases with various heart defects, with ventricular septal defects and bicuspid aortic valves being the most common types. WES/WGS analysis of 598 cases and 532 control littermates revealed a higher number of ENU-induced damaging mutations in cases compared to controls. GO term and KEGG pathway enrichment analysis showed that pathways related to cardiac contraction and neuronal development and functions were enriched in cases. Further analysis of 1457 human CHD probands and 2675 control subjects also revealed an enrichment of genes associated with muscle and nervous system development in patients. By combining the mice and human data, we identified a list of 101 candidate digenic genesets, from which each geneset was co-mutated in at least one mouse and two human probands with CHD but not in control mouse and control human subjects. CONCLUSIONS: Our findings suggest that gene mutations affecting early hemodynamic perturbations in the developing heart may play a significant role as a genetic risk factor for CHD. Further validation of the candidate gene set identified in this study could enhance our understanding of the complex genetics underlying CHD and potentially lead to the development of new diagnostic and therapeutic approaches.

Deciphering microbial metabolic interactions and their implications for community dynamics in acid mine drainage sediments.

The microbially-mediated reduction processes have potential for the bioremediation of acid mine drainage (AMD), which represents a worldwide environment problem. However, we know little about the microbial interactions in anaerobic AMD sediments. Here we utilized genome-resolved metagenomics to uncover the nature of cooperative and competitive metabolic interactions in 90 AMD sediments across Southern China. Our analyses recovered well-represented prokaryotic communities through the reconstruction of 2625 population genomes. Functional analyses of these genomes revealed extensive metabolic handoffs which occurred more frequently in nitrogen metabolism than in sulfur metabolism, as well as stable functional redundancy across sediments resulting from populations with low genomic relatedness. Genome-scale metabolic modeling showed that metabolic competition promoted microbial co-occurrence relationships, suggesting that community assembly was dominated by habitat filtering in sediments. Notably, communities colonizing more extreme conditions tended to be highly competitive, which was typically accompanied with increased network complexity but decreased stability of the microbiome. Finally, our results demonstrated that heterotrophic Thermoplasmatota associated with ferric iron and sulfate reduction contributed most to the elevated levels of competition. Our study shed light on the cooperative and competitive metabolisms of microbiome in the hazardous AMD sediments, which may provide preliminary clues for the AMD bioremediation in the future.

A Single Hepatic Metastasis of Cranial Meningioma on [18F]FDG PET/CT 16 Years After Initial Surgery.

Hepatic metastases of cranial meningiomas are rare, particularly when they present as a delayed, solitary metastasis, which poses a challenge for imaging-based diagnosis. [18F]FDG PET/CT facilitates diagnosis and posttreatment restaging, whereas somatostatin receptor-targeted PET demonstrates high sensitivity and specificity in the diagnosis of meningiomas and may potentially evaluate the viability of theranostics approaches, particularly for treatment-resistant meningiomas.

Identification of POU4F1 as a novel prognostic biomarker and therapeutic target in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is a significant global health concern, ranking seventh in incidence and sixth in mortality. It encompasses two pathological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma, with ESCC being more prevalent globally and associated with higher mortality rates. The POU (Pit-Oct-Unc) domain family transcription factors, comprising 15 members, play important roles in embryonic development and organ formation. Aberrant expression of POUs has been observed in several human cancers, influencing cell proliferation, tumor invasion, and drug resistance. However, their specific role in ESCC remains unknown. METHODS: We analyzed TCGA and GEO databases to assess POUs expression in ESCC tissues. Kaplan-Meier and ROC analyses were used to evaluate the prognostic value of POUs. Gene Set Enrichment Analysis and Protein-Protein interaction network were used to explore the potential pathway. Functional assays (Cell Counting Kit-8, EdU Staining assay, and cloning formation assay) and mechanism analyses (RNA-seq, flow cytometry, and Western blot) were conducted to determine the effects of POU4F1 knockdown on ESCC cell phenotypes and signaling pathways. RESULTS: POU4F1 and POU6F2 were upregulated in various cancer tissues, including ESCC, compared to normal tissues. POU4F1 expression was significantly correlated with patient survival and superior to previous models (AUC = 0.776). Knockdown of POU4F1 inhibited ESCC cell proliferation and affected cell cycle, autophagy, and DNA damage pathways in ESCC cells. CONCLUSION: POU4F1 is a novel and promising prognostic and therapeutic target for ESCC patients, providing insights into potential treatment strategies.

Microstructures and High-Temperature Mechanical Properties of Inconel 718 Superalloy Fabricated via Laser Powder Bed Fusion.

The Inconel 718 superalloy demonstrates the potential to fabricate high-temperature components using additive manufacturing. However, additively manufactured Inconel 718 typically exhibits low strength, necessitating post-heat treatments for precipitate strengthening. This study investigated the microstructures and mechanical properties of the Inconel 718 superalloy fabricated via laser powder bed fusion. The room-temperature and high-temperature tensile properties of the Inconel 718 alloy samples following various post-heat treatments were evaluated. The results indicate that the as-built samples exhibited columnar grains with fine cell structures. Solution treatment resulted in δ phase formation and grain recrystallization. Subsequent double aging led to finely distributed nanoscale γ' and γ″ particles. These nanoscale particles provided high strength at both room and high temperatures, resulting in a balanced strength and ductility comparable to the wrought counterpart. High-temperature nanoindentation analyses revealed that the double-aging samples exhibited very high hardness and low creep rates at 650 °C.