KLF10/CBS increases the sensitivity of gastric carcinoma cells to methionine restriction by promoting sulfur transfer pathway.

Gastric cancer metastasis is a major cause of poor prognosis. Our previous research showed that methionine restriction (MR) lowers the invasiveness and motility of gastric carcinoma. In this study, we investigated the particular mechanisms of MR on gastric carcinoma metastasis. In vitro, gastric carcinoma cells (AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45) were grown in an MR medium for 24 h. In vivo, BALB/c mice were given a methionine-free (Met-) diet. Transwell assays were used to investigate cell invasion and migration. The amounts of Krüppel like factor 10 (KLF10) and cystathionine ß-synthase (CBS) were determined using quantitative real-time PCR and Western blot. To determine the relationship between KLF10 and CBS, chromatin immunoprecipitation and a dual-luciferase reporter experiment were used. Hematoxylin-eosin staining was used to detect lung metastasis. Liquid chromatography-mass spectrometry was used to determine cystathionine content. MR therapy had varying effects on the invasion and migration of gastric carcinoma cells AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45. KLF10 was highly expressed in AGS cells but poorly expressed in KATO III cells. KLF10 improved MR's ability to prevent gastric carcinoma cell invasion and migration. In addition, KLF10 may interact with CBS, facilitating transcription. Further detection revealed that inhibiting the KLF10/CBS-mediated trans-sulfur pathway lowered Met-'s inhibitory effect on lung metastasis development. KLF10 transcription activated CBS, accelerated the trans-sulfur pathway, and increased gastric carcinoma cells' susceptibility to MR.

Controlling the Selectivity of Electrocatalytic NO Reduction through pH and Potential Regulation on Single-Atom Catalysts.

Electrocatalytic nitrogen oxide reduction (NOxRR) emerges as an effective way to bring the disrupted nitrogen cycle back into balance. However, efficient and selective NOxRR is still challenging partly due to the complex reaction mechanism, which is influenced by experimental conditions such as pH and electrode potential. Here, we have studied the enzyme-inspired iron single-atom catalysts (Fe-N4-C) and identified that the selectivity roots in the first step of the nitric oxide reduction. Combining the constrained molecular dynamics (MD) simulations with the quasi-equilibrium approximation, the effects of electrode potential and pH on the reaction free energy were considered explicitly and predicted quantitatively. Systematic heat maps for selectivity between single-N and N-N-coupled products in a wide pH-potential space are further developed, which have reproduced the experimental observations of NOxRR. The approach presented in this study allows for a realistic simulation of the electrocatalytic interfaces and a quantitative evaluation of interfacial effects. Our results in this study provide valuable and straightforward guidance for selective NOx reduction toward desired products by precisely designing the experimental conditions.

Merging DNA Repair with Bioorthogonal Conjugation Enables Accessible and Versatile Asymmetric DNA Catalysis.

Optimizing catalysts through high-throughput screening for asymmetric catalysis is challenging due to the difficulty associated with assembling a library of catalyst analogues in a timely fashion. Here, we repurpose DNA excision repair and integrate it with bioorthogonal conjugation to construct a diverse array of DNA hybrid catalysts for highly accessible and high-throughput asymmetric DNA catalysis, enabling a dramatically expedited catalyst optimization process, superior reactivity and selectivity, as well as the first atroposelective DNA catalysis. The bioorthogonality of this conjugation strategy ensures exceptional tolerance toward diverse functional groups, thereby facilitating the facile construction of 44 DNA hybrid catalysts bearing various unprotected functional groups. This unique feature holds the potential to enable catalytic modalities in asymmetric DNA catalysis that were previously deemed unattainable.

Competitive Formation Mechanism for Bidentate Passivation of Halogen Vacancies in Perovskite Based on 6-Chloropurine.

For metal halide perovskite solar cells, bidentate passivation (BP) is highly effective, but currently, only passivation sites rather than molecular environments are being considered. Here, the authors report an effective approach for high-performance fully printable mesoscopic perovskite solar cells (FP-PSCs) through the BP strategy using the multidentate molecule 6-chloropurine (6-CP). By utilizing density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR) characterizations, the competition mechanism is identified of BP between the chlorine atom and neighboring nitrogen atom of the imidazole and pyrimidine rings. Through BP between the chlorine atom and adjacent nitrogen atom in imidazole, the power conversion efficiency (PCE) of the pristine samples is significantly enhanced from 16.25% to 17.63% with 6-CP. The formation of BP enhances interfacial hole selectivity and charge transfer, and suppresses nonradiative recombination, improving device stability under high humidity conditions. The competition mechanism of BP between two aromatic cycles provides a path for designing molecular passivants and selecting passivation pathways to approach theoretical limits.

Methionine restriction attenuates the migration and invasion of gastric cancer cells by inhibiting nuclear p65 translocation through TRIM47.

The prevention and treatment of gastric cancer has been the focus and difficulty of medical research. We aimed to explore the mechanism of inhibiting migration and invasion of gastric cancer cells by methionine restriction (MR). The human gastric cancer cell lines AGS and MKN45 cultured with complete medium (CM) or medium without methionine were used for in vitro experiments. MKN45 cells were injected tail vein into BALB/c nude mice and then fed with normal diet or methionine diet for in vivo experiments. MR treatment decreased cell migration and invasion, increased E-cadherin expression, decreased N-cadherin and p-p65 expressions, and inhibited nuclear p65 translocation of AGS and MKN45 cells when compared with CM group. MR treatment increased IκBα protein expression and protein stability, and decreased IκBα protein ubiquitination level and TRIM47 expression. TRIM47 interacted with IκBα protein, and overexpression of TRIM47 reversed the regulatory effects of MR. TRIM47 promoted lung metastasis formation and partially attenuated the effect of MR on metastasis formation in vivo compared to normal diet group mice. MR reduces TRIM47 expression, leads to the degradation of IκBα, and then inhibits the translocation of nuclear p65 and the migration and invasion of gastric cancer cells.

Dispersion Behavior of a Droplet Impacting a Single Fiber.

The high-gravity reactor, known for its excellent mass transfer capability, plays a crucial role in the carbon capture process. The wire mesh packing serves as the core structure for enhancing mass transfer performance. Understanding the underlying dispersion mechanism requires a thorough exploration of the dynamics of droplet impact on a single fiber. This work aimed to numerically study the process of a droplet impacting a single fiber by applying the volume of fluid method. The effects of initial velocity (u0), initial diameter (D0), impact eccentric distance (e), and impact angle (θ) on the deformation evolution and dispersion characteristics of a droplet impacting a single fiber were systematically studied. Central or vertical impacts can be categorized into four main stages: splitting, merging, stretching, and breaking. Meanwhile, asynchronous breaking, sliding splitting, and oblique stages were observed during eccentric and nonvertical impacts. Subsequently, dimensionless time (t*) and the rate of increase of the gas-liquid interfacial area (η) were introduced to quantitatively analyze the dispersion characteristics postimpact. Increasing the initial velocity, reducing the droplet diameter, minimizing the impact eccentric distance, and maximizing the impact angle all contribute to enhanced dispersion performance. A correlation for the maximum increase rate of the gas-liquid interfacial area of the droplet was proposed, with errors less than ±15%. Finally, the deformation mechanism of droplet impact on a fiber was summarized by analyzing the influences of differential pressure inside and outside the liquid film, as well as gas vortices.

Green Synthesis of Polyurethane Sponge-Grafted Calcium Alginate with Carbon Ink Aerogel with High Water Vapor Harvesting Capacity for Solar-Driven All-Weather Atmospheric Water Harvesting.

Atmospheric water harvesting (AWH) technology is a new strategy for alleviating freshwater scarcity. Adsorbent materials with high hygroscopicity and high photothermal conversion efficiency are the key to AWH technology. Hence, in this study, a simple and large-scale preparation for a hygroscopic compound of polyurethane (PU) sponge-grafted calcium alginate (CA) with carbon ink (SCAC) was developed. The PU sponge in the SCAC aerogel acts as a substrate, CA as a moisture adsorber, and carbon ink as a light adsorber. The SCAC aerogel exhibits excellent water absorption of 0.555-1.40 g·g-1 within a wide range of relative humidity (40-80%) at 25 °C. The SCAC aerogel could release adsorbed water driven by solar energy, and more than 92.17% of the adsorbed water could be rapidly released over a wide solar intensity range of 1.0-2.0 sun. In an outdoor experiment, 57.517 g of SCAC was able to collect 32.8 g of clean water in 6 h, and the water quality meets the drinking water standards set by the World Health Organization. This study suggests a new approach to design promising AWH materials and infers the potential practical application of SCAC aerogel-based adsorbents.

Anion Photoelectron Spectroscopy and Quantum Chemistry Calculations of Gas-Phase TaSi17Ì and TaSi18Ì Clusters: Structural Determination, Bonding Characteristics, and Multiplicity of Structural Forms.

This study explores the structures and chemical bonding properties of TaSi17̅ and TaSi18̅ clusters by employing anion photoelectron spectroscopy and theoretical computations. Utilizing CALYPSO and ABCluster programs for initial structure prediction, B3LYP hybrid functional for optimization, and CCSD(T)/def2-TZVPPD level for energy calculations, the research identifies the most stable isomers of these clusters. Key findings include the identification of two coexisting low-energy isomers for TaSi17̅, exhibiting Ta-endohedral fullerene-like cage structures, and the lowest-energy structures of TaSi17̅ and TaSi18̅ anions can be considered as derived from the TaSi16̅ superatom cluster. The study enhances the understanding of group 14 element chemistry and guides the design of novel inorganic metallic compounds, potentially impacting materials science.

Elucidation of the Biosynthesis of Griseoluteic Acid in Streptomyces griseoluteus P510.

Phenazines are aromatic compounds with antifungal and cytotoxic activities. Phenazines incorporating phenazine 1-carboxylic acid have widespread applications in agriculture, medicine, and industry. Griseoluteic acid is a cytotoxic compound secreted by Streptomyces griseoluteus P510, displaying potential medical applications. However, the biosynthetic pathway of griseoluteic acid has not been elucidated, limiting its development and application. In this study, a conserved phenazine biosynthetic gene cluster of S. griseoluteus P510 was identified through genomic analysis. Subsequently, its was confirmed that the four essential modification enzymes SgpH, SgpI, SgpK, and SgpL convert phenazine-1,6-dicarboxylic acid into griseoluteic acid by heterologous expression in Escherichia coli. Moreover, the biosynthetic pathway of griseoluteic acid was established in Pseudomonas chlororaphis characterized by a high growth rate and synthesis efficiency of phenazines, laying the foundation for the efficient production of griseoluteic acid.

APOE ε4 allele modifies the associations of toxic metals and their mixture with cognitive impairment among older adults.

BACKGROUND: The evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people. METHODS: A total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment. RESULTS: Pb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (Ptrend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR=1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively. CONCLUSIONS: APOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention.

Biochar alleviates inhibition effects of humic acid on anaerobic digestion: Insights to performances and mechanisms.

To recover methane from waste activated sludge through anaerobic digestion (AD) is one promising alternative to achieve carbon neutrality for wastewater treatment plants. However, humic acids (HAs) are one of the major compositions in waste activated sludge, and their accumulation performs inhibition effects on AD. This study investigated the potentials of biochar (BC) in alleviating inhibition effects of HAs on AD. Results showed that although the accumulated HAs reduced methane yield by 9.37% compared to control, the highest methane yield, 132.6 mL CH4/g VSS, was obtained after adding BC, which was 45.9% higher than that in HA group. Mechanism analysis showed that BC promoted the activities of hydrolase such as protease and α-glucosidase, which were 69.7% and 29.7% higher than those in HA group, respectively. The conversion of short-chain fatty acids was accelerated. In addition, the evolutions of electroactive microorganisms like Clostridium_sensu_stricto_13 and Methanosaeta were consistent with the activitiies of electron transfer and the contents of cytochrome c. Furthermore, parts of HAs rather than all of them were adsorbed by BC, and the remaining free HAs and BC formed synergistic effects on methanogenesis, then both CO2 reduction and acetoclastic methanogenesis pathways were improved. The findings may provide some solutions to alleviate inhibition effects of HAs on AD.

Unveiling the structural and bonding properties of AuSi2- and AuSi3- clusters: A comprehensive analysis of anion photoelectron spectroscopy and ab initio calculations.

Silicon clusters infused with transition metals, notably gold, exhibit distinct characteristics crucial for advancing microelectronics, catalysts, and energy storage technologies. This investigation delves into the structural and bonding attributes of gold-infused silicon clusters, specifically AuSi2- and AuSi3-. Utilizing anion photoelectron spectroscopy and ab initio computations, we explored the most stable isomers of these clusters. The analysis incorporated Natural Population Analysis, electron localization function, molecular orbital diagrams, adaptive natural density partitioning, and Wiberg bond index for a comprehensive bond assessment. Our discoveries reveal that cyclic configurations with the Au atom atop the Si-Si linkage within the fundamental Si2 and Si3 clusters offer the most energetically favorable structures for AuSi2- and AuSi3- anions, alongside their neutral counterparts. These anions exhibit notable highest occupied molecular orbital-lowest unoccupied molecular orbital gaps and significant σ and π bonding patterns, contributing to their chemical stability. Furthermore, AuSi2- demonstrates π aromaticity, while AuSi3- showcases a distinctive blend of σ antiaromaticity and π aromaticity, crucial for their structural robustness. These revelations expand our comprehension of gold-infused silicon clusters, laying a theoretical groundwork for their potential applications in high-performance solar cells and advanced functional materials.

Structural evolution and bonding properties of Nb1-2Gen-/0 (n = 3-7) clusters: Anion photoelectron spectroscopy and theoretical calculations.

This study presents a collaborative experimental and theoretical investigation into the structures and electronic properties of niobium-doped germanium clusters. Anion photoelectron spectra for Nb1-2Gen- (n = 3-7) clusters were acquired using 266 nm photon energies, enabling the determination of adiabatic detachment energies and vertical detachment energies. In conjunction with these experimental measurements, density functional theory (DFT) calculations were conducted to validate the experimentally obtained electron detachment energies and elucidate the geometric and electronic structures of each anionic cluster. The agreement between DFT calculations and experimental data establishes a solid foundation for assessing the structural evolution and electronic properties of niobium-doped germanium clusters. It is noted that both neutral and anionic clusters exhibit predominantly similar overall structural characteristics, with the exception of Nb2Ge6- and Nb2Ge6. Furthermore, this investigation emphasizes the exceptional chemical stability of the D3d symmetric chair-shaped structure in Nb2Ge6-, providing insights into its bonding characteristics.

Solvation enhanced long-range proton transfer in aqueous phase for glycolaldehyde hydrogenation over Ru/C catalyst.

The catalytic hydrogenation of biomass-derived chemicals is essential in chemical industry due to the growing demand for sustainable and renewable energy sources. In this study, we present a comprehensive theoretical investigation regarding the hydrogenation of glycolaldehyde to ethylene glycol over a Ru/C catalyst by employing density functional theory and ab initio molecular dynamics simulations. With inclusion of explicit solvation, we have demonstrated that the glycolaldehyde hydrogenation is significantly improved due to the fast proton transfer through the hydrogen bond network. The enhanced activity could be attributed to the participation of the solvent water as the hydrogen source and the highly positively charged state of a Ru cluster in an aqueous phase, which are critical for the activation of aldehyde groups and proton-assisted hydrogenation. Overall, our findings provide valuable insights into glycolaldehyde hydrogenation over Ru/C catalysts in the aqueous phase, highlighting the importance of solvation effects in the biomass conversion.

Diagnosis of membranous nephropathy with Anti-GBM glomerulonephritis: a case series report.

BACKGROUND: The concomitant occurrence of membranous nephropathy and anti-glomerular basement (anti-GBM) disease has been previously described but is extremely rare. However, delayed recognition or misdiagnosis leads to delayed treatment, resulting in worse renal and patient outcomes. CASE PRESENTATION: We present 3 patients with rapidly progressive glomerulonephritis (RPGN), anti-GBM and serum-positive M-type phospholipase A2 receptor (anti-PLA2R) antibody. Renal biopsies revealed PLA2R-associated membranous nephropathy with anti-GBM glomerulonephritis. We analyzed the clinical and pathological characteristics and discussed that the correct diagnosis of membranous nephropathy with anti-GBM should rely on a combination of renal biopsy findings and serological testing. Despite aggressive treatment, one patient received maintenance hemodialysis, one patient progressed to CKD 3 stage, and the other patient died of cerebral infarction. CONCLUSION: The simultaneous occurrence of membranous nephropathy and anti-GBM disease is extremely rare. The correct diagnosis of membranous nephropathy with anti-GBM relies on a combination of renal biopsy findings and serological testing. Early diagnosis is needed to improve the renal dysfunction.

Upregulation of E-cadherin by the combination of methionine restriction and HDAC2 intervention for inhibiting gastric carcinoma metastasis.

Invasion and metastasis are the leading causes of death in individuals with malignant tumors, including gastric cancer. In this study, we aim to explore the effect and related mechanisms of methionine restriction (MR) on gastric carcinoma metastasis. In the MR cell model, gastric carcinoma cells are cultured in the MR medium, and in the animal model, BALB/c nude rodents are administered with a methionine-free diet after receiving injections of MKN45 cells into the caudal vein. Transwell assay is used to detect cell invasion and migration. Chromatin immunoprecipitation is performed to investigate the levels of H3K9me2, H3K27Ac, and H3K27me3 in the E-cadherin promoter. The results show that MR inhibits gastric carcinoma cell migration, invasion, and lung metastasis. MR increases E-cadherin while reducing the H3K27me3 level in the E-cadherin promoter. E-cadherin expression in gastric carcinoma cells is adversely regulated by HDAC2. Overexpressing HDAC2 reduces the H3K27Ac level in the E-cadherin promoter, while interfering with HDAC2 increases the H3K27Ac level. HDAC2 interference under MR conditions further upregulates E-cadherin expression and inhibits gastric carcinoma cell migration, invasion, and lung metastasis. MR combined with HDAC2 interference promotes E-cadherin expression by mediating the methylation and acetylation of E-cadherin, thus inhibiting the invasion, migration, and lung metastasis of gastric carcinoma cells. Our study provides a new theoretical basis for the inhibitory effect of MR on gastric cancer.

Vestigial mediates the effect of insulin signaling pathway on wing-morph switching in planthoppers.

Wing polymorphism is an evolutionary feature found in a wide variety of insects, which offers a model system for studying the evolutionary significance of dispersal. In the wing-dimorphic planthopper Nilaparvata lugens, the insulin/insulin-like growth factor signaling (IIS) pathway acts as a 'master signal' that directs the development of either long-winged (LW) or short-winged (SW) morphs via regulation of the activity of Forkhead transcription factor subgroup O (NlFoxO). However, downstream effectors of the IIS-FoxO signaling cascade that mediate alternative wing morphs are unclear. Here we found that vestigial (Nlvg), a key wing-patterning gene, is selectively and temporally regulated by the IIS-FoxO signaling cascade during the wing-morph decision stage (fifth-instar stage). RNA interference (RNAi)-mediated silencing of Nlfoxo increase Nlvg expression in the fifth-instar stage (the last nymphal stage), thereby inducing LW development. Conversely, silencing of Nlvg can antagonize the effects of IIS activity on LW development, redirecting wing commitment from LW to the morph with intermediate wing size. In vitro and in vivo binding assays indicated that NlFoxO protein may suppress Nlvg expression by directly binding to the first intron region of the Nlvg locus. Our findings provide a first glimpse of the link connecting the IIS pathway to the wing-patterning network on the developmental plasticity of wings in insects, and help us understanding how phenotypic diversity is generated by the modification of a common set of pattern elements.

Hydroxychloroquine exacerbates imiquimod-induced psoriasis-like dermatitis through stimulating overexpression of IL-6 in keratinocytes.

OBJECTIVE: Hydroxychloroquine (HCQ) is a US Food and Drug Administration (FDA)-approved treatment for systemic lupus erythematosus (SLE) through inhibition of antigen presentation and subsequent reduction in T cell activation. Psoriasis relapse after antimalarial therapy have been reported in up to 18% of patients with psoriasis. Here, we explored the role of HCQ on exacerbating dermatitis utilizing an imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model. METHODS: Thirty-six C57BL/6 female mice were divided into six groups: wild-type control, IMQ-Only, pre-treat HCQ (30 mg/kg and 60 mg/kg HCQ), and co-treat HCQ with IMQ (30 mg/kg and 60 mg/kg HCQ). Besides control, all were topically treated with IMQ for 5 days. Pharmacological effects and mechanisms of HCQ were assessed by clinical severity of dermatitis, histopathology, and flow cytometry. HaCaT cells were co-treated with both HCQ and recombinant IL-17A, followed by the detection of proinflammatory cytokine expression and gene profiles through enzyme-linked immunosorbent assay and next-generation sequencing. RESULTS: In the pre-treated and co-treated HCQ groups, skin redness and scaling were significantly increased compared to the IMQ-Only group, and Th17 cell expression was also upregulated. Acanthosis and CD11b+IL23+ dendritic cell (DC) infiltration were observed in the HCQ treatment group. IL-6 overexpression was detected in both the HaCaT cells and skin from the experimental mice. Psoriasis-related genes were regulated after being co-treated with HCQ and recombinant IL-17A in HaCaT cells. CONCLUSIONS: HCQ exacerbates psoriasis-like skin inflammation by increasing the expression of IL-6, stimulating DC infiltration, and promoting Th17 expression in the microenvironment of the skin. KEY MESSAGES: This study provided possible mechanisms for inducing psoriasis during HCQ treatment through an animal model.

Characteristics and risk differences of different tumor sizes on distant metastases of pancreatic neuroendocrine tumors: A retrospective study in the SEER database.

BACKGROUND: The rate of distant metastasis in patients with pancreatic neuroendocrine tumors (PNETs) is 20%-50% at the time of initial diagnosis. However, whether tumor size can predict distant metastasis for PNETs remains unknown up to date. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) population-based data to collect 6089 patients with PNETs from 2010 to 2019. The optimal cut-off point of tumor size to predict distant metastasis was calculated by Youden's index. Multivariate logistic regression analysis was used to figure out the association between tumor size and distant metastasis patterns. RESULTS: The most common metastatic site was liver (27.2%), followed by bone (3.0%), lung (2.3%) and brain (0.4%). Based on an optimal cut-off value of tumor size (25.5 mm) for predicting distant metastasis determined by Youden's index, patients were categorized into groups of tumor size < 25.5 mm and ≥ 25.5 mm. Multivariate logistic regression analyses showed that, compared with < 25.5 mm, tumor size ≥ 25.5 mm was an independent risk predictor of overall distant metastasis [odds ratio (OR) = 4.491, 95% confidence interval (CI): 3.724-5.416, P < 0.001] and liver metastasis (OR = 4.686, 95% CI: 3.886-5.651, P < 0.001). CONCLUSIONS: Tumor size ≥ 25.5 mm was significantly associated with more overall distant and liver metastases. Timely identification of distant metastasis for tumor size ≥ 25.5 mm may provide survival benefit for timely and precise treatment.

Gender associations between phthalate exposure and biomarkers of oxidative stress: A prospective cohort study.

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.