KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Iron-Nitrogen Amendment Reduced Perfluoroalkyl Acids' Phyto-Uptake in the Wheat-Soil Ecosystem: Contributions of Dissolved Organic Matters in Soil Solution and Root Extracellular Polymeric Substances.

Understanding the mechanisms underlying perfluoroalkyl acids (PFAAs) translocation, distribution, and accumulation in wheat-soil ecosystems is essential for agricultural soil pollution control and crop ecological risk assessment. This study systematically investigated the translocation of 13 PFAAs under different iron and nitrogen fertilization conditions in a wheat-soil ecosystem. Short-chain PFAAs including PFBA, PFPeA, PFHxA, and PFBS mostly accumulated in soil solution (10.43-55.33%) and soluble extracellular polymeric substances (S-EPS) (11.39-14.77%) by the adsorption to amino- (-NH2) and hydroxyl (-OH) groups in dissolved organic matter (DOM). Other PFAAs with longer carbon chain lengths were mostly distributed on the soil particle surface by hydrophobic actions (74.63-94.24%). Iron-nitrogen amendments triggered (p < 0.05) soil iron-nitrogen cycling, rhizospheric reactive oxygen species fluctuations, and the concentration increases of -NH2 and -OH in the DOM structure. Thus, the accumulation capacity of PFAAs in soil solution and root EPS was increased. In sum, PFAAs' translocation from soil particles to wheat root was synergistically reduced by iron and nitrogen fertilization through increased adsorption of soil particles (p < 0.05) and the retention of soil solution and root EPSs. This study highlights the potential of iron-nitrogen amendments in decreasing the crop ecological risks to PFAAs' pollution.

Spatial analysis of stromal signatures identifies invasive front carcinoma-associated fibroblasts as suppressors of anti-tumor immune response in esophageal cancer.

BACKGROUND: Increasing evidence indicates that the tumor microenvironment (TME) is a crucial determinant of cancer progression. However, the clinical and pathobiological significance of stromal signatures in the TME, as a complex dynamic entity, is still unclear in esophageal squamous cell carcinoma (ESCC). METHODS: Herein, we used single-cell transcriptome sequencing data, imaging mass cytometry (IMC) and multiplex immunofluorescence staining to characterize the stromal signatures in ESCC and evaluate their prognostic values in this aggressive disease. An automated quantitative pathology imaging system determined the locations of the lamina propria, stroma, and invasive front. Subsequently, IMC spatial analyses further uncovered spatial interaction and distribution. Additionally, bioinformatics analysis was performed to explore the TME remodeling mechanism in ESCC. To define a new molecular prognostic model, we calculated the risk score of each patient based on their TME signatures and pTNM stages. RESULTS: We demonstrate that the presence of fibroblasts at the tumor invasive front was associated with the invasive depth and poor prognosis. Furthermore, the amount of α-smooth muscle actin (α-SMA)+ fibroblasts at the tumor invasive front positively correlated with the number of macrophages (MØs), but negatively correlated with that of tumor-infiltrating granzyme B+ immune cells, and CD4+ and CD8+ T cells. Spatial analyses uncovered a significant spatial interaction between α-SMA+ fibroblasts and CD163+ MØs in the TME, which resulted in spatially exclusive interactions to anti-tumor immune cells. We further validated the laminin and collagen signaling network contributions to TME remodeling. Moreover, compared with pTNM staging, a molecular prognostic model, based on expression of α-SMA+ fibroblasts at the invasive front, and CD163+ MØs, showed higher accuracy in predicting survival or recurrence in ESCC patients. Regression analysis confirmed this model is an independent predictor for survival, which also identifies a high-risk group of ESCC patients that can benefit from adjuvant therapy. CONCLUSIONS: Our newly defined biomarker signature may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for reversing the fibroblast-mediated immunosuppressive microenvironment.

Effects of Escherichia pollution and salinity on nutrient levels in submerged vegetated wetlands: Insights into benthic community stability and metabolisms.

Inner coastal wetland ecosystems are generally eutrophic and are often exposed to both salinity stress and Escherichia coli pollution. However, the effects of these stressors on nutrient-cycling and microbial communities are under-researched. Here, we established a vegetated wetland ecosystem in a saline environment to understand the effects of E. coli pollution on nutrient removal and benthic microorganisms. The results show that E. coli significantly inhibited nutrient removal, especially total nitrogen (TN) and ammonium (78.89-84.98 and 3.45-44.65% were removed from the non-E. coli-treated and the E. coli-treated water, respectively). Compared with non-vegetated systems, archaeal community variations at both compositional and phylogenetic levels were weakened in vegetated systems (p < 0.05). Among all the environmental factors, the ratios of PO43--P to total phosphorus and NO3--N to TN contributed the most to archaeal and bacterial community structural variations, respectively. E. coli pollution affected archaeal community succession more than bacteria (p < 0.05). E. coli also weakened the trophic transferring efficiencies between Cyanobacteria and Myxobacteria (p < 0.05). Metabolically, E. coli inhibited bacterial genetic metabolic pathways but made human infection more likely (p < 0.05). Our findings provide new insights into aquatic ecological conservation and environmental management.

Nitrogen addition enhanced Per-fluoroalkyl substances' microbial availability in a wheat soil ecosystem.

Per-fluoroalkyl substances (PFASs) have been widely detected in farmland soils and are understood to pose toxicological threats to soil microbiomes and crop safety. Meanwhile, farmland ecosystems have experienced increasing nitrogen loading caused by soil fertilization. Yet it is still unclear how nitrogen additions affect soil's microbial responses to PFASs. In this study, using a laboratory-based ecological experiment, we assessed the microbial availability of PFASs in soils receiving ammonium, nitrate, and urea nitrogen amendments by quantifying the translocation factors of PFASs from soil particle to soil extracellular polymeric substances (EPS). Our results showed that nitrogen, specifically ammonium, significantly increased the PFASs' microbial availability (p < 0.05). Second, nitrogen fertilization in PFASs-polluted soils decreased the microbial community diversity and stability at the structural, species, and functional levels (p < 0.05). For soil microbial activities, nitrogen enhanced the activity of superoxide dismutase (SOD) while it inhibited the catalase (CAT) and peroxidase (POD) (p < 0.01). Congruently, PFASs, as well as the nitrate and nitrite nitrogen, were shown to be the predominant abiotic drivers regulating the soil fungal succession (p < 0.05), while bacteria were mostly regulated by dissolved organic carbon (DOC) (p < 0.01). Furthermore, we revealed that the nitrogen cycling gene hmp (dominates the transformation from NO to NO3-) was the hub gene integrating the microbially available PFASs and the soil nitrogen cycling processes (p < 0.01), indicating that hmp could be the core regulator affecting the accumulation of PFASs in soil EPS. Our study highlighted that decreasing ammonia's amendments could mitigate China's national initiatives to reduce nitrogen fertilization in farmlands, reduce the PFASs' availability to the soil microbiome, and protect the microbial community stability in soil.

Impacts of iron amendments and per-fluoroalkyl substances' bio-availability to the soil microbiome in wheat ecosystem.

Per-fluoroalkyl substances (PFASs) have become ubiquitous in farmland ecosystems and pose risks to agricultural safety, and iron is often applied to farmland soils to reduce the availability of pollutants. However, the effects of iron amendment on the availability of PFASs in the soil and on the soil microbiome are not well understood. Here, we investigated the responses of wheat soil containing PFASs to iron addition using a 21-day experiment. Our results showed that iron amendment enhanced PFAS availability (p < 0.05) and stimulated superoxide dismutase (SOD) activity in the wheat soil (p < 0.05), but iron amendment decreased the activities of soil catalase (CAT) and peroxidase (POD) (p < 0.05). Soil bacterial community was more structurally stable than fungal community in response to iron addition, while species' pools were more stable in fungi than in bacteria (p < 0.05). Finally, PFPeA's availability in the wheat soil was the most important abiotic factors driving community succession of iron-cycling bacteria (p < 0.05). These results highlighted the potential interactions among PFASs' availability and microbial iron cycling in wheat farmland soil ecosystems and provided guidance in farmland environmental conservation and management.

Removal of Per-, Poly-fluoroalkyl substances (PFASs) and multi-biosphere community dynamics in a bacteria-algae symbiotic aquatic ecosystem.

The presence of Per-, Poly-fluoroalkyl substances (PFASs) in aquatic ecosystems has drawn broad concerns in the scientific community due to their biological toxicity. However, little has been explored regarding PFASs' removal in phytoplankton-dominated environments. This study aimed to create a simulated bacteria-algae symbiotic ecosystem to observe the potential transportation of PFASs. Mass distributions showed that sand (63-2000 µm), silt & clay (0-63 µm), the phycosphere (>3 µm plankton), and the free-living biosphere (0.22-3 µm plankton) contained 19.00, 7.78, 5.73 and 2.75% PFASs in their total mass, respectively. Significant correlations were observed between carbon chain lengths and removal rates (R2 = 0.822, p < 10-4). Structural equation models revealed potential PFAS transportation pathways, such as water-phycosphere- free-living biosphere-sand-silt&clay, and water-sand-silt&clay (p < 0.05). The presence of PFASs decreased the bacterial density but increased algal density (p < 0.01) in the planktonic environment, and PFASs with longer carbon chain lengths showed a stronger enhancement in microbial community successions (p < 0.05). In algal metabolisms, chlorophyll-a and carotenoids were the key pigments that resisted reactive oxygen species caused by PFASs. PFBA (perfluorobutyric acid) (10.38-14.68%) and PFTeDA (perfluorotetradecanoic acid) (10.33-15.96%) affected bacterial metabolisms in phycosphere the most, while in the free-living biosphere was most effected by PFPeA (perfluorovaleric acid) (13.21-13.99%) and PFDoA (perfluorododecanoic acid) (10.04-10.50%). The results of this study provide new guidance measures for PFAS removal and management in aquatic environments.

Quinolone distribution, trophodynamics, and human exposure risk in a transit-station lake for water diversion in east China.

Quinolone antibiotics (QNs) pollution in lake environments is increasingly raising public concern due to their potential combined toxicity and associated risks. However, the spatiotemporal distribution and trophodynamics of QNs in transit-station lakes for water diversion are not well documented or understood. In this study, a comprehensive investigation of QNs in water, sediment, and aquatic fauna, including norfloxacin (NOR), ciprofloxacin (CIP), enrofloxacin (ENR), and ofloxacin (OFL), was conducted in Luoma Lake, a major transit station for the eastern route of the South-to-North Water Diversion Project in China. The target QNs were widely distributed in the water (∑QNs: 70.12 ± 62.79 ng/L) and sediment samples (∑QNs: 13.35 ± 10.78 ng/g dw) in both the non-diversion period (NDP) and the diversion period (DP), where NOR and ENR were predominant. All the QNs were detected in all biotic samples in DP (∑QNs: 80.04 ± 20.59 ng/g dw). The concentration of ∑QNs in the water in NDP was significantly higher than those in DP, whereas the concentration in the sediments in NDP was comparable to those in DP. ∑QNs in the water-sediment system exhibited decreasing trends from northwest (NW) to southeast (SE) in both periods; however, the Koc (organic carbon normalized partition coefficients) of individual QNs in DP sharply rose compared with those in NDP, which indicated that water diversion would alter the environmental fate of QNs in Luoma Lake. In DP, all QNs, excluding NOR, were all biodiluted across the food web; whereas their bioaccumulation potentials in the SE subregion were higher than those in the NW subregion, which was in contrast to the spatial distribution of their exposure concentrations. The estimated daily QN intakes via drinking water and aquatic products suggested that residents in the SE side were exposed to greater health risks, despite less aquatic pollution in the region.

Linking microbiomes with per- and poly-fluoroalkyl substances (PFASs) in soil ecosystems: Microbial community assembly, stability, and trophic phylosymbiosis.

Microbiomes are vital in promoting nutrient cycling and plant growth in soil ecosystems. However, microbiomes face adverse effects from multiple persistent pollutants, including per- and poly-fluoroalkyl substances (PFASs). PFASs threaten the fertility and health of soil ecosystems, yet the response of microbial community stability and trophic transfer efficiencies to PFASs is still poorly understood. This study explored the spatial patterns of PFASs in topsoil environments from the West Taihu Lake Basin of China and links their presence to soil microbial community stability at compositional and functional levels. Our results revealed that PFBA (13.87%), PFTrDA (11.63%), PFDoA (11.02%), PFOA (10.99%), and PFOS (10.39%) contributed the most to the spatial occurrence of PFASs. Soil properties, including salinity (14.47%), uniformity (9.68%), dissolved inorganic carbon (8.62%), and clay content (8.18%), affected PFASs distribution the most. In soil microbiomes, eukaryotic taxa had wider niche breadths and stronger community stability than prokaryotes when exposed to PFASs (p < 0.05). The presence of PFBA and PFHpA inhibited the functional stability of archaeal and bacterial communities (p < 0.05). PFBA and PFPeA reduced the structural stability of heterotrophic bacteria and Myxobacteria, respectively (p < 0.05). Based on null modeling, PFPeA significantly regulated the assembly processes of most microbial sub-communities (p < 0.01). The trophic transferring efficiencies of autotrophic bacteria to metazoan organisms were directly stimulated by PFASs (p < 0.05), and the potential trophic transferring efficiencies of methanogenic archaea to protozoa were inhibited by PFASs (p < 0.05). This study highlighted the potential contributions of PFASs to soil microbial community stability and food webs during ecological soil management.

Per-, poly-fluoroalkyl substances (PFASs) and planktonic microbiomes: Identification of biotic and abiotic regulations in community coalescence and food webs.

The importance of per-, poly-fluoroalkyl substances (PFASs) effects on riverine microbiomes is receiving increased recognition in the environmental sciences. However, few studies have explored how PFASs affect microbiomes across trophic levels, specifically through predator-prey interactions. This study examined the community profiles of planktonic archaea, bacteria, fungi, algae, protozoa, and metazoa in a semi-industrial and agricultural river alongside their interactions with 15 detected PFASs. As abiotic factors, PFASs affected community coalescence more than biogenic substances (p < 0.05). For biotic regulations, sub-communities in rare biospheres (including always rare taxa-ART and critically rare taxa-CRT) contributed to spatial community coalescence more than sub-communities in abundant biospheres (always abundant taxa-AAT and critically abundant taxa-CAT) (p < 0.05). Metazoa-bacteria (Modularity = 1.971) and protozoa-fungi (1.723) were determined to be the most stable predator-prey networks. Based on pathway models, short-chain PFBA (C4) was shown to weaken the trophic transfer efficiencies from heterotrophic bacteria (HB) to heterotrophic flagellates (HF) (p < 0.05). Long-chain PFTeDA (C14) promoted HB to amoeba (p < 0.05), which we postulate is the pathway for PFTeDA to enter the microbial food chain. Our preliminary results elucidated the influence of PFASs on planktonic microbial food webs and highlighted the need to consider protecting and remediating riverine ecosystems containing PFASs.

Shift in the distribution and fate of perfluoroalkyl acids by sluice gates in the multi-environment media of rivers.

The impact of sluice operations on the distribution and fate of perfluoroalkyl acids (PFAAs) remains poorly understood. In this study, the distribution of PFAAs was investigated in water, suspended particles, sediment, and pore water from the upstream and downstream sections of six sluice gates along the Wangyu River, China. The target PFAAs were widely distributed in the dissolved phase (∑PFAAs: 447.61 ± 180.26 ng/L), particle phase (∑PFAAs: 2040.95 ± 1870.88 ng/g dw), sedimentary phase (∑PFAAs: 39.42 ± 35.38 ng/g dw), and pore water phase (∑PFAAs: 8172.54 ± 4278.60 ng/L). Our data suggest predominant detections of short-chain PFAAs such as perfluorobutanoic acid (PFBA) and perfluorohexanoic acid (PFHxA) in the four environmental media. Sediment pore water appeared as an essential repository and potential source for PFAA re-release to the river environment. The levels of PFAAs in the dissolved and suspended particle phase upstream of the sluices were significantly lower than those downstream, while the situation in the sediment and pore water phase was the opposite. Sluice operation caused PFAA redistribution among the multi-environment media but did not change the PFAA composition, which had the significant effect on the partition behavior of perfluoroalkyl carboxylic acids (PFCAs) between particles and water, as well as changed the migration pattern of PFOA, PFNA and PFOS from equilibrium to the migration state. Quantitative prediction models were developed for simulating fate of PFAAs in gate-controlled river, and the major factors affecting the distribution and fate of PFAAs were identified. Our findings provide insights into the redistribution mechanisms of PFAAs and an understanding of their environmental fate.

Perfluorinated compounds (PFCs) in regional industrial rivers: Interactions between pollution flux and eukaryotic community phylosymbiosis.

Perfluorinated compounds (PFCs) pose serious threats to aquatic ecosystems, especially their microbial communities. However, little is known about the phylosymbiosis of aquatic fungal and viridiplantae communities in response to PFC accumulation. We quantified the distribution of 14 PFCs in rivers and found that PFBA was dominant in the transition from water to sediment. High through-put sequencing revealed that phyla Ascomycota, Basidiomycota, Anthophyta, and Chlorophyta were the predominant in eukaryotic community. The effects of PFCs on spatial community coalescence at taxonomic and phylogenetic levels (p < 0.05) were revealed. Fungal community coalescence triggered the spatial assembly of fungal and viridiplantae communities in riverine environments (p < 0.05). Null modeling indicated that PFBA, PFTrDA and PFOS, etc, mediated phylogenetic assembly (p < 0.05) and stochastic processes (86.67-100%) maintain phylogenetic turnover in the fungal community. Meanwhile, variable selection (27.78-54.44%) explained the viridiplantae community assemblage. Finally, we identified fungal genera Hannaella, Naganishia, Purpureocillium and Stachybotrys as indicators for PFC pollution (p < 0.001). These results help explain the effects of PFCs on riverine ecological remediation.

Prognostic impact of lymph node harvest for patients with node-negative esophageal squamous cell carcinoma: a large-scale multicenter study.

BACKGROUND: We examined the association between the number of resected lymph nodes and survival to determine the optimal lymphadenectomy for thoracic esophageal squamous cell carcinoma (ESCC) patients with negative lymph node. METHODS: We included 1,836 patients from Chinese three high-volumed hospitals with corresponding clinicopathological characters such as gender, age, tumor location, tumor grade and TNM stage of patients. The median follow-up of included patients was 45.7 months (range, 1.03-117.3 months). X-Tile plot was used to identify the lowest number of lymphadenectomy. The multivariate model's construction was in use of parameters with clinical significance for survival and a nomogram based on clinical variable with P<0.05 in Cox regression analysis. Both two models were validated using a cohort extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database between 1975 and 2016 (n=951). RESULTS: More lymphadenectomy numbers were significantly associated with better survival in patients both in training cohort [hazard ratio (HR) =0.980; 95% confidence interval (CI): 0.971-0.988; P<0.001] and validation cohort (HR =0.980; 95% CI: 0.968-0.991; P=0.001). Cut-off point analysis determined the lowest number of 9 for thoracic ESCC patients in N0 stage through training cohort (C-index: 0.623; sensitivity: 80.7%; 1 - specificity: 72.5%) when compared with 10 in validation cohort (C-index: 0.643; sensitivity: 78.2%; 1 - specificity: 63.0%). The cut-off points of 9 were examined in training cohort and validated in the divided cohort from validation cohort (all P<0.05). Meanwhile, nomograms for both cohorts were constructed and the calibration curves for both cohorts agreed well with the actual observations in terms of predicting 3- and 5-year survival, respectively. CONCLUSIONS: Larger number for lymphadenectomy was associated with better survival in thoracic ESCC patients in N0 stage. Nine was what we got as the lowest number for lymphadenectomy in pN0 ESCC patients through this study, and our result should be confirmed further.

P300/CBP-associated factor (PCAF)-mediated acetylation of Fascin at lysine 471 inhibits its actin-bundling activity and tumor metastasis in esophageal cancer.

BACKGROUND: Fascin is crucial for cancer cell filopodium formation and tumor metastasis, and is functionally regulated by post-translational modifications. However, whether and how Fascin is regulated by acetylation remains unclear. This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis. METHODS: Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor (PCAF), and immunofluorescence was used to investigate their colocalization. An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry. A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma (ESCC) cells using Western blotting by overexpressing and knocking down PCAF expression. An in vitro cell migration assay was performed, and a xenograft model was established to study in vivo tumor metastasis. Live-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation. The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry. RESULTS: Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471 (K471) by PCAF. Using the specific anti-AcK471-Fascin antibody, Fascin was found to be acetylated in ESCC cells, and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown. Functionally, Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis, whereas Fascin-K471 deacetylation exhibited a potent oncogenic function. Moreover, Fascin-K471 acetylation reduced filopodial length and density, and lifespan of ESCC cells, while its deacetylation produced the opposite effect. In the filipodium shaft, K471-acetylated Fascin displayed rapid dynamic exchange, suggesting that it remained in its monomeric form owing to its weakened actin-bundling activity. Clinically, high levels of AcK471-Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease-free survival of ESCC patients. CONCLUSIONS: Fascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells. Fascin-K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin-bundling activity.

Per-, poly-fluoroalkyl substances (PFASs) pollution in benthic riverine ecosystem: Integrating microbial community coalescence and biogeochemistry with sediment distribution.

Per-, Poly-fluoroalkyl substances (PFASs) accumulation in benthic environments is mainly determined by material mixing and represents a significant challenge to river remediation. However, less attention has been paid to the effects of sediment distribution on PFASs accumulation, and how PFASs influence microbial community coalescence and biogeochemical processes. In order to identify correlations between PFASs distribution and benthic microbial community functions, we conducted a field study and quantified the ecological constrains of material transportation on benthic microorganisms. Perfluorohexanoic acid (PFHxA) contributed most to the taxonomic heterogeneity of both archaeal (12.199%) and bacterial (13.675%) communities. Genera Methanoregula (R2 = 0.292) and Bacillus (R2 = 0.791) were identified as indicators that respond to PFASs. Phylogenetic null modeling indicated that deterministic processes (50.0-82.2%) dominated in spatial assembly of archaea, while stochasticity (94.4-97.8%) dominated in bacteria. Furthermore, spatial mixing of PFASs influenced broadly in nitrogen cycling of archaeal genomes, and phosphorus mineralization of bacterial genomes (p < 0.05). Overall, we quantified the effect of PFASs on community assembly and highlighted the constrains of PFASs influence on benthic geochemical potentials, which may provide new insights into riverine remediation.

Planktonic microbial responses to perfluorinated compound (PFC) pollution: Integrating PFC distributions with community coalescence and metabolism.

The presence of perfluorinated compound (PFC) contamination in riverine ecosystems represents a novel challenge for environmental remediation. However, little attention has been paid to how PFCs affect planktonic microbial community coalescence. Here, the spatial profiles of fourteen PFCs and their contributions to community assembly were determined using field sampling in a natural river confluence. Overall, PFPeA (perfluorovaleric acid), PFBS (perfluorobutylsulfonate), PFHpA (perfluoroheptanoic acid) and PFHxA (perfluorohexanoic acid) were identified as important indicators of PFC pollution, accounting for the majority of the spatial heterogeneity in PFC pollution. PFPeA (perfluorovaleric acid) (9.39%) and PFTrDA (perfluorotridecanoate acid) (8.61%) contributed more to microbial taxonomic spatial heterogeneity than did other factors, such as pH, dissolved oxygen and velocity. PFOA (pentadecafluorooctanoic acid) (R2 = 0.353) and PFBS (R2 = 0.297) drove turnover in archaeal communities within river sections (transversely), while PFHpA (R2 = 0.251) and PFOS (perfluorooctane sulphonate) (R2 = 0.105) drove turnover in bacterial communities transversely and longitudinally, respectively. Phylogenetic null modeling suggested that archaeal (68.89-83.33%) community assembly was dominated by stochastic processes, and was balanced by PFHxA (R2 = 0.349) and PFOA (R2 = 0.290). Furthermore, PFOS inhibited the biosynthesis of several key amino acids in archaea, and PFBA enhanced the potential for bacterial infections in humans (p < 0.05), threatening water quality. In sum, this study provides new insights into riverine ecological risk management.

Removal of perfluoroalkyl acids (PFAAs) in constructed wetlands: Considerable contributions of submerged macrophytes and the microbial community.

The broad application of perfluoroalkyl acids (PFAAs) has attracted global concern regarding their adverse environmental effects. The possible removal processes of PFAAs in constructed wetlands were excavated and quantified using two typical submerged macrophytes (rooted Potamogeton wrightii and rootless Ceratophyllum demersum). Our results showed that 33.59-88.99% of PFAAs could be removed via not only sediment sorption or phytoextraction but also by the bioaccumulation of microbiota. The sediment acts as a vital sink for PFAAs, preloading 23.51-50.09% and 16.65-52.18% of PFAAs in treatments with P. wrightii (Pw1) and C. demersum (Cd1), respectively. C. demersum showed a better capacity to accumulate PFAAs (0.91-32.03%) than P. wrightii (<10%). Considerable PFAAs were observed to be distributed in microbes, underlining the non-negligible role of microbiota in bioaccumulating PFAAs. The contributions of planktonic microbes, biofilm microbes, and extracellular polymeric substances in biofilms were 0.39-20.96%, 0.03-7.95%, and 0.39-14.15% in Pw1 and 0.23-15.68%, 0.01-15.68%, and 0.53-26.77% in Cd1, respectively. The adsorption/uptake was significantly correlated with the perfluoroalkyl chain length (p<0.05), except for the uptake of biofilms in C. demersum. Furthermore, PFAAs and submerged macrophytes could decrease the richness of microbiota but increase the relative abundance of some strains in Betaproteobacteriales, Sphingomonadales, and Cytophagales. Our results were helpful for understanding the removal processes of PFAAs in constructed wetlands and their linkages with PFAA properties, thus further providing insight into the management and removal of emerging organic contaminants.

Prognostic Role of Nodal Skip Metastasis in Thoracic Esophageal Squamous Cell Carcinoma: A Large-Scale Multicenter Study.

BACKGROUND: Nodal-skip metastasis (NSM) is found in esophageal squamous cell carcinoma (ESCC), but its prognostic role is controversial. This study aimed to investigate the prognostic value of NSM for thoracic ESCC patients. METHODS: Categorization of NSM was according to the N groupings of Japan Esophagus Society (JES) staging system, which is dependent on tumor location. Using the Kaplan-Meier method and Cox-regression analysis, this study retrospectively analyzed the overall survival (OS) for 2325 ESCC patients after radical esophagectomy at three high-volume esophageal cancer centers. Predictive models also were constructed. RESULTS: The overall NSM rate was 20% (229/1141): 37.4% in the in upper, 12.9% in the middle, and 22.2% in the lower thoracic ESCC. The patients with NSM always had a better prognosis than those without NSM. Furthermore, NSM was an independent prognostic factor for thoracic ESCC patients (hazard ratio [HR], 0.633; 95% confidence interval [CI], 0.499-0.803; P < 0.001). By integrating the prognostic values of NSM and N stage, the authors proposed the new N staging system. The categories defined by the new N staging system were more homogeneous in terms of OS than those defined by the current N system. Moreover, the new N system was shown to be an independent prognostic factor also for thoracic ESCC patients (HR, 1.607; 95% CI, 1.520-1.700; P < 0.001). Overall, the new N system had slightly better homogeneity, discriminatory ability, and monotonicity of gradient than the current N system. CONCLUSIONS: This study emphasized the prognostic power of NSM and developed a modified node-staging system to improve the efficiency of the current International Union for Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) N staging system.

Benthic prokaryotic microbial community assembly and biogeochemical potentials in E. coli - Stressed aquatic ecosystems during plant decomposition.

Benthic microbes play a crucial role in maintaining the biogeochemical balance of aquatic ecosystems especially the material cycling during plant decomposition. However, those systems in agricultural area are always threatened by agricultural run-off containing a mass of typical pathogenic invader- Escherichia coli. It is therefore vital to clarify the turnover, assembly, and geochemical functions of the E. coli invaded benthic prokaryotic microbial community during plant decomposition. During the decaying process, the key filtering factors of benthic community assembly were NH4+-N (P < 0.001), NO2--N (P < 0.01), and Organic-N (P < 0.05). The E. coli colonized significantly in sediments (P < 0.001) and drove the turnover of the bacterial community (P = 0.001), which enhanced archaeal dominance in the benthic microbial network. E. coli also triggered niche structural variations. The biomass (%) of benthic nutrient cycling genera including Dechloromonas, Pseudomonas, Bacteroides, Candidatus_Methanofastidiosum, and Desulfomicrobium (P < 0.05) was altered by E. coli stress. The structural equation model illustrated that E. coli critically affected the benthic microbial geochemical functions in multiple pathways (P < 0.05). Our results provide new insights into benthic prokaryotic microbial community assembly and nutrient cycling and management under pollution stress.

Systematic Proteome and Lysine Succinylome Analysis Reveals Enhanced Cell Migration by Hyposuccinylation in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor therapeutic outcomes. However, the alterations in proteins and posttranslational modifications (PTMs) leading to the pathogenesis of ESCC remain unclear. Here, we provide the comprehensive characterization of the proteome, phosphorylome, lysine acetylome, and succinylome for ESCC and matched control cells using quantitative proteomic approach. We identify abnormal protein and PTM pathways, including significantly downregulated lysine succinylation sites in cancer cells. Focusing on hyposuccinylation, we reveal that this altered PTM was enriched on enzymes of metabolic pathways inextricably linked with cancer metabolism. Importantly, ESCC malignant behaviors such as cell migration are inhibited once the level of succinylation was restored in vitro or in vivo. This effect was further verified by mutations to disrupt succinylation sites in candidate proteins. Meanwhile, we found that succinylation has a negative regulatory effect on histone methylation to promote cancer migration. Finally, hyposuccinylation is confirmed in primary ESCC specimens. Our findings together demonstrate that lysine succinylation may alter ESCC metabolism and migration, providing new insights into the functional significance of PTM in cancer biology.