Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9

BackgroundDespite advances in anastomotic techniques and perioperative care, the incidence of anastomotic leak (AL) has not substantially decreased over time. Although it is known that AL etiology is multifactorial and the mechanisms involved remain unclear, there is accumulating evidence pointing at AL related to gut microbiota.MethodWe firstly performed a clinical study to analyze the gut microbiota between colorectal cancer patients who developed AL and those who did not (nAL) using 16S-rRNA sequencing and quantitative real-time PCR to identify AL risk bacterial taxa. Then we built a rat anastomosis model and performed a bacteria transplantation to ensure the cause-effect relationship. The anastomotic healing score was used to evaluate the healing of anastomosis. In addition, we assessed the adhesion ability of bacteria by staining with fluorescein isothiocyanate and attachment assay. The expression of matrix metalloproteinase 9 (MMP9) was detected by western blot, and the activity was detected by gelatin zymography.ResultsWe found that the abundance and positive rate of Fusobacterium nucleatum (Fn) were higher in the AL patients. Exposure of the rat’s colon anastomosis to Fn contributes to the loss of submucosa collagen I and III, leading to AL’s pathogenesis. Fn can attach to the gut epithelial cells and stimulate intestinal MMP9 expression in vitro and in vivo. We further confirmed that these effects of Fn depended on the E-cadherin/β-catenin signaling pathway.ConclusionThis work demonstrates that Fn attaches and then stimulates the expression of epithelial cells MMP9 by the E-cadherin/β-catenin signaling pathway. These effects contribute to collagen break down in the intestinal tissue, finally leading to AL

Pressure-stabilized divalent ozonide CaO3 and its impact on Earth's oxygen cycles.

High pressure can drastically alter chemical bonding and produce exotic compounds that defy conventional wisdom. Especially significant are compounds pertaining to oxygen cycles inside Earth, which hold key to understanding major geological events that impact the environment essential to life on Earth. Here we report the discovery of pressure-stabilized divalent ozonide CaO3 crystal that exhibits intriguing bonding and oxidation states with profound geological implications. Our computational study identifies a crystalline phase of CaO3 by reaction of CaO and O2 at high pressure and high temperature conditions; ensuing experiments synthesize this rare compound under compression in a diamond anvil cell with laser heating. High-pressure x-ray diffraction data show that CaO3 crystal forms at 35 GPa and persists down to 20 GPa on decompression. Analysis of charge states reveals a formal oxidation state of -2 for ozone anions in CaO3. These findings unravel the ozonide chemistry at high pressure and offer insights for elucidating prominent seismic anomalies and oxygen cycles in Earth's interior. We further predict multiple reactions producing CaO3 by geologically abundant mineral precursors at various depths in Earth's mantle

The combined signatures of telomere and immune cell landscape provide a prognostic and therapeutic biomarker in glioma

BackgroundGliomas, the most prevalent primary malignant tumors of the central nervous system in adults, exhibit slow growth in lower-grade gliomas (LGG). However, the majority of LGG cases progress to high-grade gliomas, posing challenges for prognostication. The tumor microenvironment (TME), characterized by telomere-related genes and immune cell infiltration, strongly influences glioma growth and therapeutic response. Therefore, our objective was to develop a Telomere-TME (TM-TME) classifier that integrates telomere-related genes and immune cell landscape to assess prognosis and therapeutic response in glioma.MethodsThis study encompassed LGG patients from the TCGA and CCGA databases. TM score and TME score were derived from the expression signatures of telomere-related genes and the presence of immune cells in LGG, respectively. The TM-TME classifier was established by combining TM and TME scores to effectively predict prognosis. Subsequently, we conducted Kaplan-Meier survival estimation, univariate Cox regression analysis, and receiver operating characteristic curves to validate the prognostic prediction capacity of the TM-TME classifier across multiple cohorts. Gene Ontology (GO) analysis, biological processes, and proteomaps were performed to annotate the functional aspects of each subgroup and visualize the cellular signaling pathways.ResultsThe TM_low+TME_high subgroup exhibited superior prognosis and therapeutic response compared to other subgroups (P<0.001). This finding could be attributed to distinct tumor somatic mutations and cancer cellular signaling pathways. GO analysis indicated that the TM_low+TME_high subgroup is associated with the neuronal system and modulation of chemical synaptic transmission. Conversely, the TM_high+TME_low subgroup showed a strong association with cell cycle and DNA metabolic processes. Furthermore, the classifier significantly differentiated overall survival in the TCGA LGG cohort and served as an independent prognostic factor for LGG patients in both the TCGA cohort (P<0.001) and the CGGA cohort (P<0.001).ConclusionOverall, our findings underscore the significance of the TM-TME classifier in predicting prognosis and immune therapeutic response in glioma, shedding light on the complex immune landscape within each subgroup. Additionally, our results suggest the potential of integrating risk stratification with precision therapy for LGG

Long-term trends and extreme events of marine heatwaves in the Eastern China Marginal Seas during summer

Marine heatwaves (MHWs) are a type of widespread, persistent, and extreme marine warming event that can cause serious harm to the global marine ecology and economy. This study provides a systematic analysis of the long-term trends of MHWs in the Eastern China Marginal Seas (ECMS) during summer spanning from 1982 to 2022, and occurrence mechanisms of extreme MHW events. The findings show that in the context of global warming, the frequency of summer MHWs in the ECMS has increased across most regions, with a higher rate along the coast of China. Areas exhibiting a rapid surge in duration predominantly reside in the southern Yellow Sea (SYS) and southern East China Sea (ECS, south of 28°N). In contrast, the long-term trends of mean and maximum intensities exhibit both increases and decreases: Rising trends primarily occur in the Bohai Sea (BS) and Yellow Sea (YS), whereas descending trends are detected in the northern ECS (north of 28°N). Influenced jointly by duration and mean intensity, cumulative intensity (CumInt) exhibits a notable positive growth off the Yangtze River Estuary, in the SYS and southern ECS. By employing the empirical orthogonal function, the spatio-temporal features of the first two modes of CumInt and their correlation with summer mean sea surface temperature (SST) and SST variance are further examined. The first mode of CumInt displays a positive anomalous pattern throughout the ECMS, with notable upward trend in the corresponding time series, and the rising trend is primarily influenced by summer mean SST warming. Moreover, both of the first two modes show notable interannual variability. Extreme MHW events in the SYS in 2016 and 2018 are examined using the mixed layer temperature equation. The results suggest that these extreme MHW events originate primarily from anomalous atmospheric forcing and oceanic vertical mixing. These processes involve an anomalous high-pressure system over the SYS splitting from the western Pacific subtropical high, augmented atmospheric stability, diminished wind speeds, intensified solar radiation, and reduced oceanic mixing, thereby leading to the accumulation of more heat near the sea surface and forming extreme MHW events

Characteristics and mechanism of winter marine heatwaves in the cold tongue region of the South China Sea

Marine Heatwaves (MHWs) are persistent anomalous sea surface temperature warming events that can affect the marine ecological environment and ecosystems. Here, we study the winter MHWs in the cold tongue region of the South China Sea (SCS) from 1982 to 2022. Our results show that the winter MHWs in the cold tongue region have the strongest cumulative intensity in the SCS, exceeding 45°C·day/time. These strong MHWs are due to their high mean intensity and long duration. Significant interannual variations are observed in these MHWs, with extreme MHW events occurring in the El Niño winters of 97/98 and 15/16. By employing a mixed layer heat budget analysis, we reveal that the extreme MHW event in the winter of 97/98 is caused primarily by the surface heat flux term, and secondarily by the vertical entrainment term. While the 15/16 extreme event is caused by a combination of the surface heat flux term, the vertical entrainment term and the horizontal advection term

Key role of subdaily wind variability for tropical surface wind stress

High-frequency observations of surface winds over the open ocean are available only at limited locations. However, these observations are essential for assessing atmospheric influences on the ocean, validating reanalysis products, and building parameterization schemes. By analyzing high-frequency measurements from the Global Tropical Moored Buoy Array, the effects of subdaily winds on the mean surface wind stress magnitude are systematically examined. Subdaily winds account for 12.4% of the total stress magnitude on average. The contribution is enhanced over the Intertropical Convergence Zone and reaches a maximum (28.5%) in the equatorial western Pacific. The magnitude of the contribution is primarily determined by the kinetic energy of subdaily winds. Compared to the buoy observations, the ERA5 and MERRA2 subdaily winds underestimate this contribution by 51% and 63% due to underestimations of subdaily kinetic energy, leading to 7% and 8% underestimations in the total stress magnitude, respectively. Two new gustiness parameterization schemes related to precipitation are developed to account for the effect of subdaily winds, explaining ~80% of the contribution from subdaily winds. Considering the importance of wind stress for ocean-atmosphere interactions, the inclusion of these parametrization schemes in climate models is expected to substantially improve simulations of large-scale climate variability

Analysis of Traffic Capacity on Mountainous Two Lane Highway Adding Climbing Lane

During the construction of mountainous double lane highway, climbing lane plays a certain role for enhancing the traffic capacity. In order to explore traffic capacity improvement effect for different conditions of climbing lane, 20 representative models are chosen, which contain various combinations of alignment and traffic parameters. The changes of traffic capacity, average speed, delays, and saturation in models are obtained before and after the use of a climbing lane by means of numerical simulation. The results show that the use of a climbing lane could improve traffic capacity, average speed, while reducing delays and saturation. The improvement effect is different according to different combinations of alignment and traffic parameters. The research could provide a reference for mountainous climbing lane construction intend