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The main focus of studying sediment sources in marine areas is to determine the properties of clastic minerals originating from different rivers. Variations in the characteristics of clastic minerals occur due to differences in the types of source rocks within the watershed. Determining the source rock of clastic minerals in the marine area can improve the accuracy of provenance analysis. Electron probe microanalysis of 258 amphibole grains from six surface stations in the South Yellow Sea (SYS) was conducted to calculate the numerical and characteristic values of cations in the crystal structure. The results showed that amphibole in the SYS is mainly magnesiohornblende (52.2% ~ 81.4%) in the calcic amphibole subgroup, followed by tschermakite. The source rock types of amphibole are mainly different types of magmatic (ultrabasic, basic, and intermediate acidic) and metamorphic rocks. Amphibole derived from intermediate-acid intrusive rocks accounts for a large proportion (>40%). The genetic analysis of clastic amphibole in the SYS showed that most of the medium-acid invading amphibole belong to crust-mantle type, followed by mantle type. Most of the amphibole from metamorphic origins are of medium-low pressure type (± 80%). Combined with electron probe analysis of amphibole from the Huanghe River (the Yellow River, HH) and Changjiang River (the Yangtze River, CJ), the amphibole in the SYS exhibits characteristics inherited from these two rivers. The northern sea area has a strong resemblance to the sediments from the HH, while the southern area is more influenced by sediments supply from the CJ. The central area represents a mixed zone with a higher sediment supply from the HH. The clastic amphibole deduces the type of source rock in different watersheds, serving as a crucial link between the source rock, watershed, and marine area, providing a basis for provenance analysis.

Typhoon-induced storms surges and river flooding events represent two types of natural disasters that affect a wide range, occurring with high frequency and causing serious societal losses. Due to the limited duration of instrumental records, there is an inadequate understanding of the patterns and mechanisms underlying the variations in typhoons and floods. The interpretation of sedimentary records aptly compensates for these deficiencies in terms of the temporal scale, becoming a crucial medium for extending the temporal span of typhoon and flood records. Previous studies in this field have primarily focused on the identification of single types of extreme events. The Changjiang Estuary, particularly Chongming Island, is significantly affected by both typhoons and river floods, making it an excellent area for synchronous comparative studies of these two types of extreme events. Based on the analysis of a core sample, ZP02, collected from Chongming Island, in terms of chronological, sedimentological, and geochemical characteristics, specific tracing fingerprints for event deposits from typhoon and flood events are established. Sediments from typhoon events generally exhibit erosive contact surfaces, coarser grain sizes, and a tendency to become finer upwards, often featuring layers mixed with coarse sand and shell fragments. In contrast, flood event deposits vary in grain size, either coarser or finer, with abrupt contact surfaces compared to normal sediment layers, and are predominantly brownish-yellow in color. The fingerprint tracing results indicate that the typhoon event layers are characterized by high values in principal component 2 (PC2) of the elements, Zr/Fe and Sr/Fe ratios, with low values in principal component 1 (PC1) the elements and Ti/Ca ratio. Flood event deposits are marked by high values in PC1 and Ti/Ca ratio, low values in PC2 and Sr/Fe ratio, and an increase in Zr/Fe ratio in coarser flood layers but no significant change in finer layers. Based on these fingerprints, 19 layers of typhoon and the same number of flood events were identified in core ZP02, which correspond well with documentary records. The establishment of tracing fingerprints for typhoon and flood event deposits provides methodological support for the identification and interpretation of various extreme event deposits.

With sea level rise (SLR), tidal nuisance flooding has become a growing threat, especially around estuaries with large tidal amplitudes. This study investigated how sea level change affects tides in Hangzhou Bay, a macro-tidal estuary with high SLR rate. By downscaling climate projections to a regional hydrodynamic model, the amplitude of primary tidal constituent (M2) was predicted to increase by 0.25 m in the upper bay, where the amplitude of major diurnal tide (K1) was also predicted to increase by 15%. In addition, the sensitivity of tidal amplitude to mean sea level was examined by a set of numerical simulations with different SLR. It was found that the increase of tidal amplitude is nonlinear to SLR, and the tidal amplitudes almost cease to increase when SLR is over 1.5 m. Although predictions show less amplitude changes in the lower bay, Zhoushan Archipelago around the bay mouth strongly modulates the incoming tidal energy, thus affecting the tidal amplitude in the upper bay. Energy budget analysis revealed that the complex topography, such as narrow channels, in the archipelago area leads to strong horizontal shear, which dissipates approximately 25% of total tidal energy in the bay. On the other hand, around 60% of the energy is dissipated in the bottom boundary layer. However, the bottom dissipation decreases by 4% due to reduced friction, while horizontal dissipation increases by 10% due to enhanced horizontal shear with SLR. This suggests that the strong horizontal shear in the Zhoushan archipelago region can play a more important role in the tidal energy budget in the future.

Natural processes and anthropogenic activities are vital in dictating the amount and character of organic carbon (OC) input into large river deltas and adjacent shelves. Previous studies have indicated that sediment from the Huanghe River (HR) has significantly affected the formation of the northern Yangtze River subaqueous delta (YRD) over the past several hundred years. However, whether this process has changed sedimentary OC burial in the YRD remains unclear. A sediment core was collected from the YRD in 2018 CE for optically stimulated luminescence and 210Pb dating as well as grain size, total OC, total nitrogen, and stable-isotope analyses to investigate temporal changes in sedimentary OC over the past 2000 years. The results indicate that changes in terrestrial OC inputs to the YRD have been controlled mainly by the East Asian summer monsoon and anthropogenic influences in the past 2000 years. However, the decreased terrestrial OC inputs after 1385 CE, have been significantly affected by increased contribution of HR sediment to the YRD when the HR lower courses shifted to enter the southern Yellow Sea. This study demonstrates that sediment source changes should not be neglected in analyses of mechanisms and variations in OC burial in estuarine and coastal areas.

The southern coast of Hainan Island, China, is one of the most frequently hit areas of tropical cyclones in the Northwest Pacific regions. Although some of the extreme typhoon events were known in historical times, quantitative information on the timing and magnitude of paleo-typhoon events in this coastal area remains rare. In the present study, a large number of coral reef boulders were found on the Xiaodonghai reef platform, on the south coast of Hainan Island. Morphometric analysis of the boulders shows an exponentially fining landward trend, indicating a storm origin; a wave-induced current velocity of 2.41–5.71 m/s during the storm events is required to transport the boulders that were originally situated outside the reef edge. Based on the U/Th and 14C dating for the age-indicating samples taken from the boulders, seven major periods with intense typhoon activities were identified for the last 4,000 years, i.e., 1800–1500 BCE, 1200–900 BCE, 50–120 CE, 550–800 CE, 900–1000 CE, 1350–1900 CE, and 1910–2000 CE. A comparison with the regional typhoon records in terms of climatic parameters in the northwestern Pacific and the South China Sea regions indicates that the longitudinal variations of intense typhoon frequency were mainly controlled by El Niño-Southern Oscillation (ENSO), dominantly modulated by the Intertropical Convergence Zone. Because of the future warming climate, there will be a trend of enhanced typhoon risk for the southern Hainan Island coasts.

Humans have been sailing across seas and oceans for thousands of years. However, the story of large ships capable of affecting coastal ecology and shelf sedimentary processes is only about 100 years old. Modern large seagoing vessels with a draft of 10–20 m can cause resuspension of seabed sediment, erosion of the channel slope and shoal, enhancement of seafloor sediment activity and thickening of the active layer, thereby having a significant impact on seabed topography and sedimentation processes. However, little is known about the effects of this anthropogenic agent on shelf sedimentation due to limited observational data. Here, two sediment cores were collected from a shipping lane used by vessels of 5,000- to 50,000-ton off the coast of China to analyze their sedimentary properties, with focus on both the grain size and elements. It was found that ship disturbance selectively modified the sedimentary record, with the fine-grained sediment becoming increasingly unstable. In addition, there was a reduction in grain size of sediment finer than 6.25 Φ, which decreased by 11% after the disturbance by ship. Biogenic elements that were closely related to the ecological environment were significantly altered, with Br/Cl, Si/Ti, and Ca/Ti ratios all becoming significantly smaller. This indicated that frequent disturbance caused by ships had reduced the productivity in the waters near the shipping lane. In terms of sensitivity to the effects of ship navigation, the sedimentation response was relatively rapid and began to emerge from the commencement of ship navigation, whereas the ecological response became evident later than the sedimentation response and only appeared after a significant growth in the maritime transportation of China. Following the comparison of the two sediment cores, we propose that the constant rate of supply (CRS- with ship disturbance)–constant initial concentration (CIC- without ship disturbance) dual dating model be used to establish a dating framework in waters frequently disturbed by ship. This type of anthropogenic sedimentary dynamic process and its sedimentary–ecological effects deserve attention on this era where there is a surge in shipping globally. Shipping lanes present an excellent area for quantitative studies on the impacts of human activity and defining the Anthropocene in the context of shipping.

Object-location memory is particularly fragile and specifically impaired in Alzheimer’s disease (AD) patients. Electroencephalogram (EEG) was utilized to objectively measure memory impairment for memory formation correlates of EEG oscillatory activities. We aimed to construct an object-location memory paradigm and explore EEG signs of it. Two groups of 20 probable mild AD patients and 19 healthy older adults were included in a cross-sectional analysis. All subjects took an object-location memory task. EEG recordings performed during object-location memory tasks were compared between the two groups in the two EEG parameters (spectral parameters and phase synchronization). The memory performance of AD patients was worse than that of healthy elderly adults The power of object-location memory of the AD group was significantly higher than the NC group (healthy elderly adults) in the alpha band in the encoding session, and alpha and theta bands in the retrieval session. The channels-pairs the phase lag index value of object-location memory in the AD group was clearly higher than the NC group in the delta, theta, and alpha bands in encoding sessions and delta and theta bands in retrieval sessions. The results provide support for the hypothesis that the AD patients may use compensation mechanisms to remember the items and episode.

Myocardial ischemia-reperfusion injury (MIRI) is a significant factor in the development of cardiac dysfunction following a myocardial infarction. Ferroptosis, a type of regulated cell death driven by iron and marked by lipid peroxidation, has garnered growing interest for its crucial involvement in the pathogenesis of MIRI.This review comprehensively examines the mechanisms of ferroptosis, focusing on its regulation through iron metabolism, lipid peroxidation, VDAC signaling, and antioxidant system dysregulation. We also compare ferroptosis with other forms of cell death to highlight its distinct characteristics. Furthermore, the involvement of ferroptosis in MIRI is examined with a focus on recent discoveries concerning ROS generation, mitochondrial impairment, autophagic processes, ER stress, and non-coding RNA regulation. Lastly, emerging therapeutic strategies that inhibit ferroptosis to mitigate MIRI are reviewed, providing new insights into potential clinical applications.

This study marks the first occasion that Streptococcus iniae has been isolated, identified, and characterized as the causative pathogen in spotted sea bass (Lateolabrax maculates). Infected fish exhibited a range of external symptoms, including scale loss, bleeding from the jaw, anus, and tail, among other signs, as well as internal manifestations such as congested liver, splenomegaly, branchial anemia, yellow fat syndrome, and intestinal edema. Notably, exophthalmia and meningoencephalitis—typical symptoms associated with previous S. iniae infections—were not observed. A predominant bacterial isolate (designated 10S01) was recovered from the pure culture of spleen of a diseased spotted sea bass in Zhuhai, China. The strain was then subjected to Gram staining, biochemical profiling, and molecular confirmation through 16S rRNA and gyrB gene, corroborating its identity as S. iniae. Pathogenicity was assessed by intraperitoneal injection challenge in spotted sea bass weighing approximately 13 g/fish, revealing a LD50 of 74 cfu/g-fish. The 10S01 strain demonstrated the ability to colonize various organs, including the spleen, liver, kidney, and brain, with a relatively higher affinity for the spleen. Furthermore, antimicrobial susceptibility testing indicated that the 10S01 strain was sensitive to 14 tested antibiotics, particularly chloramphenicol, ciprofloxacin, clarithromycin, florfenicol, ofloxacin, rifampicin, and trimethoprim/sulfamethoxazole, highlighting these as preferred treatments for S. iniae infections in spotted sea bass. These findings contribute significantly to our understanding of S. iniae pathogenesis and inform the prompt and appropriate antibiotic treatment of S. iniae infections.

In recent years, significant advancements have been made in endovascular therapy for aortic dissection, resulting in the development of various treatment methods. Nevertheless, there is a contentious discussion regarding the suitability of different treatment methods for addressing the unique features of individual lesions. Specifically, the matter of whether the presence of small intimal tears or multiple distal tears requires extensive aortic coverage with graft stents, which may block the blood supply to important organs, intercostal arteries, or lumbar arteries, remains unresolved. Further research is necessary to determine the need for complex fenestrated or branched endovascular aortic repair (F/B-EVAR) in the management of chronic post-dissection aneurysms involving visceral arteries. Our report highlights the successful endovascular repair of three patients with aortic dissection, encompassing one Stanford A type and two Stanford B types. Utilizing the Amplatzer Vascular Plug (AVP) alone or in combination with the coil embolization technique, we achieved favorable clinical outcomes. This article aims to provide valuable insights and new perspectives on the tailored management of aortic dissection by conducting a comprehensive examination of the subtle differences in the treatment processes and techniques applied to these three patients.

ObjectiveTo evaluate the incidence and trend of catastrophic health expenditures (CHE) in China over the past 20 years and explore the socioeconomic factors affecting China's CHE rate.MethodsThe systematic review was conducted according to the Cochrane Handbook and reported according to PRISMA. We searched English and Chinese literature databases, including PubMed, EMbase, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang, China Science and Technology Journal Database (CQVIP), and CBM (Sino Med), for empirical studies on the CHE rate in China and its associated socioeconomic factors from January 2000 to June 2020. Two reviewers conducted the study selection, data extraction, and quality appraisal. The secular trend of the CHE rate was examined, and factors associated with CHE were explored using subgroup analysis and meta-regression.ResultsA total of 118 eligible studies with 1,771,726 participants were included. From 2000 to 2020, the overall CHE rate was 25.2% (95% CI: 23.4%−26.9%) in China. The CHE rate continued to rise from 13.0% in 2000 to 32.2% in 2020 in the general population. The CHE rate was higher in urban areas than in rural areas, higher in the western than the northeast, eastern, and central region, in the elderly than non-elderly, in low-income groups than non-low-income groups, in people with cancer, chronic infectious disease, and cardio-cerebrovascular diseases (CCVD) than those with non-chronic disease group, and in people with NCMS than those with URBMI and UEBMI. Multiple meta-regression analyses found that low-income, cancer, CCVD, unspecified medical insurance type, definition 1 and definition 2 were correlated with the CHE rate, while other factors were all non-significantly correlated.ConclusionIn the past two decades, the CHE rate in China has been rising. The continuous rise of health expenditures may be an important reason for the increasing CHE rate. Age, income level, and health status affect the CHE rate. Therefore, it is necessary to find ways to meet the medical needs of residents and, at the same time, control the unreasonable rapid increase in health expenditures in China.

Purpose: This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the smooth muscle cells (SMCs) heterogeneity and functions among various cell types.Methods: Male Apolipoprotein deficient (ApoE−/−) mice at 28 weeks of age were infused with Ang II (2,500 ng/kg/min) to induce AD. Aortas from euthanized mice were harvested after 7 days for 10×Genomics single-cell RNA sequencing (scRNA-seq), followed by the identification of cell types and differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted.Results: AD was successfully induced in ApoE−/− mice. scRNA-seq identified 15 cell clusters and nine cell types, including non-immune cells (endothelials, fibroblasts, and SMCs) and immune cells (B cells, natural killer T cell, macrophages, dendritic cells, neutrophils, and mast cells). The relative numbers of SMCs were remarkably changed, and seven core DEGs (ACTA2,IL6,CTGF,BGN,ITGA8,THBS1, and CDH5) were identified in SMCs. Moreover, we found SMCs can differentiate into 8 different subtypes through single-cell trajectory analysis.Conclusion: scRNA-seq technology can successfully identify unique cell composition in experimental AD. To our knowledge, this is the first study that provided the complete cellular landscape in AD tissues from mice, seven core DEGs and eight subtypes of SMCs were identified, and the SMCs have evolution from matrix type to inflammatory type.

Doxorubicin (DOX) is an anthracycline antibiotic that is used extensively for the management of carcinoma; however, its clinical application is limited due to its serious cardiotoxic side effects. Ferroptosis represents iron-dependent and reactive oxygen species (ROS)-related cell death and has been proven to contribute to the progression of DOX-induced cardiomyopathy. Fisetin is a natural flavonoid that is abundantly present in fruits and vegetables. It has been reported to exert cardioprotective effects against DOX-induced cardiotoxicity in experimental rats. However, the underlying mechanisms remain unknown. The present study investigated the cardioprotective role of fisetin and the underlying molecular mechanism through experiments in the DOX-induced cardiomyopathy rat and H9c2 cell models. The results revealed that fisetin treatment could markedly abate DOX-induced cardiotoxicity by alleviating cardiac dysfunction, ameliorating myocardial fibrosis, mitigating cardiac hypertrophy in rats, and attenuating ferroptosis of cardiomyocytes by reversing the decline in the GPX4 level. Mechanistically, fisetin exerted its antioxidant effect by reducing the MDA and lipid ROS levels and increasing the glutathione (GSH) level. Moreover, fisetin exerted its protective effect by increasing the SIRT1 expression and the Nrf2 mRNA and protein levels and its nuclear translocation, which resulted in the activation of its downstream genes such as HO-1 and FTH1. Selective inhibition of SIRT1 attenuated the protective effects of fisetin in the H9c2 cells, which in turn decreased the GSH and GPX4 levels, as well as Nrf2, HO-1, and FTH1 expressions. In conclusion, fisetin exerts its therapeutic effects against DOX-induced cardiomyopathy by inhibiting ferroptosis via SIRT1/Nrf2 signaling pathway activation.

In this contribution, we studied the effect of fluorine substitution on photogenerated charge generation, transport, and recombination in polymer solar cells. Two conjugated polymer materials, PBDTTT-E (fluorine free) and PTB7 (one fluorine substitution), were compared thoroughly. Meanwhile, various characterization techniques, including atomic force microscopy, steady-state spectroscopy, transient absorption spectroscopy, spectroelectrochemistry, and electrical measurements, were employed to analyse the correlation between molecular structure and device performance. The results showed that the influence of fluorine substitution on both the exciton binding energy of the polymer and the carrier recombination dynamics in the ultrafast timescale on the polymer was weak. However, we found that the fluorine substitution could enhance the exciton lifetime in neat polymer film, and it also could increase the mobility of photogenerated charge. Moreover, it was found that the SOMO energy level distribution of the donor in a PTB7:PC71BM solar cell could facilitate hole transport from the donor/acceptor interface to the inner of the donor phase, showing a better advantage than the PBDTTT-E:PC71BM solar cell. Therefore, fluorine substitution played a critical role for high-efficiency polymer solar cells.

Background and Purpose: It is well known that there is a wide range of different pathological stages related to Alzheimer's disease (AD) among patients with amnestic mild cognitive impairment (aMCI). Further refinement of the stages based on neuropsychological and neuroimaging methods is important for earlier disease detection, as well as for the development and evaluation of disease-modifying interventions. Materials and Methods: In this cross-sectional study, 125 aMCI patients were classified into declined progressively three stages of mild, moderate and severe, utilizing the extreme groups approach (EGA) based on their memory function. Fifty-two patients, in addition to 24 cognitively normal subjects, were included in further structural MRI analyses. Characteristics of cognitive functions and brain structures across these newly defined stages were explored through general linear models. Results: Almost all the non-memory cognitive functions showed progressive decline as memory function deteriorated. In addition, medial structures including the right hippocampus, right lingual and left fusiform gyrus, presented with greater gray matter (GM) atrophy during the later stages of aMCI (corrected p < 0.05). Correlations were found between GM volume of the lingual gyrus and processing speed (r = 0.419, p = 0.003) and between the fusiform gyrus and general cognitive function (r = 0.281, p = 0.046). Moreover, both cognitive function and GM volume presented non-linear trajectories over stages of aMCI. Conclusion: Our study characterized the cognitive profiles along with the degree of episodic memory impairment, and these three stages of aMCI showed non-linear progressive decline in cognitive functions and GM volumes. [ABSTRACT FROM AUTHOR]

The electrical conductivities of hydrous olivine (Ol) aggregates and Ol–H2O, Ol–NaCl–H2O (salinity: 1–21 wt%; fluid fraction: 5.1–20.7 vol%), Ol–KCl–H2O (salinity: 5 wt%; fluid fraction: 10.9–14.0 vol%) and Ol–CaCl2–H2O systems (salinity: 5 wt%; fluid fraction: 10.7–13.7 vol%) were measured at 2.0–3.0 GPa and 773–1073 K using a multi-anvil apparatus. The electrical conductivity of saline fluid-bearing olivine aggregates slightly increases with increasing pressure and temperature, and the electrical conductivities of both hydrous and saline fluid-bearing samples are well described by an Arrhenius relation. The dihedral angle of the saline fluids is approximately 50° in the Ol–NaCl–H2O system with 5 wt% NaCl and 5.1 vol% fluids, which implies that the fluids were interconnected along grain boundaries under the test conditions. The electrical conductivities of the Ol–NaCl–H2O system with 5 wt% NaCl and 5.1 vol% fluids are ∼two to four orders of magnitude higher than those of hydrous olivine aggregates. The salinity and fluid fraction moderately enhance the sample electrical conductivities owing to the interconnectivity of the saline fluids. The activation enthalpies of the electrical conductivities for the Ol–NaCl–H2O systems range from 0.07 to 0.36 eV, and Na+, Cl−, H+, OH−, and soluble ions from olivine are proposed to be the main charge carriers. For a fixed salinity and fluid fraction, the electrical conductivities of the Ol–NaCl–H2O system resemble the Ol–KCl–H2O system but are slightly higher than that of the Ol–CaCl2–H2O system. The Ol–NaCl–H2O system with a salinity of ∼5 wt% NaCl and fluid fraction larger than 1.8 vol% can be employed to reasonably explain the origin of the high-conductivity anomalies observed in mantle wedges.

White matter lesions (WMLs) are notable for their high prevalence and have been demonstrated to be a potential neuroimaging biomarker of early diagnosis of Alzheimer's disease. This study aimed to identify the brain functional and structural mechanisms underlying cognitive decline observed in mild WMLs. Multi-domain cognitive tests, as well as resting-state, diffusion tensor and structural images were obtained on 42 mild WMLs and 42 age/sex-matched healthy controls. For each participant, we examined the functional connectivity (FC) of three resting-state networks (RSNs) related to the changed cognitive domains: the default mode network (DMN) and the bilateral fronto-parietal network (FPN). We also performed voxel-based morphometry analysis to compare whole-brain gray matter (GM) volume, atlas-based quantification of the white matter tracts interconnecting the RSNs, and the relationship between FC and structural connectivity. We observed FC alterations in the DMN and the right FPN combined with related white matter integrity disruption in mild WMLs. However, no significant GM atrophy difference was found. Furthermore, the right precuneus FC in the DMN exhibited a significantly negative correlation with the memory test scores. Our study suggests that in mild WMLs, dysfunction of RSNs might be a consequence of decreased white matter structural connectivity, which further affects cognitive performance. [ABSTRACT FROM AUTHOR]

Background: One of the important pathogenesis of acute respiratory distress syndrome (ARDS) is the dysfunction of pulmonary microvascular endothelial barrier induced by a hyperinflammatory immune response. However, the potential mechanisms of such an imbalance in pulmonary microvascular endothelial cells (PMVECs) are not yet understood.Purpose: Explore the molecular mechanism of endothelial barrier dysfunction induced by inflammatory immune cytokines in ARDS, and find a therapeutic target for this syndrome.Methods: Rat PMVECs were cultured to form a monolayer. Immunofluorescence, flow cytometry, and Western blotting were selected to detect the distribution and the expression level of phosphorylated Ezrin protein and Ezrin protein. Transendothelial electrical resistance (TER) and transendothelial fluxes of fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (BSA) were utilized to measure the permeability of the cell monolayer. Ezrin short hairpin RNA (shRNA) and Ezrin 567-site threonine mutant (EzrinT567A) were used to examine the role of Ezrin protein and phosphorylated Ezrin protein in endothelial response induced by tumor necrosis factor-alpha (TNF-α), respectively. The function of focal adhesion kinase (FAK) and Ras homolog gene family, member A (RhoA) signaling pathways were estimated by inhibitors and RhoA/FAK shRNA in TNF-α-stimulated rat PMVECs. The activation of FAK and RhoA was assessed by Western blotting or pull-down assay plus Western blotting.Results: The TER was decreased after TNF-α treatment, while the Ezrin protein phosphorylation was increased in a time- and dose-dependent manner. The phosphorylated Ezrin protein was localized primarily at the cell periphery, resulting in filamentous actin (F-actin) rearrangement, followed by a significant decrease in TER and increase in fluxes of FITC-BSA. Moreover, FAK and RhoA signaling pathways were required in the phosphorylation of Ezrin protein, and the former positively regulated the latter.Conclusion: The phosphorylated Ezrin protein was induced by TNF-α via the FAK/RhoA signaling pathway leading to endothelial hyperpermeability in PMVECs.

Background: In patients with chronic obstructive pulmonary disease (COPD), acute exacerbations affect patients' health and can lead to death. This study was aimed to develop a prediction model for in-hospital mortality in patients with acute exacerbations of COPD (AECOPD).Method: A retrospective study was performed in patients hospitalized for AECOPD between 2015 and 2019. Patients admitted between 2015 and 2017 were included to develop model and individuals admitted in the following 2 years were included for external validation. We analyzed variables that were readily available in clinical practice. Given that death was a rare outcome in this study, we fitted Firth penalized logistic regression. C statistic and calibration plot quantified the model performance. Optimism-corrected C statistic and slope were estimated by bootstrapping. Accordingly, the prediction model was adjusted and then transformed into risk score.Result: Between 2015 and 2017, 1,096 eligible patients were analyzed, with a mean age of 73 years and 67.8% male. The in-hospital mortality was 2.6%. Compared to survivors, non-survivors were older, more admitted from emergency, more frequently concomitant with respiratory failure, pneumothorax, hypoxic-hypercarbic encephalopathy, and had longer length of stay (LOS). Four variables were included into the final model: age, respiratory failure, pneumothorax, and LOS. In internal validation, C statistic was 0.9147, and the calibration slope was 1.0254. Their optimism-corrected values were 0.90887 and 0.9282, respectively, indicating satisfactory discrimination and calibration. When externally validated in 700 AECOPD patients during 2018 and 2019, the model demonstrated good discrimination with a C statistic of 0.8176. Calibration plot illustrated a varying discordance between predicted and observed mortality. It demonstrated good calibration in low-risk patients with predicted mortality rate ≤10% (P = 0.3253) but overestimated mortality in patients with predicted rate >10% (P < 0.0001). The risk score of 20 was regarded as a threshold with an optimal Youden index of 0.7154.Conclusion: A simple prediction model for AECOPD in-hospital mortality has been developed and externally validated. Based on available data in clinical setting, the model could serve as an easily used instrument for clinical decision-making. Complications emerged as strong predictors, underscoring an important role of disease management in improving patients' prognoses during exacerbation episodes.

Metastatic cervical carcinoma from unknown primary (MCCUP) accounts for 1–4% of all head and neck tumors, and identifying the primary site in MCCUP is challenging. The most common histopathological type of MCCUP is squamous cell carcinoma (SCC), and it remains difficult to identify the primary site pathologically. Therefore, it seems necessary and urgent to develop novel and effective methods to determine the primary site in MCCUP. In the present study, the RNA sequencing data of four types of SCC and Pan-Cancer from the cancer genome atlas (TCGA) were obtained. And after data pre-processing, their differentially expressed genes (DEGs) were identified, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these significantly changed genes of four types of SCC share lots of similar molecular functions and histological features. Then three machine learning models, [Random Forest (RF), support vector machine (SVM), and neural network (NN)] which consisted of ten genes to distinguish these four types of SCC were developed. Among the three models with prediction tests, the RF model worked best in the external validation set, with an overall predictive accuracy of 88.2%, sensitivity of 88.71%, and specificity of 95.42%. The NN model is the second in efficacy, with an overall accuracy of 82.02%, sensitivity of 81.23%, and specificity of 93.04%. The SVM model is the last, with an overall accuracy of 76.69%, sensitivity of 74.81%, and specificity of 90.84%. The present analysis of similarities and differences among the four types of SCC, and novel models developments for distinguishing four types of SCC with informatics methods shed lights on precision MCCUP diagnosis in the future.

C4 photosynthesis is a complex trait that evolved from its ancestral C3 photosynthesis by recruiting pre-existing genes. These co-opted genes were changed in many aspects compared to their counterparts in C3 species. Most of the evolutionary changes of the C4 shuttle enzymes are well characterized, however, evolutionary changes for the recruited metabolite transporters are less studied. Here we analyzed the evolutionary changes of the shuttle enzyme phosphoenolpyruvate (PEP) transporter (PPT) during its recruitment from C3 to C4 photosynthesis. Our analysis showed that among the two PPT paralogs PPT1 and PPT2, PPT1 was the copy recruited for C4 photosynthesis in multiple C4 lineages. During C4 evolution, PPT1 gained increased transcript abundance, shifted its expression from predominantly in root to in leaf and from bundle sheath cell to mesophyll cell, and gained more rapid and long-lasting responsiveness to light. Modifications occurred in both regulatory and coding regions in C4 PPT1 as compared to C3 PPT1, however, the PEP transporting function of PPT1 remained. We found that PPT1 of a Flaveria C4 species recruited a MEM1 B submodule in the promoter region, which might be related to the increased transcript abundance of PPT1 in C4 mesophyll cells. The case study of PPT further suggested that high transcript abundance in a proper location is of high priority for PPT to support C4 function.

BackgroundDepression is a leading cause of disability worldwide and is a major contributor to the overall global burden of disease, but its etiology is poorly understood. It has been reported that a disrupted biological rhythm, in terms of a shortened light duration and total darkness, can cause depression-like behaviors in animals. Blue light was reported to have an inhibitory effect on melatonin, which is considered an important clock rhythm biomarker. In the present study, we investigated the effects of blue light deprivation on depressive-like behaviors in gerbils and explored the underlying mechanisms.MethodsGerbils were housed under white light with a filter to block the blue light or without a filter. The behaviors of the gerbils were observed. The biological rhythm, 5-HT, hypothalamic-pituitary-adrenal (HPA) axis and melanopsin pathway were analyzed.ResultsWe found that blue light deprivation (BLD) induced depression-like behavior in gerbils. Melatonin lost its rhythm, and corticosterone (CORT) levels decreased in the morning in the BLD group. Lower corticotropin-releasing hormone (CRH) in the hypothalamus and lower adrenocorticotropin hormone (ACTH)/CORT in serum were observed after BLD. Furthermore, 5-HT in the serum and brain were decreased after BLD. Additionally, BLD affected the blue light sensitivity protein melanopsin and its pathway, with downregulation of the proteins melanopsin, PKCα, and c-Fos and the mRNA levels of c-fos and trpc3 and upregulation of the protein p-PKCα.ConclusionsOur findings indicated that BLD might produce depression-like behaviors in gerbils. Melatonin arrhythmicity, HPA axis abnormalities, 5-HT decreases and melanopsin pathway changes might be associated with the depression behavioral phenotype in gerbils.