Temperature and nutrients drive distinct successions between diatoms and dinoflagellates over the past 40 years: Implications for climate warming and eutrophication.

Diatoms and dinoflagellates are two typical functional groups of phytoplankton, playing important roles in ecosystem processes and biogeochemical cycles. Changes in diatoms and dinoflagellates are thought to be one of the possible mechanisms for the increase in harmful algal blooms (HABs), due to changing hydrological conditions associated with climate change and human activities. However, little is known about their ability to adapt to changing ocean environments, thus making it difficult to know whether and how they are adapting. By analyzing a 44-year monitoring dataset in the central Bohai Sea during 1978-2021, we found that the abundance ratio of diatoms to dinoflagellates showed a decreasing trend seasonally and ecologically, indicating that the phytoplankton community underwent distinct successional processes from diatom dominance to diatom-dinoflagellate co-dominance. These processes exhibited varying responses to temperature, nutrient concentrations and ratios, and their interactions, of which temperature primarily drove the seasonal succession whereas nutrients were responsible for the ecological succession. Specifically, diatoms showed a preference for lower temperatures and higher DIP concentrations, and were able to tolerate lower DIN at lower temperatures. In contrast, dinoflagellates tended to prevail at conditions of warming and high N/P ratios. These different traits of diatoms and dinoflagellates reflected the fact that warming as a result of rising temperature and eutrophication as a consequence of nutrient input would favor dinoflagellates over diatoms. Moreover, the increasing dominance of dinoflagellates indicated that dinoflagellate blooms were likely to become more frequent and intense in the central Bohai Sea.

Environmental controls on the seasonal variations of diatoms and dinoflagellates in the Qingdao coastal region, the Yellow Sea.

Diatoms and dinoflagellates are two typical functional groups of phytoplankton assemblages, which play a crucial role in the structure and functioning of most marine ecosystems. To date, a novel challenge in ecology and biogeochemistry is to address the influences of environmental changes associated with climate change and human activities on the dynamics of diatoms and dinoflagellates. However, the knowledge of the key environmental factors controlling the diatom-dinoflagellate dynamics remains to be improved, particularly in the coastal ecosystems. Therefore, we conducted four cruises along the Qingdao coastline in spring, summer, autumn, and winter 2022 to explore how diatoms and dinoflagellates varied in response to regional environmental changes. The results showed that the phytoplankton communities were dominated by diatoms and dinoflagellates in terms of abundance and species diversity throughout the year in the study region. Yet, there were significant seasonal variability of diatoms and dinoflagellates across the four seasons. For example, diatom species was the most diverse during autumn, and the higher average abundance was observed in the fall and winter. In contrast, the average abundance of dinoflagellates was maximum during the summer and minimum in the autumn season. Moreover, the abundance and species ratios of diatoms/dinoflagellates (dia/dino) also showed significant seasonal variations in the region. The dia/dino abundance ratio was lowest in summer, while the dia/dino species ratio showed an increasing trend from spring to fall and a slight descending trend during winter. Based on the redundancy analysis, we revealed that diatoms and dinoflagellates responded differently to various environmental variables in different seasons, of which temperature and nutrients (especially dissolved inorganic nitrogen, DIN) had highly significant correlations with both the dia/dino abundance and species ratios. Thus, we suggested that temperature and DIN were the key factors controlling the seasonal dynamics of diatoms and dinoflagellates in the Qingdao coastal area.

Unveiling the neuroprotection effects of Volvalerenic acid A: Mitochondrial fusion induction via IDO1-mediated Stat3-Opa1 signaling pathway.

BACKGROUND: Ischemic stroke is a leading cause of death and long-term disability worldwide. Studies have suggested that cerebral ischemia induces massive mitochondrial damage. Valerianic acid A (VaA) is the main active ingredient of valerianic acid with neuroprotective activity. PURPOSE: This study aimed to investigate the neuroprotective effects of VaA with ischemic stroke and explore the underlying mechanisms. METHOD: In this study, we established the oxygen-glucose deprivation and reperfusion (OGD/R) cell model and the middle cerebral artery occlusion and reperfusion (MCAO/R) animal model in vitro and in vivo. Neurological behavior score, 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining and Hematoxylin and Eosin (HE) Staining were used to detect the neuroprotection of VaA in MCAO/R rats. Also, the levels of ROS, mitochondrial membrane potential (MMP), and activities of NAD+ were detected to reflect mitochondrial function. Mechanistically, gene knockout experiments, transfection experiments, immunofluorescence, DARTS, and molecular dynamics simulation experiments showed that VaA bound to IDO1 regulated the kynurenine pathway of tryptophan metabolism and prevented Stat3 dephosphorylation, promoting Stat3 activation and subsequent transcription of the mitochondrial fusion-related gene Opa1. RESULTS: We showed that VaA decreased the infarct volume in a dose-dependent manner and exerted neuroprotective effects against reperfusion injury. Furthermore, VaA promoted Opa1-related mitochondrial fusion and reversed neuronal mitochondrial damage and loss after reperfusion injury. In SH-SY5Y cells, VaA (5, 10, 20 µM) exerted similar protective effects against OGD/R-induced injury. We then examined the expression of significant enzymes regulating the kynurenine (Kyn) pathway of the ipsilateral brain tissue of the ischemic stroke rat model, and these enzymes may play essential roles in ischemic stroke. Furthermore, we found that VaA can bind to the initial rate-limiting enzyme IDO1 in the Kyn pathway and prevent Stat3 phosphorylation, promoting Stat3 activation and subsequent transcription of the mitochondrial fusion-related gene Opa1. Using in vivo IDO1 knockdown and in vitro IDO1 overexpressing models, we demonstrated that the promoted mitochondrial fusion and neuroprotective effects of VaA were IDO1-dependent. CONCLUSION: VaA administration improved neurological function by promoting mitochondrial fusion through the IDO1-mediated Stat3-Opa1 pathway, indicating its potential as a therapeutic drug for ischemic stroke.

Microbial community structure in a constructed wetland based on a recirculating aquaculture system: Exploring spatio-temporal variations and assembly mechanisms.

The diversity, composition and performance of microbial communities within constructed wetlands (CW) were markedly influenced by spatio-temporal variations. A pilot-scale integrated vertical-flow constructed wetland (IVCW) as the biological purification unit within a recirculating aquaculture system (RAS) was established and monitored in this study. The investigation aimed to elucidate the responses of community structure, co-occurrence networks, and assembly mechanisms of the microbial community to spatial and temporal changes. Spatially, all a-diversity indices and microbial networks complexity were significantly higher in the upstream pool of the IVCW than in the downstream pool. Temporally, the richness increased over time, while the evenness showed a decreasing trend. The number of nodes and edges of microbial networks increased over time. Notably, the stable pollutant removal efficiencies were observed during IVCW operations, despite a-diversity and bacterial community networks exhibited significant variations across time. Functional redundancy emerged as a likely mechanism contributing to the stability of microbial ecosystem functions. Null model and neutral model analyses revealed the dominance of deterministic processes shaping microbial communities over time, with deterministic influences being more pronounced at lower a-diversity levels. DO and inorganic nitrogen emerged as the principal environmental factor influencing microbial community dynamics. This study provides a theoretical foundation for the regulation of microbial communities and environmental factors within the context of IVCW.

The facilitating effects of KRT80 on chemoresistance, lipogenesis, and invasion of esophageal cancer.

Keratin 80 (KRT80) is a filament protein that makes up one of the major structural fibers of epithelial cells, and involved in cell differentiation and epithelial barrier integrity. Here, KRT80 mRNA expression was found to be higher in esophageal cancer than normal epithelium by RT-PCR and bioinformatics analysis (p < .05), opposite to KRT80 methylation (p < .05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in esophageal cancer (p < .05). KRT80 mRNA expression was positively correlated with the differentiation, infiltration of immune cells, and poor prognosis of esophageal cancer (p < .05). KRT80 mRNA expression was positively linked to no infiltration of immune cells, the short survival time of esophageal cancers (p < .05). The differential genes of KRT80 mRNA were involved in fat digestion and metabolism, peptidase inhibitor, and intermediate filament, desosome, keratinocyte differentiation, epidermis development, keratinization, ECM regulator, complement cascade, metabolism of vitamins and co-factor (p < .05). KRT-80-related genes were classified into endocytosis, cell adhesion molecule binding, cadherin binding, cell-cell junction, cell leading edge, epidermal cell differentiation and development, T cell differentiation and receptor complex, plasma membrane receptor complex, external side of plasma membrane, metabolism of amino acids and catabolism of small molecules, and so forth (p < .05). KRT80 knockdown suppressed anti-apoptosis, anti-pyroptosis, migration, invasion, chemoresistance, and lipogenesis in esophageal cancer cells (p < .05), while ACC1 and ACLY overexpression reversed the inhibitory effects of KRT80 on lipogenesis and chemoresistance. These findings indicated that up-regulated expression of KRT80 might be involved in esophageal carcinogenesis and subsequent progression, aggravate aggressive phenotypes, and induced chemoresistance by lipid droplet assembly and ACC1- and ACLY-mediated lipogenesis.

Unprecedented phytoplankton blooms in autumn/winter in the southern Bohai Sea (China) due to high Yellow River discharge: Implications of extreme rainfall events.

The occurrence of abnormal phytoplankton blooms is one of the significant changes in coastal ecosystems due to climate change. However, the underlying mechanism of such blooms remains poorly understood due to the complexity of the system. In this study, the data from numerous observations was used to elucidate the unprecedented phytoplankton blooms in the autumn and winter of 2021 in Laizhou Bay, a typical aquaculture bay in the southern Bohai Sea of China. The abundance of phytoplankton cells increased by more than tenfold in the southern waters compared to that in the same period from 2019 to 2020. The phytoplankton bloom was first observed in winter in the Bohai Sea, with the cell abundance in the southern bay exceeding 108 cells L-1 in December 2021. The diversity and evenness of phytoplankton communities decreased in the southern area. Cerataulina pelagica was the dominant algae, comprising 69 % of the total phytoplankton in October and 99 % in December. In autumn 2021, the largest flood of the Yellow River in recent decades occurred. This was attributed to extreme rainfall events within the river basin. The input of substantial riverine nutrients played a significant role in promoting phytoplankton blooms. Correlation analysis indicated the important cumulative impact of the Yellow River on phytoplankton blooms rather than a direct short-term effect. Numerical modeling results indicated that exceptionally high Yellow River discharge in autumn could significantly affect the entire bay from autumn to the following spring. This study may contribute to understanding the abnormal phytoplankton blooms in coastal waters and provide valuable insights for environmental management in river basins and coastal waters.

The characteristics of trimethylamine N-oxide content in different classes of marine animals over the coastal and offshore areas of China.

Trimethylamine N-oxide (TMAO) is widely present in marine animals. However, the characteristics of TMAO content in different classes of marine animals are insufficiently understood. In this study, the TMAO content in 79 marine animals (48 species, 7 classes) collected in the coastal and offshore areas of China during year 2019-2022 was analysed. The results showed that the TMAO content of the total samples varied from 0 to 139.19 mmol kg-1. The TMAO content in the classes Bivalvia, Gastropoda, Polychaeta and Holothuroidea varied from 0.06 ± 0.09 to 0.38 ± 0.63 mmol kg-1, but it varied from 30.20 ± 24.20 to 75.90 ± 38.59 mmol kg-1 in the classes Crustacea, Cephalopoda, and Osteichthyes. The TMAO content in the latter 3 classes was 2-3 orders of magnitude higher than that of the former 4 classes. It was inferred that the significant difference was related to the food sources or physiological metabolic mechanisms of different classes.

Environmental forcing of phytoplankton carbon-to-diversity ratio and carbon-to-chlorophyll ratio: A case study in Jiaozhou Bay, the Yellow Sea.

The relationships between phytoplankton carbon (C) biomass and diversity (i.e., C-to-H' ratio) and chlorophyll a (i.e., C-to-Chl a ratio) are good indicators of marine ecosystem functioning and stability. Here we conducted four cruises spanning 2 years in Jiaozhou Bay to explore the dynamics of C-to-H' and C-to-Chl a ratios. The results showed that the phytoplankton C biomass and diversity were dominated by diatoms, followed by dinoflagellates. The average C-to-H' ratio ranged from 84.10 to 912.17, with high values occurring in the northern region of the bay. In contrast, the average C-to-Chl a ratio ranged between 15.55 and 89.47, and high values primarily appeared in the northern or northeastern part of the bay. In addition, the redundancy analysis showed that temperature and phosphate (DIP) were significantly correlated with both ratios in most cases, indicating that temperature and DIP may be key factors affecting the dynamics of C-to-H' and C-to-Chl a ratios.

Effect of the molecular weight of DOM on the indirect photodegradation of fluoroquinolone antibiotics.

Dissolved organic matter (DOM) is ubiquitous and widespread in natural water and influences the transformation and removal of antibiotics. Nevertheless, the influence of DOM molecular weight (MW) on the indirect photodegradation of antibiotics has rarely been reported. This study attempted to explore the influence of the molecular weight of DOM on the indirect photodegradation of two fluoroquinolone antibiotics (FQs), ofloxacin (OFL) and norfloxacin (NOR), by using UV-vis absorption and fluorescence spectroscopy. The results showed that indirect photodegradation was considered the main photodegradation pathway of FQs in DOM fractions. Triplet-state excited organic matter (3DOM*) and singlet oxygen (1O2) were the main reactive intermediates (RIs) that affected the indirect photodegradation of FQs. The indirect photodegradation rate of FQs was significantly promoted in DOM fractions, especially in the low molecular weight DOM fractions (L-MW DOM, MW < 10 kDa). The results of excitation-emission matrix spectroscopy combined with parallel factor analysis (EEM-PARAFAC) showed that terrestrial humic-like substances had a higher humification degree and fluorophore content in L- MW DOM fractions, which could produce more 3DOM* and 1O2 to promote the indirect photodegradation of FQs. This study provided new insight into the effects of DOM at the molecular weight level on the indirect photodegradation of antibiotics in natural water.

Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly.

BACKGROUND: Regenerating gene 4 (REG4) has been proved to be carcinogenic in some cancers, but its manifestation and possible carcinogenic mechanisms in colorectal cancer (CRC) have not yet been elucidated. Our previous study found that the drug resistance of CRC cells may be closely linked to their fat metabolism. AIM: To explore the role of REG4 in CRC and its association with lipid droplet formation and chemoresistance. METHODS: We conducted a meta-analysis and bioinformatics and pathological analyses of REG4 expression in CRC. The effects of REG4 on the phenotypes and related protein expression were also investigated in CRC cells. We detected the impacts of REG4 on the chemoresistance and lipid droplet formation in CRC cells. Finally, we analyzed how REG4 regulated the transcription and proteasomal degradation of lipogenic enzymes in CRC cells. RESULTS: Compared to normal mucosa, REG4 mRNA expression was high in CRC (P < 0.05) but protein expression was low. An inverse correlation existed between lymph node and distant metastases, tumor-node-metastasis staging or short overall survival and REG4 mRNA overexpression (P < 0.05), but vice versa for REG4 protein expression. REG4-related genes included: Chemokine activity; taste receptors; protein-DNA and DNA packing complexes; nucleosomes and chromatin; generation of second messenger molecules; programmed cell death signals; epigenetic regulation and DNA methylation; transcription repression and activation by DNA binding; insulin signaling pathway; sugar metabolism and transfer; and neurotransmitter receptors (P < 0.05). REG4 exposure or overexpression promoted proliferation, antiapoptosis, migration, and invasion of DLD-1 cells in an autocrine or paracrine manner by activating the epidermal growth factor receptor-phosphoinositide 3-kinase-Akt-nuclear factor-κB pathway. REG4 was involved in chemoresistance not through de novo lipogenesis, but lipid droplet assembly. REG4 inhibited the transcription of acetyl-CoA carboxylase 1 (ACC1) and ATP-citrate lyase (ACLY) by disassociating the complex formation of anti-acetyl (AC)-acetyl-histone 3-AC-histone 4-inhibitor of growth protein-5-si histone deacetylase;-sterol-regulatory element binding protein 1 in their promoters and induced proteasomal degradation of ACC1 or ACLY. CONCLUSION: REG4 may be involved in chemoresistance through lipid droplet assembly. REG4 reduces expression of de novo lipid synthesis key enzymes by inhibiting transcription and promoting ubiquitination-mediated proteasomal degradation.

Contrasting effects of river inflow and seawater intrusion on zooplankton community structure in Jiaozhou bay, the Yellow Sea.

Environmental changes associated with river inflow and seawater intrusion are known to affect zooplankton communities in coastal systems, but how zooplankton respond to these environmental changes remains unclear at present. Here we explored the effects of river inflow and seawater intrusion on zooplankton community structure in Jiaozhou Bay. The results showed that the river inflow and seawater intrusion are key in driving zooplankton dynamics, but with contrasting effects. According to the distinct hydrographic conditions, the sampling area could be geographically divided into the river inflow area with low-salinity and high-nutrient conditions (i.e., EIZ) and the seawater intrusion zone with high-salinity and low-nutrient conditions (i.e., SIZ). There were significant differences in zooplankton communities (e.g., abundance and species composition) between the two regions with seasonal changes. For example, the zooplankton abundance was significantly higher in the SIZ than in the EIZ during spring, whereas an opposite pattern was observed for the summer season. In contrast, the species richness was higher in the EIZ than in the SIZ in spring, while an opposite variation trend was observed during summer. These results together suggested that the river inflow and seawater intrusion had contrasting effects on zooplankton community structure in different seasons. According to the canonical correspondence analysis, we observed that the zooplankton community structure was mainly driven by temperature, chlorophyll a (Chl a), and nutrients in the EIZ, but it was largely affected by salinity in the SIZ. The implication is that changes in temperature, Chl a, and nutrients as a result of river inflow and changes in salinity as a consequence of seawater intrusion are key in driving the dynamics of zooplankton communities in Jiaozhou Bay.

Physiological response mechanism of heavy metal-resistant endophytic fungi isolated from the roots of Polygonatum kingianum.

This study aims to evaluate the tolerance of endophytic fungi isolated from the fibrous roots of Polygonatum kingianum to arsenic (As) and cadmium (Cd) and their physiological response mechanisms. Five isolated strains were obtained with EC50 values for As(V) ranging from 421 to 1281 mg/L, while the other three strains tolerated Cd(II) with an EC50 range of 407-1112 mg/L. Morphological and molecular identification indicated that these eight strains were Cladosporium spp. belonging to dark septate endophytes (DSEs). The contents of metal ions in mycelium sharply increased, reaching 38.87 mg/kg for strain MZ-11 under As(V) stress and 0.33 mg/kg for fungus PR-2 under Cd(II). The physiological response revealed that the biomass decreased with increasing concentrations of As(V) or Cd(II), and the activity of superoxide dismutase significantly improved under the corresponding EC50 -concentration As/Cd of the strains, as well as the contents of antioxidant substances, including metallothionein, glutathione, malondialdehyde, melanin, and proline. Taken together, the filamentous fungi of Cladosporium spp. accounted for a high proportion of fungi isolated from the fibrous roots of P. kingianum and had a strong capacity to tolerate As(V) or Cd(II) stress by improving antioxidase activities and the content of antioxidant substances, and immobilization of metal ions in hyphae.

Spatial distribution and potential ecological risk assessment of heavy metals in the sediments of fishing ports along the coasts of the Yellow Sea and Bohai Sea.

More than 1,154 fishing ports are widely distributed in China's coastal areas. To date, however, few studies on the pollution and ecological risks of heavy metals in these fishing ports have been reported. In this study, the heavy metals of 148 sediment samples collected from 37 fishing ports along the coasts of the Yellow Sea and Bohai Sea were detected. The results showed that the average contents of Cu, Pb, Zn, and Cd were 53.58 ± 44.53, 27.90 ± 18.10, 143.52 ± 74.72 and 0.28 ± 0.15 mg/kg, respectively. Based on the geoaccumulation index (Igeo) and the potential ecological risk index (RI), we found that fishing ports were the most severely polluted by Cu, but Cd had the highest ecological risk, and most of fishing ports were in moderate potential ecological risk. The positive correlation between heavy metals and total organic carbon indicated that heavy metals in fishing ports were mainly affected by anthropogenic activities.

The promoting effects of GPR176 expression on proliferation, chemoresistance, lipogenesis and invasion of oesophageal cancer.

PURPOSE: As a member of the G-protein-coupled receptor 1 family, the G-protein-coupled receptor 176 (GPR176) gene encodes a glycosylated protein made up of 515 amino acids. The current study was performed to evaluate the impact of GPR176 on the clinicopathology and prognosis of oesophageal cancer, as well as uncover its molecular mechanisms. METHODS: Bioinformatics and clinical tissue samples were used to detect the expression and clinicopathological significance of GPR176 in oesophageal cancer. The expression, proliferation, migration and invasion, apoptosis and lipid droplet formation of GPR176 gene in oesophageal cancer were performed as phenotypic readouts. RESULTS: Here, RT-PCR and bioinformatic analyses revealed that GPR176 mRNA expression was significantly higher in oesophageal cancer than in normal mucosa (p < 0.05). GPR176 mRNA expression was associated with low weight and BMI, low T stage, low N and clinicopathological stage, low histological grade and favourable clinical outcome of oesophageal cancer (p < 0.05). The differential genes of GPR176 mRNA were involved in protein digestion and absorption, extracellular matrix constituent, endoplasmic reticulum lumen, among others (p < 0.05). GPR176-related genes were classified as being involved in oxidoreductase activity, actin and myosin complexes, lipid localisation and transport, among others (p < 0.05). GPR176 knockdown suppressed proliferation, anti-apoptotic and anti-pyroptotic properties, migration, invasion, chemoresistance and lipid droplet formation in oesophageal cancer cells (p < 0.05), while ACC1 and ACLY overexpression reversed the inhibitory effects of GPR176 silencing on lipid droplet formation and chemoresistance. CONCLUSION: These findings indicated that upregulated expression of GPR176 might be involved in oesophageal carcinogenesis and subsequent progression, aggressiveness, and induced chemoresistance by ACC1- and ACLY-mediated lipogenesis and lipid droplet assembly.

FAM64A aggravates proliferation, invasion, lipid droplet formation, and chemoresistance in gastric cancer: A biomarker for aggressiveness and a gene therapy target.

FAM64A is a mitogen-induced regulator of the metaphase and anaphase transition. Here, we found that FAM64A messenger RNA (mRNA) and protein expression levels were higher in gastric cancer tissue than in normal mucosa (p < .05). FAM64A methylation was negatively correlated with FAM64A mRNA expression (p < .05). The differentially expressed genes of FAM64A were mainly involved in digestion, potassium transporting or exchanging ATPase, contractile fibers, endopeptidase, and pancreatic secretion (p < .05). The FAM64A-related genes were principally categorized into ubiquitin-mediated proteolysis, cell cycle, chromosome segregation and mitosis, microtubule binding and organization, metabolism of amino acids, cytokine receptors, lipid droplet, central nervous system, and collagen trimer (p < .05). FAM64A protein expression was lower in normal gastric mucosa than intestinal metaplasia, adenoma, and primary cancer (p < .05), negatively correlated with older age, T stage, lymphatic and venous invasion, tumor, node, metastasis stage, and dedifferentiation (p < .05), and associated with a favorable overall survival of gastric cancer patients. FAM64A overexpression promoted proliferation, antiapoptosis, migration, invasion, and epithelial-mesenchymal transition via the EGFR/Akt/mTOR/NF-κB, while the opposite effect was observed for FAM64A knockdown. FAM64A also induced chemoresistance directly or indirectly through lipid droplet formation via ING5. These results suggested that upregulation of FAM64A expression might induce aggressive phenotypes, leading to gastric carcinogenesis and its subsequent progression. Thus, FAM64A could be regarded as a prognosis biomarker and a target for gene therapy.

Expression of SMARCA2 and SMARCA4 in gastric adenocarcinoma and construction of a nomogram prognostic model.

BACKGROUND: Aberrant expression of SWI/SNF complex subunits is closely associated with tumorigenesis. The clinicopathological and prognostic significance of altered SMARCA2 and SMARCA4 subunits has not been well evaluated in gastric adenocarcinoma. METHODS: We collected 1271 postoperative cases of gastric adenocarcinoma and then constructed tissue microarrays (TMA), from which we obtained the immunohistochemistry expression of SMARCA2 and SMARCA4. Next, we screened the variables related to the loss of SMARCA2 and SMARCA4 by univariate correlation analysis and multivariate logistic regression analysis. Then, we identified the variables related to prognosis by univariate and multivariate Cox regression analysis. Finally, we constructed a nomogram prognostic model and evaluated it. RESULTS: The loss of SMARCA2 and SMARCA4 occurred in 236 (18.57%) and 86 (6.77%) cases, respectively, including 26 cases of co-loss. After multivariate logistic regression, variables independently associated with SMARCA2 loss were T stage, differentiation status, WHO histological classification, and EBER. Variables independently associated with SMARCA4 loss were differentiation status, WHO histological classification, PD-L1, and MMR. Survival analysis revealed that the SMARCA2 and SMARCA4 lost groups showed worse survival than the corresponding present groups (P = 0.032 and P = 0.0048, respectively). Univariate and multivariate Cox analyses identified independent prognostic factors, including age, T stage, N stage, M stage, SMARCA2, and chemotherapy. CONCLUSION: The loss of SMARCA2 and SMARCA4 correlated with poor differentiation, leading to a worse prognosis. SMARCA2, as an independent prognostic factor, combined with other clinicopathological variables, established a novel nomogram prognostic model, which outperformed the AJCC TNM model.

Ginseng saponin metabolite 20(S)-protopanaxadiol relieves pulmonary fibrosis by multiple-targets signaling pathways.

Background: Panax ginseng Meyer is a representative Chinese herbal medicine with antioxidant and anti-inflammatory activity. 20(S)-Protopanaxadiol (PPD) has been isolated from ginseng and shown to have promising pharmacological activities. However, effects of PDD on pulmonary fibrosis (PF) have not been reported. We hypothesize that PDD may reverse inflammation-induced PF and be a novel therapeutic strategy. Methods: Adult male C57BL/6 mice were used to establish a model of PF induced by bleomycin (BLM). The pulmonary index was measured, and histological and immunohistochemical examinations were made. Cell cultures of mouse alveolar epithelial cells were analyzed with Western blotting, co-immunoprecipitation, immunofluorescence, immunohistochemistry, siRNA transfection, cellular thermal shift assay and qRT-PCR. Results: The survival rate of PPD-treated mice was higher than that of untreated BLM-challenged mice. Expression of fibrotic hallmarks, including α-SMA, TGF-ß1 and collagen I, was reduced by PPD treatment, indicating attenuation of PF. Mice exposed to BLM had higher STING levels in lung tissue, and this was reduced by phosphorylated AMPK after activation by PPD. The role of phosphorylated AMPK in suppressing STING was confirmed in TGF-ß1-incubated cells. Both in vivo and in vitro analyses indicated that PPD treatment attenuated BLM-induced PF by modulating the AMPK/STING signaling pathway. Conclusion: PPD ameliorated BLM-induced PF by multi-target regulation. The current study may help develop new therapeutic strategies for preventing PF.

High dimethylsulfoniopropionate concentrations in the surface seawater over the marginal seas of China and the Northwest Pacific Ocean during May-July of 2021 following La Niña.

The total dimethylsulfoniopropionate (DMSPt) concentrations over the surface seawater of China's marginal seas and the northwest Pacific Ocean (NWPO) in May-July 2021 (during the recessional period of La Niña) were analysed. The results showed that the DMSPt concentrations in the marginal seas of China varied from 4.73 to 775.96 nmol L-1, with an average value of 111.42 ± 129.30 nmol L-1 (average ± standard deviation). It was 2-12 times higher than those previously measured in the same seas and in the NWPO in this study. Significant positive correlations between DMSPt, chlorophyll-a and surface seawater temperature (SST) were observed in the SYS, the ECS and the NWPO. Moreover, their abnormally high SST was related to La Niña. These results suggested that high phytoplankton abundance was caused by abnormally high SST following La Niña, which further promoted DMSPt concentration increases. However, the increase of DMSPt was also related to other factors such as nutrients.

Identifying the key factors affecting the trimethylamine N-oxide content of teleost fishes collected from the marginal seas of China and the epipelagic zone of the northwest Pacific Ocean.

To identify the key factors influencing the trimethylamine N-oxide (TMAO) content of teleost fishes living in shallow seas and the epipelagic zone of the deep ocean, the muscle TMAO content was measured in 152 teleost fishes (21 species) collected from the marginal seas of China and the epipelagic zone of the northwest Pacific Ocean (NWPO) during May-July 2021. The results showed that the TMAO content in all fishes varied from 4.99 to 82.97 mmol kg-1, and it varied notably among different species, e.g., the highest average content (72.71 ± 8.22 mmol kg-1 in Argyrosomus argentatus) was 1 order of magnitude higher than the lowest one (Scomber japonicus), but the ratios of the highest content to the lowest content in each species varied from 1.29 to 3.28, suggesting that the interspecific variations in TMAO content were obviously greater than the intraspecific variations. Moreover, no correlation was observed between the TMAO content of the 152 fishes and the corresponding environmental factors of seawater depth, salinity and temperature, indicating that species played a more important role than environmental factors in driving TMAO accumulation. To exclude the influence of species, intraspecies correlations between TMAO content and environmental factors were analyzed. In the marginal seas of China, only ∼8 % of the TMAO content of teleost fishes (1 species) showed a positive correlation with salinity and depth, but ∼50 % of the TMAO content (5 species) was negatively correlated with temperature. Moreover, the TMAO content of the fish increased by 4.66 ± 1.38 % compared with their corresponding intraspecific average values for every 1 °C of temperature decrease. A similar phenomenon was also found in the TMAO content of pelagic teleost fishes in the NWPO, suggesting that temperature was a key environmental factor affecting the TMAO content of teleost fishes in shallow seas and the epipelagic zone of the deep ocean.

Picocyanobacteria-A non-negligible group for the export of biomineral silica to ocean depth.

Diatoms have long been thought to dominate the marine silicon (Si) cycle, as well as play an important role in the ocean's carbon (C) export, due to density-driven particle sedimentation. Research in the past decade has shed new light on the potential importance of picocyanobacteria to C export, although the sinking mechanism is still unclear. Interestingly, the recent discovery of Si accumulation by picocyanobacteria of the genus Synechococcus has strong implications for the marine Si cycle, which may also have profound influence on the oceanic C export. Understanding the mechanisms of Synechococcus Si accumulation and its ecological effects are therefore critical for addressing wider issues such as Si and C exports by small cells via biological pump. Here, we show that recent advances in process studies indicate that the presence of Si within picocyanobacteria may be a common and universal feature. Subsequently, we generalize four biochemical forms of Si potentially present in picocyanobacterial cells, which are all different from diatomaceous opal-A, and hypothesize that these various structures of Si phases may be several stage products of Si precipitation. At the same time, several aspects of Si dynamics in Synechococcus are also discussed emphatically. In addition, we provide a first estimate of picocyanobacteria Si stock and production for the global ocean, accounting for 12% of the global Si inventory and 45% of the global annual Si production in the surface ocean, respectively. The implication is that picocyanobacteria may exert a significant influence on the marine Si cycle, which is likely to alter our understanding of the long-term control of the oceanic Si cycling by diatoms. Finally, we summarize three possible mechanisms and pathways through which picocyanobacteria-derived Si can be transported to the deep ocean. Altogether, marine picocyanobacteria, despite very small in cell size, are a non-negligible group for the export of biomineral Si to deeper waters and ocean sediments.