Macrogenomics-Based Analysis of the Effects of Intercropped Soybean Photosynthetic Characteristics and Nitrogen-Assimilating Enzyme Activities on Yield at Different Nitrogen Levels.

Currently, China's soybean self-sufficiency rate is only 15%, highlighting the soybean crisis and the supply chain risks that pose a major threat to China's food security. Thus, it has become imperative to step up efforts to boost soybean production capacity while promoting the green and sustainable development of regional farmland ecosystems. In this context, the present study comprehensively investigated the effects of intercropping and nitrogen application rate on soybean yield, as well as the changes in gradients generated by different levels of nitrogen application. Based on six consecutive years of maize-soybean intercropping planting patterns, the inter-root soils of soybeans were collected at the flowering stage and evaluated for soil nitrogen content, nitrogen-assimilating enzyme activities, and microbial community composition of soybean, which were correlated with yield, to clarify the main pathways and modes of intercropping effects. The N2 level (80 kg·ha-1) was favourable for higher yield. In comparison to monocropping, the intercropping reduced yield by 9.65-13.01%, photosynthetic characteristics by 1.33-7.31%, and plant nitrogen-assimilating enzyme activities by 8.08-32.01% at the same level of N application. Likewise, soil urease and catalase activities were reduced by 9.22 and 1.80%, while soil nitrogen content declined by an average of 6.38%. Gemmatimonas and Bradyrhizobium enrichment significantly increased soil nitrogen content, photosynthetic characteristics, and soybean yield, while it was reduced by Candidatus_Udaeobacter and Candidatus_Solibacte enrichment. The results of this study provide a theoretical basis for further optimising maize-soybean intercropping, which is crucial for enhancing the agricultural production structure and improving the overall soybean production capacity.

Protective effects of baicalin against phenylarsine oxide-induced cytotoxicity in human skin keratinocytes.

Phenylarsine oxide (PAO) is a known environmental pollutant and skin keratinocytes are most seriously affected. Baicalin (BCN) was reported to have antioxidant and anti-inflammatory effects, but its protective effect against PAO toxicity is unknown. This study aimed at exploring whether baicalin can reverse the toxicity of human epidermal keratinocytes that are subjected to PAO exposure and underlying mechanisms. In silico analysis from a publicly accessible HaCaT cell transcriptome dataset exposed to chronic Arsenic showed significant differential expression of several genes, including the genes related to DNA replication. Later, we performed in vitro experiments, in which HaCaT cells were exposed to PAO (500 nM) in the existence of BCN (10-50 µM). Treatment of PAO alone induces the JNK, p38 and caspase-3 activation, which were engaged in the apoptosis induction, while the activity of AKT was significantly inhibited, which was engaged in the suppression of apoptosis. PAO suppressed SIRT3 expression and induced intracellular reactive oxygen species (ROS), causing a marked reduce in cell viability and apoptosis. However, BCN treatment restored the PAO-induced suppression of SIRT3 and AKT expression, reduced intracellular ROS generation, and markedly suppressed both caspase-3 activation and apoptosis induction. However, the protective effect of BCN was significantly attenuated after pretreatment with nicotinamide, an inhibitor of SIRT3. These findings indicate that BCN protects against cell death induced by PAO via inhibiting excessive intracellular ROS generation via restoring SIRT3 activity and reactivating downstream AKT pathway. In this study, we firstly shown that BCN is an efficient drug to prevent PAO-induced skin cytotoxicity, and these findings need to be confirmed by in vivo and clinical investigations.

Effect of hydraulic retention time on denitrification performance and microbial communities of solid-phase denitrifying reactors using polycaprolactone/corncob composite.

This study investigated the effect of hydraulic retention time (HRT) on the denitrification performance and microbial composition of reactors, packed with composite polycaprolactone and corncob carbon sources, during the treatment mariculture wastewater. The optimal HRT was 3 h, and average nitrogen removal efficiency was 99.00 %, 99.07 %, and 98.98 % in the HRT =3, 5, and 7 h groups, respectively. However, the 3 h group (DOC 2.91 mg/L) was the only group with a lower DOC concentration than that of the influent group (3.31 mg/L). Moreover, species richness was lower at HRT =3 h, with a greater proportion of denitrification-dominant phyla, such as Proteobacteria. The abundance of the NarG, NirK, and NirS functional genes suggested that the HRT =3 h group had a significant advantage in the nitrate and nitrite reduction phases. Under a short HRT, the composite carbon source achieved a good denitrification effect.

The oncogenic roles of GPR176 in ovarian cancer: a molecular target for aggressiveness and gene therapy.

BACKGROUND: At present, the discovery of new biomarkers is of great significance for the early diagnosis, treatment and prognosis assessment of ovarian cancer. Previous findings indicated that aberrant G-protein-coupled receptor 176 (GPR176) expression might contribute to tumorigenesis and subsequent progression. However, the expression of GPR176 and the molecular mechanisms in ovarian cancer had not been investigated. METHODS: GPR176 expression was compared with clinicopathological features of ovarian cancer using immunohistochemical and bioinformatics analyses. GPR176-related genes and pathways were analysed using bioinformatics analysis. Additionally, the effects of GPR176 on ovarian cancer cell phenotypes were investigated. RESULTS: GPR176 expression positively correlated with elder age, clinicopathological staging, tumour residual status, and unfavourable survival of ovarian cancer, but negatively with purity loss, infiltration of B cells, and CD8+ T cells. Gene Set Enrichment Analysis showed that differential expression of GPR176 was involved in focal adhesion, ECM-receptor interaction, cell adhesion molecules and so on. STRING and Cytoscape were used to determine the top 10 nodes. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that GPR176-related genes were involved in the ECM structural constituent and organisation and so on. GPR176 overexpression promoted the proliferation, anti-apoptosis, anti-pyroptosis, migration and invasion of ovarian cancer cells with overexpression of N-cadherin, Zeb1, Snail, Twist1, and under-expression of gasdermin D, caspase 1, and E-cadherin. CONCLUSION: GPR176 might be involved in the progression of ovarian cancer. It might be used as a biomarker to indicate the aggressive behaviour and poor prognosis of ovarian cancer and a target of genetic therapy.

Ovarian cancer is a gynecological cancer with high mortality. Due to the limited screening tests and treatments available, most ovarian cancer patients are diagnosed at a late stage and the prognosis is poor. The addition of new cancer diagnostic biomarkers and new intervention targets may improve quality of life and survival for patients with ovarian cancer. Previous studies have revealed the aberrant GPR176 expression might contribute to tumorigenesis and subsequent progression in many other tumours. In our study, GPR176 was found to promote the proliferation, anti-apoptosis, anti-pyroptosis, migration and invasion, EMT, and weakening the cellular adhesion of ovarian cancer cells, and involved in the Bcl-2/Bax or the PI3K/Akt/mTOR pathway. Therefore, abnormal expression of GPR176 might be served as a biomarker for aggressive behaviour and poor prognosis of ovarian cancer and a target for gene therapy.

Coastal ecological security assessment in Laizhou Bay, China: from the perspective of demographic-social-economic-natural complex ecosystem.

Assessment of ecological security is essential for understanding the status of bay ecosystem and developing appropriate management strategy. Based on the driving force-pressure-state-impact-response (DPSIR) model, the demographic, economic, social, and ecological data of Laizhou Bay and its three neighboring counties were selected for the period from 2015 to 2021. An ecological security evaluation index system of Laizhou Bay containing 26 indicators was established, and the weights of each indicator were determined by the methods of AHP and EWM, and a comprehensive evaluation of the ecological security of Laizhou Bay was carried out by ESI. Correlations between indicators were analyzed by the Spearman's rank coefficient of correlation. The results showed that there were significant correlations between marine conditions and indicators such as population size in the surrounding area, mariculture area, industrial and domestic wastewater discharge, and treatment rate. Overall, from 2015 to 2021, the ecological security of Laizhou Bay showed a favorable trend, from a relatively unsafe level to a generally safe level, and then to a relatively safe level. Through the comprehensive evaluation of the ecological security of Laizhou Bay, we can recognize the utilization of marine resources and ecological carrying capacity, guide the rational development and utilization of marine resources, and promote the sustainable development of the marine economy.

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.

Hernandezine promotes cancer cell apoptosis and disrupts the lysosomal acidic environment and cathepsin D maturation.

Hernandezine (Her), a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum, is recognized for its range of biological activities inherent to this herbal medicine. Despite its notable properties, the anti-cancer effects of Her have remained largely unexplored. In this study, we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis mechanisms. Furthermore, Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems, leading to LC3 lipidation. Our findings revealed that Her caused damage to the mitochondrial membrane, with the damaged mitochondria undergoing mitophagy, as evidenced by the elevated expression of mitophagy markers. Conversely, Her disrupted autophagic flux, demonstrated by the upregulation of p62 and accumulation of autolysosomes, as observed in the RFP-GFP-LC3 reporter assay. Initially, we determined that Her did not prevent the fusion of autophagosomes and lysosomes. However, it inhibited the maturation of cathepsin D and increased lysosomal pH, indicating an impairment of lysosomal function. The use of the early-stage autophagy inhibitor, 3-methyladenine (3-MA), did not suppress LC3II, suggesting that Her also induces noncanonical autophagy in autophagosome formation. The application of Bafilomycin A1, an inhibitor of noncanonical autophagy, diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her, thereby augmenting Her-induced cell death. These observations imply that while autophagy initially plays a protective role, the disruption of the autophagic process by Her promotes programmed cell death. This study provides the first evidence of Her's dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell death. These insights contribute to a deeper understanding of the mechanisms underlying programmed cell death, offering potential avenues for enhancing cancer prevention and therapeutic strategies.

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.

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.

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.

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.

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.

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.

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.

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.

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.