Nr5a2 ensures inner cell mass formation in mouse blastocyst.

Recent studies have elucidated Nr5a2's role in activating zygotic genes during early mouse embryonic development. Subsequent research, however, reveals that Nr5a2 is not critical for zygotic genome activation but is vital for the gene program between the 4- and 8-cell stages. A significant gap exists in experimental evidence regarding its function during the first lineage differentiation's pivotal period. In this study, we observed that approximately 20% of embryos developed to the blastocyst stage following Nr5a2 ablation. However, these blastocysts lacked inner cell mass (ICM), highlighting Nr5a2's importance in first lineage differentiation. Mechanistically, using RNA sequencing and CUT&Tag, we found that Nr5a2 transcriptionally regulates ICM-specific genes, such as Oct4, to establish the pluripotent network. Interference with or overexpression of Nr5a2 in single blastomeres of 2-cell embryos can alter the fate of daughter cells. Our results indicate that Nr5a2 works as a doorkeeper to ensure ICM formation in mouse blastocyst.

Network Meta-Analysis Indicates Superior Effects of Omega-3 Polyunsaturated Fatty Acids in Preventing the Transition to Psychosis in Individuals at Clinical High-Risk.

BACKGROUND: The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate the efficacy of pharmacological and nutritional interventions in CHR-P and whether these interventions can enhance the efficacy of psychological treatments. METHODS: We systematically reviewed data from 5 databases until July 24, 2021: PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, and WanFang Data. The primary outcome was the transition to psychosis. Network meta-analyses were conducted at 3 time points (6, 12, and ≥24 months) considering both pharmacological/nutritional interventions alone and its combination with psychotherapy. RESULTS: Out of 11 417 identified references, 21 studies were included, comprising 1983 participants. CHR-P participants receiving omega-3 polyunsaturated fatty acids treatment were associated with a lower probability of transition compared with placebo/control at 6 months (odds ratio [OR] = 0.07, 95% confidence interval [CI] = .01 to .054), 12 months (OR = 0.14, 95% CI = .03 to .66), and ≥24 months (OR = 0.16, 95% CI = .05 to .54). Moreover, risperidone plus psychotherapy was associated with a lower likelihood of transition at 6 months compared with placebo/control plus psychotherapy, but this result was not sustained over longer durations. CONCLUSION: Omega-3 polyunsaturated fatty acids helped in preventing transitions to psychosis compared with controls. PROSPERO REGISTRATION NUMBER: CRD42021256209.

Protists play important roles in the assembly and stability of denitrifying bacterial communities in copper-tailings drainage.

Unraveling the drivers controlling the assembly and stability of functional communities is a central issue in ecology. Despite extensive research and data, relatively little attention has been paid on the importance of biotic factors and, in particular, on the trophic interaction for explaining the assembly of microbial community. Here, we examined the diversity, assembly, and stability of nirS-, nirK-, and nosZ-type denitrifying bacterial communities in copper-tailings drainages of the Shibahe tailings reservoir in Zhongtiao Mountain, China's. We found that components of nirS-, nirK-, and nosZ-type denitrifying bacterial community diversity, such as taxon relative abundance, richness, and copy number, were strongly correlated with protist community composition and diversity. Assembly of the nirK-type denitrifying bacterial community was governed by dispersal limitation, whereas those of nirS- and nosZ-type communities were controlled by homogeneous selection. The relative importance of protist diversity in the assembly of nirK- and nosZ-type denitrifying bacterial communities was greater than that in nirS-type assembly. In addition, protists reduced the stability of the co-occurrence network of the nosZ-type denitrifying bacterial community. Compared with eukaryotic algae, protozoa had a greater impact on the stability of denitrifying bacterial community co-occurrence networks. Generally, protists affected the assembly and community stability of denitrifying bacteria in copper-tailings drainages. Our findings thus emphasize the importance of protists on affecting the assembly and community stability of denitrifying bacteria in copper-tailings drainages and may be useful for predicting changes in the ecological functions of microorganisms.

Integrated proteomics and phosphoproteomics profiling reveals the cardioprotective mechanism of bioactive compounds derived from Salvia miltiorrhiza Burge.

BACKGROUND: Natural products are an important source for discovering novel drugs due to their various pharmacological activities. Salvia miltiorrhiza Burge (Danshen) has been shown to have promising therapeutic potential in the management of heart diseases, making it a candidate for cardiovascular drug discovery. Currently, there is limited quantitative analysis of the phosphorylation levels of Danshen-derived natural products on a proteome-wide, which may bias the study of their mechanisms of action. PURPOSE: This study aimed to evaluate the global signaling perturbation induced by Danshen-derived bioactive compounds and their potential relationship with myocardial ischemia/reperfusion (IR) injury therapy. STUDY DESIGN: We employed quantitative proteome and phosphoproteome analysis to identify dysregulated signaling in IR injury hearts from mice. We compared changes induced by Danshen-derived compounds based on IR-associated phospho-events, using an integrative approach that maps relative abundance of proteins and phosphorylation sites. METHODS: Isobaric chemical tandem mass tags (TMT) labeled multiplexing strategy was used to generate unbiased quantitative proteomics and phosphoproteomics data. Highly accurate and precise TMT quantitation was performed using the Orbitrap Fusion Tribrid Mass Spectrometer with synchronous precursor selection MS3 detection mode. Mass spectrometric raw files were analyzed with MaxQuant (2.0.1.0) and statistical and bioinformatics analysis was conducted with Perseus (1.6.15). RESULTS: We quantified 3661 proteins and over 11,000 phosphosites in impaired heart tissue of the IR mice model, expanding our knowledge of signaling pathways and other biological processes disrupted in IR injury. Next, 1548 and 5545 differently expressed proteins and phosphosites were identified by quantifying the proteome and phosphoproteome of H9c2 cells treated by five Danshen bioactive compounds respectively. Results revealed the vast differences in abilities of five Danshen-derived bioactive compounds to regulate phosphorylation modifications in cardiomyocytes, with dihydrotanshinone I (DHT) showing potential for protecting against IR injury by modulating the AMPK/mTOR signaling pathway. CONCLUSIONS: This study provides a new strategy for analyzing drug/natural product-regulated phosphorylation modification levels on a proteome-wide scale, leading to a better understanding of cell signaling pathways and downstream phenotypic responses.

[Diversity Patterns and Influencing Factors of Epibiotic in Vallisneria natans and Planktonic Bacteria Communities].

Planktonic and epiphytic bacterial communities play an important role in wetland nitrogen pollutant removal and water purification, yet their community dynamics are far from understood compared with those of the wetland soil bacterial community. Taking the planktonic bacterial community in the Yuguqiao constructed wetland and the epiphytic bacterial community on the leaf surface of the common submerged plant Vallisneria natans as the research objects, the composition, structure, and functional diversity of planktonic and epiphytic bacterial communities were analyzed using high-throughput sequencing. The results showed that the compositions of the planktonic and epiphytic bacterial communities were significantly different, with more heterotrophic and denitrifying bacteria present in the epiphytic bacterial community than in the planktonic bacterial community. The α diversity of the planktonic bacterial community was significantly different among the three sampling sites but not in the epiphytic bacterial community. In general, the OTU index and Shannon index of the epiphytic bacterial community were significantly higher than those of the planktonic bacterial community, and they had obvious spatial heterogeneity. RDA analysis showed that DO, IC, TP, NH+4, and TOC had important effects on the structural changes of both planktonic and epiphytic bacterial communities but had a greater impact on planktonic bacterial communities. Co-occurrence network analysis showed that the epiphytic bacterial community had more niche differentiation, a more stable network, and stronger resistance to external disturbance. The results of FAPROTAX functional prediction analysis showed that the nitrogen cycling, especially denitrification of the epiphytic bacterial community, was significantly greater than that of the planktonic bacterial community. The results of this study revealed the driving mechanism for maintaining the diversity of planktonic and epiphytic bacterial communities, which can provide a scientific basis for excavating and utilizing planktonic and epiphytic bacterial community resources in the construction of constructed wetlands to improve the efficiency of water purification.

Ecological Processes of Bacterial and Fungal Communities Associated with Typha orientalis Roots in Wetlands Were Distinct during Plant Development.

Root-associated microbiomes are essential for the ecological function of the root system. However, their assembly mechanisms in wetland are poorly understood. In this study, we explored and compared the ecological processes of bacterial and fungal communities in water, bulk soil, rhizosphere soil, and root endosphere niches for 3 developmental stages of Typha orientalis at different wetland sites, and assessed the potential functions of root endosphere microbiomes with function prediction. Our findings suggest that the microbial diversity, composition, and interaction networks along the water-soil-plant continuum are shaped predominantly by compartment niche and developmental stage, rather than by wetland site. Source tracking analysis indicated that T. orientalis' root endosphere is derived primarily from the rhizosphere soil (bacteria 39.9%, fungi 27.3%) and water (bacteria 18.9%, fungi 19.1%) niches. In addition, we found that the assembly of bacterial communities is driven primarily by deterministic processes and fungal communities by stochastic processes. The interaction network among microbes varies at different developmental stages of T. orientalis, and is accompanied by changes in microbial keystone taxa. The functional prediction data supports the distribution pattern of the bacterial and fungal microbiomes, which have different ecological roles at different plant developmental stages, where more beneficial bacterial taxa are observed in the root endosphere in the early stages, but more saprophytic fungi in the late stages. Our findings provide empirical evidence for the assembly, sources, interactions, and potential functions of wetland plant root microbial communities and have significant implications for the future applications of plant microbiomes in the wetland ecosystem. IMPORTANCE Our findings provide empirical evidence for the assembly, sources, interactions, and potential functions of wetland plant root microbial communities, and have significant implications for the future applications of plant microbiomes in the wetland ecosystem.

Proteomics analysis uncovers plasminogen activator PLAU as a target of the STING pathway for suppression of cancer cell migration and invasion.

The stimulator of interferon genes (STING) pathway is vital for immune defense against pathogen invasion and cancer. Although ample evidence substantiates that the STING signaling pathway plays an essential role in various cancers via cytokines, no comprehensive investigation of secretory proteins regulated by the STING pathway has been conducted hitherto. Herein, we identify 24 secretory proteins significantly regulated by the STING signaling pathway through quantitative proteomics. Mechanistic analyses reveal that STING activation inhibits the translation of urokinase-type plasminogen activator (PLAU) via the STING-PERK-eIF2α signaling axis. PLAU is highly expressed in a variety of cancers and promotes the migration and invasion of cancer cells. Notably, the activation of STING inhibits cancer cell migration and invasion by suppressing PLAU. Collectively, these results provide novel insights into the anticancer mechanism of the STING pathway, offering a theoretical basis for precision therapy for this patient population.

Bacterial Community Spacing Is Mainly Shaped by Unique Species in the Subalpine Natural Lakes of China.

Bacterial communities have been described as early indicators of both regional and global climatic change and play a critical role in the global biogeochemical cycle. Exploring the mechanisms that determine the diversity patterns of bacterial communities and how they share different habitats along environmental gradients are, therefore, a central theme in microbial ecology research. We characterized the diversity patterns of bacterial communities in Pipahai Lake (PPH), Mayinghai Lake (MYH), and Gonghai Lake (GH), three subalpine natural lakes in Ningwu County, Shanxi, China, and analyzed the distribution of their shared and unique taxa (indicator species). Results showed that the species composition and structure of bacterial communities were significantly different among the three lakes. Both the structure of the entire bacterial community and the unique taxa were significantly influenced by the carbon content (TOC and IC) and space distance; however, the structure of the shared taxa was affected by conductivity (EC), pH, and salinity. The structure of the entire bacterial community and unique taxa were mainly affected by the same factors, suggesting that unique taxa may be important in maintaining the spatial distribution diversity of bacterial communities in subalpine natural freshwater lakes. Our results provide new insights into the diversity maintenance patterns of the bacterial communities in subalpine lakes, and suggest dispersal limitation on bacterial communities between adjacent lakes, even in a small local area. We revealed the importance of unique taxa in maintaining bacterial community structure, and our results are important in understanding how bacterial communities in subalpine lakes respond to environmental change in local habitats.

Achieving rapid thiosulfate-driven denitrification (TDD) in a granular sludge system.

Sulfur-oxidizing bacteria (SOB) can drive a high level of autotrophic denitrification (AD) activity with thiosulfate (S2O32-) as the electron donor. However, the slow growth of SOB results in a low biomass concentration in the AD reactor and unsatisfactory biological nitrogen removal (BNR). In this study, our goal was to establish a high-rate thiosulfate-driven denitrification (TDD) system via sludge granulation. Granular sludge was successfully cultivated by increasing the nitrogen loading rate stepwise in thiosulfate-oxidizing/nitrate-reducing conditions in an upflow anaerobic blanket reactor. In the mature-granular-sludge reactor, a nitrate removal rate of 280 mg N/L/h was achieved with a nitrate removal efficiency of 97.7%±1.0% at a hydraulic retention time of only 15 minutes, with no nitrite detected in the effluent. Extracellular polymeric substance (EPS) analysis indicated that the proteins in loosely bound and tightly bound EPS were responsible for maintaining the compact structure of the TDD granular sludge. The dynamics of the microbial-community shift were identified by 16S rRNA high-throughput pyrosequencing analysis. The Sulfurimonas genus was found to be enriched at 74.1% of total community and may play the most critical role in the high-rate BNR. The batch assay results reveal that no nitrite accumulation occurred during nitrate reduction because the nitrate reduction rate (75.90±0.67 mg N/g MLVSS/h) was almost equal to the nitrite reduction rate (66.06±1.28 mg N/g MLVSS/h) in the thiosulfate-driven granular sludge reactor. The results of this study provide support for the establishment of a high-rate BNR system that maintains its stability with a low sludge yield.

Circulating lncRNA ABHD11-AS1 serves as a biomarker for early pancreatic cancer diagnosis.

Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening.

GLS1 promotes proliferation in hepatocellular carcinoma cells via AKT/GSK3ß/CyclinD1 pathway.

Glutamine metabolism is an important metabolic pathway for cancer cell survival, and there is a critical connection between tumor growth and glutamine metabolism. However, the role of GLS1 in hepatocellular carcinoma (HCC) progression remains to be elucidated. In this study, we reported that GLS1 expression was significantly increased in HCC tissues and correlated with serum AFP, tumor differentiation, lymphatic metastasis, TNM stage, and poorer patient outcome. We further showed that GLS1 promoted colony formation and cell proliferation of HCC cells. Furthermore, our data showed that GLS1 inhibitor compound 968 inhibited the proliferation of HCC cells in a dose-dependent manner. Importantly, we found that GLS1 overexpression increased p-AKT, p-GSK3ß and cyclinD1 expression, and had no influence on total AKT and GSK3ß protein level, indicating that GLS1 was involved in AKT/GSK3ß/CyclinD1 pathway. It is suggested that GLS1 promotes proliferation in HCC cells probably via AKT/GSK3ß/CyclinD1 pathway and may be a potential target for anti-hepatocellular carcinoma cancer.

LncRNA UCA1 promotes migration and invasion in pancreatic cancer cells via the Hippo pathway.

Although overexpression of the long non-coding RNA (lncRNA) UCA1 has been implicated in several human cancers, its biological function in pancreatic cancer remains to be clarified. In this study, we reported that UCA1 expression was significantly increased in pancreatic cancer tissues and correlated with clinicopathological features, tumor stage, and poorer patient outcome. We further showed that UCA1 promoted cell migration and invasion of pancreatic cancer cells. Importantly, we found that UCA1 overexpression inhibited YAP phosphorylation, and increased YAP expression. Mechanistically, UCA1 interacted with MOB1, Lats1, and YAP, forming shielding composites. Moreover, we demonstrated that UCA1 increased YAP nuclear localization and stabilization, and improved TEAD luciferase activity. In turn, YAP promotes UCA1 expression. Collectively, the present study provides insights into the mechanistic regulation of UCA1 promoting pancreatic cancer progression through the Hippo signaling pathway. UCA1 may serve as a candidate biomarker for poor prognosis and a target for new pancreatic cancer therapies.

Protein arginine methyltransferase 1 coordinates the epithelial-mesenchymal transition/proliferation dichotomy in gastric cancer cells.

Protein arginine methyltransferase 1 (PRMT1) is up-regulated and promotes migration, invasion and proliferation in wide range of cancers. However, we for the first time identify that PRMT1 promotes migration and invasion and inhibits proliferation in gastric cancer cells, a phenomenon called "migration-proliferation dichotomy". First, we find that PRMT1 overexpression promotes migration and invasion and inhibits proliferation, whereas PRMT1 knockdown reverses the above abilities. Next, PRMT1 reduces the expression of epithelial marker E-cadherin and increases the expression of mesenchymal markers including N-cadherin, Vimentin, snail and ß-catenin in gastric cancer cells. Furthermore, our studies show that PRMT1 silencing promotes the phosphorylation of LATS1, and then induces YAP phosphorylation, while overexpression of PRMT1 down-regulates the phosphorylation of LATS1 and YAP, indicating that PRMT1 inhibits EMT probably via Hippo signaling. Collectively, the present study reveals important roles of PRMT1 in progression of gastric cancer. Given the dual functions of PRMT1, it is as a potential drug target of gastric cancer with extreme caution.