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Environmental heterogeneity in cold seeps is usually reflected by different faunal aggregates. The sediment microbiome, especially the geochemical cycling-associated communities, sustains the ecosystem through chemosynthesis. To date, few studies have paid attention to the structuring and functioning of geochemical cycling-associated communities relating to environmental heterogeneity in different faunal aggregates of cold seeps. In this study, we profiled the microbial community of four faunal aggregates in the Haima cold seep, South China Sea. Through a combination of geochemical and meta-omics approaches, we have found that geochemical variables, such as sulfate and calcium, exhibited a significant variation between different aggregates, indicating changes in the methane flux. Anaerobic methanotrophic archaea (ANME), sulfate-reducing, and sulfide-oxidizing bacteria (SRB and SOB) dominated the microbial community but varied in composition among the four aggregates. The diversity of archaea and bacteria exhibited a strong correlation between sulfate, calcium, and silicate. Interspecies co-exclusion inferred by molecular ecological network analysis increased from non-seep to clam aggregates and peaked at the mussel aggregate. The networked geochemical cycling-associated species showed an obvious aggregate-specific distribution pattern. Notably, hydrocarbon oxidation and sulfate reduction by ANME and SRB produced carbonate and sulfide, driving the alkalization of the sediment environment, which may impact the microbial communities. Collectively, these results highlighted that geofluid and microbial metabolism together resulted in environmental heterogeneity, which shaped the C and S cycling-associated microbial community.

Marine oil spills are a significant concern worldwide, destroying the ecological environment and threatening the survival of marine life. Various oil-degrading bacteria have been widely reported in marine environments in response to marine oil pollution. However, little information is known about culturable oil-degrading bacteria in cold seep of the deep-sea environments, which are rich in hydrocarbons. This study enriched five oil-degrading consortia from sediments collected from the Haima cold seep areas of the South China Sea. Parvibaculum, Erythrobacter, Acinetobacter, Alcanivorax, Pseudomonas, Marinobacter, Halomonas, and Idiomarina were the dominant genera. Further results of bacterial growth and degradation ability tests indicated seven efficient alkane-degrading bacteria belonging to Acinetobacter, Alcanivorax, Kangiella, Limimaricola, Marinobacter, Flavobacterium, and Paracoccus, whose degradation rates were higher in crude oil (70.3–78.0%) than that in diesel oil (62.7–66.3%). From the view of carbon chain length, alkane degradation rates were medium chains > long chains > short chains. In addition, Kangiella aquimarina F7, Acinetobacter venetianus F1, Limimaricola variabilis F8, Marinobacter nauticus J5, Flavobacterium sediminis N3, and Paracoccus sediminilitoris N6 were first identified as oil-degrading bacteria from deep-sea environments. This study will provide insight into the bacterial community structures and oil-degrading bacterial diversity in the Haima cold seep areas, South China Sea, and offer bacterial resources to oil bioremediation applications.

BackgroundTreatment-resistant auditory verbal hallucinations (TRAVHs) might cause an increased risk of violence, suicide, and hospitalization in patients with schizophrenia (SCZ). Although neuroimaging studies have identified the neural correlation to the symptom of AVH, functional brain activity that correlates particularly in patients with TRAVH remains limited. Functional near-infrared spectroscopy (fNIRS) is a portable and suitable measurement, particularly in exploring brain activation during related tasks. Hence, our researchers aimed to explore the differences in the cerebral hemodynamic function in SCZ-TRAVH, patients with schizophrenia without AVH (SCZ-nAVH), and healthy controls (HCs), to examine neural abnormalities associated more specifically with TRAVH.MethodsA 52-channel functional near-infrared spectroscopy system was used to monitor hemodynamic changes in patients with SCZ-TRAVH (n = 38), patients with SCZ-nAVH (n = 35), and HC (n = 30) during a verbal fluency task (VFT). VFT performance, clinical history, and symptom severity were also noted. The original fNIRS data were analyzed using MATLAB to obtain the β values (the brain cortical activity response during the VFT task period); these were used to calculate Δβ (VFT β minus baseline β), which represents the degree of change in oxygenated hemoglobin caused by VFT task.ResultOur results showed that there were significant differences in Δβ values among the three groups at 26 channels (ch4, ch13-15, 18, 22, ch25–29, 32, ch35–39, ch43–51, F = 1.70 to 19.10, p < 0.043, FDR-corrected) distributed over the prefrontal–temporal cortical regions. The further pairwise comparisons showed that the Δβ values of 24 channels (ch13–15, 18, 22, 25, ch26–29, ch35–39, ch43–49, ch50–51) were significantly lower in the SCZ group (SCZ-TRAVH and/or SCZ-nAVH) than in the HC group (p < 0.026, FDR-corrected). Additionally, the abnormal activation in the ch22 of right postcentral gyrus was correlated, in turn, with severity of TRAVH.ConclusionOur findings indicate that specific regions of the prefrontal cortex may be associated with TRAVH, which may have implications for early intervention for psychosis.

Reef-building corals are invertebrate animals that associate with diverse microorganisms, including Symbiodiniaceae, bacteria, fungi, and archaea. This symbiotic consortium, called the holobiont, is a dynamic system and rapidly responds to environmental temperatures. At present, the effects of temperature on bacteria-bacteria interactions in the coral-associated bacterial community are not clear. Antagonism is considered one of the potential structuring forces in coral microbial communities. Here, we examined the antagonistic interactions among 32 coral-associated bacteria and the physiological and biochemical characteristics of these isolates at different temperatures. The results showed that the antagonism breadth (i.e. the total number of antagonistic interactions) increased but antagonism intensity (i.e. the size of the inhibition zone) decreased at 32°C. The antagonistic interaction network was nested and sender-determined both at 25°C and 32°C, suggesting that the competition networks of coral-associated bacteria were more influenced by the antagonist strains than sensitive strains. Furthermore, we found that the elevated temperature increased the complexity of the antagonistic network. By evaluating the correlations between antagonism and the phylogenetic and phenotypic distances, we demonstrated that the antagonism probability correlated with the phylogenetic distance rather than phenotypic distance. Moreover, the antagonist strains have a wider metabolic niche space, i.e., grew on more carbon sources, than the antagonized strains at 25°C, while there was no difference at 32°C, suggesting the trade-off between antagonism and resource exploitation shifted in the antagonistic interactions under the higher temperature. These findings will be helpful for understanding the bacterial interactions in coral holobionts and the assembly of bacterial community in altered environments, especially under heat stress.

Diagnosis and treatment of the patients with major depression (MD) or the combined anxiety and depression (A&D) depend on the questionnaire, sometimes accompanied by tasks such as verbal fluency task (VFT). Functional near infrared spectroscopy (fNIRS) is emerging as an auxiliary diagnostic tool to evaluate brain function, providing an objective criterion to judge psychoses. At present, the conclusions derived from VFT or rest (non-task) studies are controversial. The purpose of this study is to evaluate if task performs better than non-task in separating healthy people from psychiatric patients. In this study, healthy controls (HCs) as well as the patients with MD or A&D were recruited (n = 10 for each group) to participate in the non-task and VFT tasks, respectively, and the brain oxygenation was longitudinally evaluated by using fNIRS. An approach of spectral analysis is used to analyze cerebral hemoglobin parameters (i.e., Oxy and Deoxy), characterizing the physiological fluctuations in the non-task and task states with magnitude spectrum and average power. Moreover, the standard deviation of oxygenation responses during the non-task was compared with the peak amplitude during the task, with the aim to explore the sensitivity of the VFT task to brain activation. The results show that there is no significant difference (p > 0.05) among the three groups in average power during non-task. The VFT task greatly enhanced the magnitude spectrum, leading to significant difference (p < 0.05) in average power between any of two groups (HC, MD, and A&D). Moreover, 40% patients with A&D have an intermediate peak (around 0.05 Hz) in the magnitude spectrum when performing the VFT task, indicating its advantage in characterizing A&D. We defined a rate of the non-task standard variation to the task peak amplitude (namely, SD-to-peak rate) and found that this rate is larger than 20% in 90% of the MD subjects. By contrast, only 40% HC subjects have an SD-to-peak rate larger than 20%. These results indicate that the non-task may not be sufficient to separate MD or A&D from HC. The VFT task could enhance the characteristics of the magnitude spectrum, but its intensity needs to be elevated so as to properly explore brain functions related to psychoses.

Anxiety and depression are widespread psychosis which are believed to affect cerebral metabolism, especially in frontal and temporal cortex. The comorbidity patients of anxiety and depression (A&D) have more serious clinical symptoms. Functional near-infrared spectroscopy (fNIRS) is a noninvasive modality used to monitor human brain oxygenation, and it could be considered as a potential tool to detect psychosis which may lead to abnormal cerebral oxygen status when the brain is activated. However, how sensitive the cerebral oxygenation response to the cortex activation and whether these responses are consistent at different stages of A&D or different regions still remains unclear. In this study, a conventional physiological paradigm for cortex activation, i.e., verbal fluency task (VFT), and a relatively new paradigm, i.e., high-level cognition task (HCT), were compared to detect A&D through a longitudinal measurement of cerebral oxygen status by fNIRS. The A&D patients at the acute, consolidation and maintenance stages as well as the healthy subjects participated in the VFT and HCT paradigms, respectively. For the VTF paradigm, the subject was instructed to answer questions of phrase constructions within 60 s. For the HCT paradigm, the subject was instructed to categorize items, logical reasoning, and comprehensive judgment and write down the answers within 60 s. For most of the subjects, the oxy-Hb is found to increase remarkably, accompanied with a relatively small reduction in deoxy-Hb when subject to both paradigms. The statistical analyses show a relatively large variability within any group, leading to the significant difference that was only found between A&D at the acute stage and healthy subjects in the temporal lobe region (p < 0.001). Nevertheless, HCT would activate more oxygen increment when compared with the VFT, with a large integral value in oxy-Hb. On average, the oxy-Hb integral value of the A&D patients differs substantially at different stages when subject to HCT paradigm. Moreover, the prefrontal lobe and temporal lobe responses were more consistent to the HCT paradigm rather than the VFT paradigm. Under the VFT paradigm, however, no remarkable difference in integral value was found among the three stages, either at the prefrontal lobe or at the temporal lobe. This study indicated that HCT, which is intensively involved in brain function, would activate more oxygenation changes in the cerebral cortex. Additionally, with good performance at distinguishing different stages according to the oxy-Hb criterion, the HCT has the potential to evaluate the therapeutic effects for A&D patients.

Liver cancer is associated with high mortality, particularly in patients infected with the hepatitis B virus. Treatment methods remain very limited. Here, we explored the effects of 17β-estradiol (E2) on apoptosis of various liver cell lines (LO2, HepG2, and HepG2.2.15 cells). Within a certain concentration range, 17β-estradiol induced oxidative stress and apoptosis of HepG2 cells, downregulated ERα-36 expression, and increased Akt and Foxo3a phosphorylation. p-Foxo3a became localized around the nucleus but did not enter the organelle. The levels of mRNAs encoding manganese superoxide dismutase (MnSOD) and catalase, to the promoters of which Foxo3a binds to trigger gene expression, were significantly reduced in HepG2 cells. 17β-estradiol had no obvious effects on LO2 or HepG2.2.15 cells. We speculate that 17β-estradiol may induce oxidative stress in HepG2 cells by increasing Foxo3a phosphorylation, thus promoting apoptosis. This may serve as a new treatment for hepatocellular carcinoma.

NORFA, the first lincRNA associated with sow fertility, has been shown to control granulosa cell (GC) functions and follicular atresia. However, the underlying mechanism is not fully understood. In this study, RNA-seq was performed and we noticed that inhibition of NORFA led to dramatic transcriptomic alterations in porcine GCs. A total of 1,272 differentially expressed transcripts were identified, including 1167 DEmRNAs and 105 DEmiRNAs. Furthermore, protein–protein interaction, gene-pathway function, and TF–miRNA–mRNA regulatory networks were established and yielded four regulatory modules with multiple hub genes, such as AR, ATG5, BAK1, CENPE, NR5A1, NFIX, WNT5B, ssc-miR-27b, and ssc-miR-126. Functional assessment showed that these hub DEGs were mainly enriched in TGF-β, PI3K-Akt, FoxO, Wnt, MAPK, and ubiquitin pathways that are essential for GC states (apoptosis and proliferation) and functions (hormone secretion). In vitro, we also found that knockdown of NORFA in porcine GCs significantly induced cell apoptosis, impaired cell viability, and suppressed 17β-estradiol (E2) synthesis. Notably, four candidate genes for sow reproductive traits (INHBA, NCOA1, TGFβ-1, and TGFBR2) were also identified as potential targets of NORFA. These findings present a panoramic view of the transcriptome in NORFA-reduced GCs, highlighting that NORFA, a candidate lincRNA for sow fertility, is crucial for the normal states and functions of GCs.

In this work, a solid polymer electrolyte (SPE) doped with carbon nanotubes (CNTs) was used as a gas sensing material for a NO2 gas sensor. The electrolytes consisted of the ionic liquids (ILs) and CNTs, which were immobilized in a poly(vinylidene fluoride) (PVDF) matrix. The SPE membranes were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FTIR), and cyclic voltammetry (CV). The experimental results show that the addition of an appropriate amount of CNTs can appropriately improve the electrochemical performance of the SPE membrane. It was shown that NO2 gas sensors with an appropriate amount of CNTs added to their SPEs had a higher gas sensitivity than those with SPE containing no CNTs. When the mass ratio of PVDF, N-methyl-2-pyrrolidone (NMP), IL, and CNT was 1:4:1:0.08, the SPE showed the best gas sensitivity, and its sensitivity is 0.00275 V/ppm.

The harsh environment such as high temperature greatly limits the growth, development and production of crops worldwide. NAC (NAM, ATAF1/2, and CUC2) transcription factors (TFs) play key regulatory roles in abiotic stress responses of plants. However, the functional roles of NAC TFs in heat stress response of maize remain elusive. In our present study, we identified and isolated a stress-responsive NAC transcription factor gene in maize, designated as ZmNAC074 and orthologous with rice OsNTL3. Further studies revealed that ZmNAC074 may encode a membrane-bound transcription factor (MTF) of NAC family in maize, which is comprised of 517 amino acid residues with a transmembrane domain at the C-terminus. Moreover, ZmNAC074 was highly expressed and induced by various abiotic stresses in maize seedlings, especially in leaf tissues under heat stress. Through generating ZmNAC074 transgenic plants, phenotypic and physiological analyses further displayed that overexpression of ZmNAC074 in transgenic Arabidopsis confers enhanced heat stress tolerance significantly through modulating the accumulation of a variety of stress metabolites, including reactive oxygen species (ROS), antioxidants, malondialdehyde (MDA), proline, soluble protein, chlorophyll and carotenoid. Further, quantitative real-time PCR analysis showed that the expression levels of most ROS scavenging and HSR- and UPR-associated genes in transgenic Arabidopsis were significantly up-regulated under heat stress treatments, suggesting that ZmNAC074 may encode a positive regulator that activates the expression of ROS-scavenging genes and HSR- and UPR-associated genes to enhance plant thermotolerance under heat stress conditions. Overall, our present study suggests that ZmNAC074 may play a crucial role in conferring heat stress tolerance in plants, providing a key candidate regulatory gene for heat stress tolerance regulation and genetic improvement in maize as well as in other crops.

Calcium (Ca2+) is the most abundant divalent cation in plants, and cellular levels of Ca2+, which functions as a nutrient and secondary messenger, play a critical role in plant immunity. In the present study, we found that FERONIA-like receptor 1 (FLR1) positively regulates Magnaporthe oryzae resistance and that expression of FLR1 is strongly induced in response to Ca2+ deficiency. In addition, the Ca content in the shoots of flr1 was lower than that in wild-type, and the M. oryzae-sensitive phenotype of the flr1 mutant was not rescued by exogenous application of Ca2+. Moreover, RNA sequencing revealed 2,697 differentially expressed genes (DEGs) in the flr1 mutant compared with wild-type, and some of these DEGs are involved in cellular metal ion homeostasis and transition metal ion homeostasis. Changes in expression of overlapping genes between the flr1 mutant and in plants under low-Ca2+ treatment were consistent in terms of direction, indicating that FLR1 is involved in Ca2+ homeostasis. In summary, we detected FLR1-mediated resistance to M. oryzae, a phenomenon associated with Ca2+ homeostasis.

Ralstonia solanacearum species complex (RSSC) is a group of Gram-negative bacterial pathogen capable of infecting numerous plants and crops, causing severe vascular wilt diseases. Functional analysis of the genes associated with bacterial virulence is critical for elucidating the molecular mechanisms that govern the bacterial pathogenicity. To this end, an efficient gene deletion method would be of great help. In this study, we set to develop an efficient and simple markerless gene deletion method by exploiting its natural transformation competence and the FLP/FRT recombination system. We found that natural transformation using PCR products provided much higher transformation frequency than the plasmid-based triparental mating and electroporation. We thus generated the gene deletion fusion PCR fragments by incorporating the upstream and downstream DNA fragments of the target gene and an antibiotic resistance gene flanked by FRT sites, and delivered the PCR products into R. solanacearum cells through natural transformation. Using this method, we knocked out the epsB and phcA genes, which are associated with exopolysaccharide (EPS) biosynthesis and regulation, respectively, in several R. solanacearum strains isolated from different host plants at a frequency from 5 (1E-08) to 45 (1E-08). To remove the antibiotic marker gene, the plasmid expressing the FLP enzyme was introduced into the above knockout mutants, which enabled removal of the marker gene. The effective combination of natural transformation and the FLP/FRT recombination system thus offers a simple and efficient method for functional study of putative virulence genes and for elucidation of R. solanacearum pathogenic mechanisms.

Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, β-lactoglobulin (β-LG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of β-LG-specific immunoglobulins E (β-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-κB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8−IFN-γ+ T cells in the spleen increased, while CD3+CD8−IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce β-LG-induced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy.

In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. NAT10 might regulate OGA stability and expression by suppressing its degradation. To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. After knocking down OGA of oocytes, oocyte maturation was inhibited. In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein–coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. Rsph6a, Gm7788, Gm41780, Trpc7, Gm29036, and Gm47144 were potential downstream genes. In conclusion, NAT10 maintained the stability of OGA transcript by ac4C modification on it, thus positively regulating IVM. Moreover, our study revealed the regulation mechanisms of oocytes maturation and provided reference for improving IVM outcomes. At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation.

Hyperuricemia (HUA) is the presence of excessive uric acid (UA) in blood, which leads to an increased risk of chronic kidney disease and gout. Probiotics have the potential effect of alleviating HUA. The purpose of this study was to screen probiotics with UA-lowering activity and explore the underlying mechanism. The UA-lowering activity of 20 lactic acid bacteria strains was investigated in vitro, and the effect of candidate probiotics on UA metabolism was evaluated using the HUA Balb/c mouse model. The results showed that Lactobacillus paracasei X11 had excellent UA-lowering activity in vitro, which could degrade nucleotides and nucleosides completely within 30 min, and the degradation rates of purine and trioxypurine could reach 83.25% and 80.42%, respectively. In addition, oral administration of L. paracasei X11 could reduce serum UA by 52.45% and inhibit renal proinflammatory cytokine IL-1β by 50.69%, regulating adenosine deaminase (ADA), xanthine oxidase (XOD), and transporter expression (GLUT9, NPT1, and URAT1) to a normal level. Moreover, it could restore the ratio of Bacteroidetes to Firmicutes (Bac/Firm ratio) and showed a positive effect on the recovery of the intestinal microbiota. These findings provided fundamental information about the UA-lowering properties of probiotics, which suggested that L. paracasei X11 had the potential to be developed as a novel probiotic strain to ameliorate HUA.

Hyperuricemia (HUA) is a disorder of purine metabolism resulting in abnormally elevated serum uric acid (UA) concentration. It is believed that there is an association between gut microbiota and HUA, and probiotics have the potential palliative effect. However, the underlying mechanism of probiotics in ameliorating HUA remains unclear. The purpose of this study was to investigate the effect and mechanism of Lactobacillus plantarum Q7 on HUA in Balb/c mice. The results showed that L. plantarum Q7 had an excellent capability to affect UA metabolism, which could degrade nucleotides by 99.97%, nucleosides by 99.15%, purine by 87.35%, and UA by 81.30%. It was observed that L. plantarum Q7 could downregulate serum UA, blood urea nitrogen (BUN), creatinine (Cr), and xanthine oxidase (XOD) by 47.24%, 14.59%, 54.59%, and 40.80%, respectively. Oral administration of L. plantarum Q7 could restore the liver, kidney, and intestinal injury induced by HUA and the expression of metabolic enzymes and transporters to normal level. 16S rRNA sequencing analysis showed that L. plantarum Q7 treatment could restore the imbalance of species diversity, richness, and community evenness compared with the model group. The ratio of Bacteroidetes to Firmicutes was recovered nearly to the normal level by L. plantarum Q7 intervention. The dominant microorganisms of L. plantarum Q7 group contained more anti-inflammatory bacteria than those of the model group. These findings indicated that L. plantarum Q7 might regulate UA metabolism and repair the liver and kidney injury by reshaping the gut microbiota and could be used as a potential probiotic strain to ameliorate HUA.

Triple negative breast cancer (TNBC) remains the worst molecular subtype due to high heterogeneity and lack of effective therapeutic targets. Here we investigated the tumor and immune microenvironment heterogeneity of TNBC using scRNA-seq and bulk RNA-seq data from public databases and our cohort. Macrophage subpopulations accounted for a high proportion of tumor immune microenvironment (TIME), and M1 macrophages were associated with better clinical outcomes. Furthermore, three maker genes including IFI35, PSMB9, and SAMD9L showed a close connection with M1 macrophages. Specifically, IFI35 was positively associated with macrophage activation, chemotaxis, and migration. Also, patients with high IFI35 expression had a better prognosis. In vitro studies subsequently demonstrated that IFI35 was upregulated during the M1 subtype differentiation of macrophages. In summary, our data suggested that IFI35 maybe a promising novel target that helps to reshape macrophage polarization towards the M1 subtype for anti-tumor effects.

Probiotics plays an important role in regulating gut microbiota and maintaining intestinal homeostasis. Extracellular vesicles (EVs) derived from probiotics have emerged as potential mediators of host immune response and anti-inflammatory effect. However, the anti-inflammatory effect and mechanism of probiotics derived EVs on inflammatory bowel disease (IBD) remains unclear. In this study, the effect of Lactobacillus plantarum Q7-derived extracellular vesicles (Q7-EVs) on gut microbiota and intestinal inflammation was investigated in C57BL/6J mice. The results showed that Q7-EVs alleviated DSS-induced colitis symptoms, including colon shortening, bleeding, and body weight loss. Consumption of Q7-EVs reduced the degree of histological damage. DSS-upregulated proinflammatory cytokine levels including IL-6, IL-1β, IL-2 and TNF-α were reduced significantly by Q7-EVs (p < 0.05). 16S rRNA sequencing results showed that Q7-EVs improved the dysregulation of gut microbiota and promoted the diversity of gut microbiota. It was observed that the pro-inflammatory bacteria (Proteobacteria) were reduced and the anti-inflammatory bacteria (Bifidobacteria and Muribaculaceae) were increased. These findings indicated that Q7-EVs might alleviate DSS-induced ulcerative colitis by regulating the gut microbiota.

BackgroundTo date, breast cancer remains the primary cause of tumor-related death among women, even though some leap-type developments of oncology have been done to slash the mortality. Considering the tumor heterogeneity and individual variation, the more reliable biomarkers are required to be identified for supporting the development of precision medicine in breast cancer.MethodsBased on the TCGA-BRCA and METABRIC databases, the differently expressed RNA binding proteins (RBPs) between tumor and normal tissues were investigated. In this study, we focused on the communal differently expressed RBPs in four subtypes of breast cancer. Lasso-penalized Cox analysis, Stepwise-multivariate Cox analysis and Kaplan–Meier survival curve were performed to identify the hub RBP-coding genes in predicting prognosis of breast cancer, and a prognostic model was established. The efficiency of this model was further validated in other independent GSE20685, GSE4922 and FUSCC-TNBC cohorts by calculating the risk score and performing survival analysis, ROC and nomogram. Moreover, pathologic functions of the candidate RBPs in breast cancer were explored using some routine experiments in vitro, and the potential compounds targeting these RBPs were predicted by reviewing the Comparative Toxicogenomics Database.ResultsHere, we identified 62 RBPs which were differently expressed between the tumor and normal tissues. Thereinto, three RBPs (MRPL12, MRPL13 and POP1) acted as independent risk factors, and their expression pattern also correlated with poor prognosis of patients. A prognostic model, built with these 3-RBPs, possessed statistical significance to predict the survival probability of patients with breast cancer. Furthermore, experimental validations showed that down-regulating the expression of endogenous MRPL12, MRPL13 or POP1 could dramatically suppress the cellular viability and migration of breast cancer cells in vitro. Besides, some compounds (such as the Acetaminophen, Urethane and Tunicamycin) were predicted for curing breast cancer via targeting MRPL12, MRPL13 and POP1 simultaneously.ConclusionThis study identified and established a 3-RBPs-based signature and nomogram for predicting the survival probability of patients with breast cancer. MRPL12, MRPL13 and POP1 might act as oncogenes in maintaining cellular viability and accelerating metastasis of breast cancer cells, implying the possibility of which to be designed as biomarkers and/or therapeutic targets for breast cancer.

N4-acetylcytidine (ac4C), a newly identified epigenetic modification within mRNA, has been characterized as a crucial regulator of mRNA stability and translation efficiency. However, the role of ac4C during oocyte maturation, the process mainly controlled via post-transcriptional mechanisms, has not been explored. N-acetyltransferase 10 (NAT10) is the only known enzyme responsible for ac4C production in mammals and ac4C-binding proteins have not been reported yet. In this study, we have documented decreasing trends of both ac4C and NAT10 expression from immature to mature mouse oocytes. With NAT10 knockdown mediated by small interfering RNA (siRNA) in germinal vesicle (GV)-stage oocytes, ac4C modification was reduced and meiotic maturation in vitro was significantly retarded. Specifically, the rate of first polar body extrusion was significantly decreased with NAT10 knockdown (34.6%) compared to control oocytes without transfection (74.6%) and oocytes transfected with negative control siRNA (72.6%) (p < 0.001), while rates of germinal vesicle breakdown (GVBD) were not significantly different (p = 0.6531). RNA immunoprecipitation and high-throughput sequencing using HEK293T cells revealed that the modulated genes were enriched in biological processes associated with nucleosome assembly, chromatin silencing, chromatin modification and cytoskeletal anchoring. In addition, we identified TBL3 as a potential ac4C-binding protein by a bioinformatics algorithm and RNA pulldown with HEK293T cells, which may mediate downstream cellular activities. Taken together, our results suggest that NAT10-mediated ac4C modification is an important regulatory factor during oocyte maturation in vitro and TBL3 is a potential ac4C-binding protein.

The acute thermal response has been extensively studied in commercial chickens because of the adverse effects of heat stress on poultry production worldwide. Here, we performed whole-genome resequencing of autochthonous Niya chicken breed native to the Taklimakan Desert region as well as of 11 native chicken breeds that are widely distributed and reared under native humid and temperate areas. We used combined statistical analysis to search for putative genes that might be related to the adaptation of hot arid and harsh environment in Niya chickens. We obtained a list of intersected candidate genes with log2 θπ ratio, FST and XP-CLR (including 123 regions of 21 chromosomes with the average length of 54.4 kb) involved in different molecular processes and pathways implied complex genetic mechanisms of adaptation of native chickens to hot arid and harsh environments. We identified several selective regions containing genes that were associated with the circulatory system and blood vessel development (BVES, SMYD1, IL18, PDGFRA, NRP1, and CORIN), related to central nervous system development (SIM2 and NALCN), related to apoptosis (CLPTM1L, APP, CRADD, and PARK2) responded to stimuli (AHR, ESRRG FAS, and UBE4B) and involved in fatty acid metabolism (FABP1). Our findings provided the genomic evidence of the complex genetic mechanisms of adaptation to hot arid and harsh environments in chickens. These results may improve our understanding of thermal, drought, and harsh environment acclimation in chickens and may serve as a valuable resource for developing new biotechnological tools to breed stress-tolerant chicken lines and or breeds in the future.

The ubiquitous second messenger c-di-GMP is involved in regulation of multiple biological functions including the important extracellular matrix exopolysaccharides (EPS). But how c-di-GMP metabolic proteins influence EPS and their enzymatic properties are not fully understood. Here we showed that deletion of proE, which encodes a protein with GGDEF-EAL hybrid domains, significantly increased the transcriptional expression of the genes encoding EPS production in Pseudomonas aeruginosa PAO1 and changed the bacterial colony morphology. Our data showed that ProE is a very active phosphodiesterase (PDE), with a high enzyme activity in degradation of c-di-GMP. Interestingly, the optimal activity of ProE was found in the presence of Co2+, unlike other PDEs that commonly rely on Mg2+ or Mn2+ for best performance. Furthermore, we identified three widely conserved novel residues that are critical for the function of ProE through site-directed mutagenesis. Subsequent study showed that ProE, together with other three key PDEs, i.e., RbdA, BifA, and DipA regulate the EPS production in P. aeruginosa PAO1. Moreover, by using the GFP-fusion approach, we observed that these four EPS associated-PDEs showed a polar localization pattern in general. Taken together, our data unveil the molecular mechanisms of ProE in regulation of EPS production, and provide a new insight on its enzymatic properties in degradation of c-di-GMP.