Unveiling the efficacy of Bacillus faecalis and composted biochar in alleviating arsenic toxicity in maize.

Arsenic (As) contamination is a major environmental pollutant that adversely affects plant physiological processes and can hinder nutrients and water availability. Such conditions ultimately resulted in stunted growth, low yield, and poor plant health. Using rhizobacteria and composted biochar (ECB) can effectively overcome this problem. Rhizobacteria have the potential to enhance plant growth by promoting nutrient uptake, producing growth hormones, and suppressing diseases. Composted biochar can enhance plant growth by improving aeration, water retention, and nutrient cycling. Its porous structure supports beneficial microorganisms, increasing nutrient uptake and resilience to stressors, ultimately boosting yields while sequestering carbon. Therefore, the current study was conducted to investigate the combined effect of previously isolated Bacillus faecalis (B. faecalis) and ECB as amendments on maize cultivated under different As levels (0, 300, 600 mg As/kg soil). Four treatments (control, 0.5% composted biochar (0.5ECB), B. faecalis, and 0.5ECB + B. faecalis) were applied in four replications following a completely randomized design. Results showed that the 0.5ECB + B. faecalis treatment led to a significant rise in maize plant height (~ 99%), shoot length (~ 55%), root length (~ 82%), shoot fresh (~ 87%), and shoot dry weight (~ 96%), root fresh (~ 97%), and dry weight (~ 91%) over the control under 600As stress. There was a notable increase in maize chlorophyll a (~ 99%), chlorophyll b (~ 81%), total chlorophyll (~ 94%), and shoot N, P, and K concentration compared to control under As stress, also showing the potential of 0.5ECB + B. faecalis treatment. Consequently, the findings suggest that applying 0.5ECB + B. faecalis is a strategy for alleviating As stress in maize plants.

NRAMP6 and NRAMP1 cooperatively regulate root growth and manganese translocation under manganese deficiency in Arabidopsis.

The essential micronutrient manganese (Mn) in plants regulates multiple biological processes including photosynthesis and oxidative stress. Some Natural Resistance-Associated Macrophage Proteins (NRAMPs) have been reported to play critical roles in Mn uptake and reutilization in low Mn conditions. NRAMP6 was demonstrated to regulate cadmium tolerance and iron utilization in Arabidopsis. Nevertheless, it is unclear whether NRAMP6 plays a role in Mn nutrition. Here, we report that NRAMP6 cooperates with NRAMP1 in Mn utilization. Mutation of NRAMP6 in nramp1 but not in a wild-type background reduces root growth and Mn translocation from the roots to shoots under Mn deficient conditions. Grafting experiments revealed that NRAMP6 expression in both the roots and shoots is required for root growth and Mn translocation under Mn deficiency. We also showed that NRAMP1 could replace NRAMP6 to sustain root growth under Mn deficiency, but not vice versa. Mn deficiency does not affect the transcript level of NRAMP6, but is able to increase and decrease the protein accumulation of NRAMP6 in roots and shoots, respectively. Furthermore, NRAMP6 can be localized to both the plasma membrane and endomembranes including the endoplasmic reticulum, and Mn deficiency enhances the localization of NRAMP6 to the plasma membrane in Arabidopsis plants. NRAMP6 could rescue the defective growth of the yeast mutant Δsmf2, which is deficient in endomembrane Mn transport. Our results reveal the important role of NRAMP6 in Mn nutrition and in the long-distance signaling between the roots and shoots under Mn deficient conditions.

Helicobacter pylori-induced fibroblast-derived Serpin E1 promotes gastric cancer growth and peritoneal dissemination through p38 MAPK/VEGFA-mediated angiogenesis.

BACKGROUND: Fibroblasts, especially cancer-associated fibroblasts (CAFs), represent the predominant stromal cell population in the tumor microenvironment and have an important function in tumorigenesis by interacting with tumor cells. However, their interaction remains elusive in an inflammatory tumor microenvironment induced by Helicobacter pylori (H. pylori). METHODS: The expression of Serpin family E member 1 (Serpin E1) was measured in fibroblasts with or without H. pylori infection, and primary gastric cancer (GC) cells. Serpin E1 knockdown and overexpression fibroblasts were generated using Serpin E1 siRNA or lentivirus carrying Serpin E1. Co-culture models of fibroblasts and GC cells or human umbilical vein endothelial cells (HUVECs) were established with direct contact or the Transwell system. In vitro functional experiments and in vivo tumorigenesis assay were employed to study the malignant behaviors of GC cells interacting with fibroblasts. ELISA was used for quantifying the levels of Serpin E1 and VEGFA in the culture supernatant. The tube formation capacity of HUVECs was assessed using a tube formation assay. Recombinant human Serpin E1 (recSerpin E1), anti-Serpin E1 antibody, and a MAPK pathway inhibitor were utilized to treat HUVECs for elucidating the underlying molecular mechanisms. RESULTS: Serpin E1 was predominantly expressed in gastric CAFs. H. pylori infection significantly enhanced the expression and secretion of Serpin E1 by CAFs. Both fibroblast-derived Serpin E1 and recSerpin E1 enhanced the growth, invasion, and migration of GC cells, along with increased VEGFA expression and tube formation in HUVECs. Furthermore, the co-inoculation of GC cells and fibroblasts overexpressing Serpin E1 triggered the expression of Serpin E1 in cancer cells, which facilitated together xenograft tumor growth and peritoneal dissemination of GC cells in nude mice, with an increased expression of Ki67, Serpin E1, CD31 and/or VEGFA. These processes may be mediated by Serpin E1-induced migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs. CONCLUSION: H. pylori infection induces Serpin E1 expression in fibroblasts, subsequently triggering its expression in GC cells through their interaction. Serpin E1 derived from these cells promotes the migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs, thereby facilitating GC growth and peritoneal metastasis. Targeting Serpin E1 signaling is a potential therapy strategy for H. pylori-induced GC.

Dysfunction of the 4-coumarate:coenzyme A ligase 4CL4 impacts aluminum resistance and lignin accumulation in rice.

The root cell wall is the first and primary target of aluminum (Al) toxicity. Monocots such as rice (Oryza sativa) can accumulate appreciable levels of hydroxycinnamic acids (HCAs) to modify and cross-link hemicellulose and/or lignin of the cell wall. Nevertheless, it is unclear whether this HCA-mediated modification of the cell wall is important for Al accumulation and resistance. We previously isolated and characterized a rice ral1 (resistance to aluminum 1) mutant that shows enhanced Al resistance. In this study, we cloned RAL1 and found that it encodes the 4-coumarate:coenzyme A ligase 4CL4, an enzyme putatively involved in lignin biosynthesis. Mutation of RAL1/4CL4 reduces lignin content and increases the accumulation of its substrates 4-coumaric acid (PA) and ferulic acid (FA). We demonstrate that altered lignin accumulation is not required for the enhanced Al resistance in ral1/4cl4 mutants. We found that the increased accumulation of PA and FA can reduce Al binding to hemicellulose and consequently enhance Al resistance in ral1/4cl4 mutants. Al stress is able to trigger PA and FA accumulation, which is likely caused by the repression of the expression of RAL1/4CL4 and its homologous genes. Our results thus reveal that Al-induced PA and FA accumulation is actively and positively involved in Al resistance in rice through the modification of the cell wall and thereby the reduced Al binding to the cell wall.

Transgenic analysis reveals LeACS-1 as a positive regulator of ethylene-induced shikonin biosynthesis in Lithospermum erythrorhizon hairy roots.

The phytohormone ethylene (ET) is a crucial signaling molecule that induces the biosynthesis of shikonin and its derivatives in Lithospermum erythrorhizon shoot cultures. However, the molecular mechanism and the positive regulators involved in this physiological process are largely unknown. In this study, the function of LeACS-1, a key gene encoding the 1-aminocyclopropane-1-carboxylic acid synthase for ET biosynthesis in L. erythrorhizon hairy roots, was characterized by using overexpression and RNA interference (RNAi) strategies. The results showed that overexpression of LeACS-1 significantly increased endogenous ET concentration and shikonin production, consistent with the up-regulated genes involved in ET biosynthesis and transduction, as well as the genes related to shikonin biosynthesis. Conversely, RNAi of LeACS-1 effectively decreased endogenous ET concentration and shikonin production and down-regulated the expression level of above genes. Correlation analysis showed a significant positive linear relationship between ET concentration and shikonin production. All these results suggest that LeACS-1 acts as a positive regulator of ethylene-induced shikonin biosynthesis in L. erythrorhizon hairy roots. Our work not only gives new insights into the understanding of the relationship between ET and shikonin biosynthesis, but also provides an efficient genetic engineering target gene for secondary metabolite production in non-model plant L. erythrorhizon.

Transgenic studies reveal the positive role of LeEIL-1 in regulating shikonin biosynthesis in Lithospermum erythrorhizon hairy roots.

BACKGROUND: The phytohormone ethylene (ET) is a key signaling molecule for inducing the biosynthesis of shikonin and its derivatives, which are secondary metabolites in Lithospermum erythrorhizon. Although ETHYLENE INSENSITIVE3 (EIN3)/EIN3-like proteins (EILs) are crucial transcription factors in ET signal transduction pathway, the possible function of EIN3/EIL1 in shikonin biosynthesis remains unknown. In this study, by targeting LeEIL-1 (L. erythrorhizon EIN3-like protein gene 1) at the expression level, we revealed the positive regulatory effect of LeEIL-1 on shikonin formation. RESULTS: The mRNA level of LeEIL-1 was significantly up-regulated and down-regulated in the LeEIL-1-overexpressing hairy root lines and LeEIL-1-RNAi hairy root lines, respectively. Specifically, LeEIL-1 overexpression resulted in increased transcript levels of the downstream gene of ET signal transduction pathway (LeERF-1) and a subset of genes for shikonin formation, excretion and/or transportation (LePAL, LeC4H-2, Le4CL-1, HMGR, LePGT-1, LeDI-2, and LePS-2), which was consistent with the enhanced shikonin contents in the LeEIL-1-overexpressing hairy root lines. Conversely, LeEIL-1-RNAi dramatically repressed the expression of the above genes and significantly reduced shikonin production. CONCLUSIONS: The results revealed that LeEIL-1 is a positive regulator of the biosynthesis of shikonin and its derivatives in L. erythrorhizon hairy roots. Our findings gave new insights into the molecular regulatory mechanism of ET in shikonin biosynthesis. LeEIL-1 could be a crucial target gene for the genetic engineering of shikonin biosynthesis.

Clinicopathological features, prognostic factors, and prognostic survival prediction in patients with extrahepatic bile duct cancer liver metastasis.

PURPOSE: Extrahepatic bile duct cancer (EBDC) is a compound malignant tumor mainly consisting of extrahepatic cholangiocarcinoma and gallbladder carcinoma. Most EBDC patients are diagnosed at an advanced stage characterized by distant metastases, and the liver is one of the common sites of metastasis. Hence, the purpose of this study is to investigate the clinicopathological features, identify prognostic risk factors, and assess the long-term prognosis of extrahepatic bile duct cancer liver metastasis (EBDCLM). METHODS: We identified 1922 eligible EBDCLM patients from the SEER database.Cox regression models were used to predict independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS),and Kaplan-Meier survival curves were drawn. A nomogram was constructed based on the results of multivariate Cox analysis, and the predictive effect of the nomogram was evaluated. RESULTS: Age, surgery, chemotherapy, brain metastasis, and lung metastasis were common independent prognostic factors for OS and CSS, and radiotherapy and bone metastasis were independent prognostic factors for CSS. The Kaplan-Meier survival curves showed a significant increase in survival for patients aged less than or equal to 70 years, undergoing surgery and chemotherapy, and without lung metastases. The results showed that the nomogram constructed by us had good predictability and ha d strong clinical application value. CONCLUSION: Our study identified age, surgery, chemotherapy, brain metastasis, and lung metastasis as independent prognostic factors for EBDCLM patients. The nomogram can accurately predict the survival probability, which is helpful for clinicians to assess the prognosis of patients with advanced EBDC and provide personalized clinical decisions.

Effects of simulated acid rain on hydrochemical factors and microbial community structure in red soil aquifers.

Acid rain can lower the pH of groundwater and affect its hydrogeochemistry and microbial ecology. However, the effects of acid rain on the hydrogeochemistry and microbial ecology of red soil groundwater systems in southern China are poorly understood. Previous research had mainly investigated the sources and patterns of groundwater acidification, but not the microbial mechanisms that contribute to this process and their associations with hydrochemical factors. To address this knowledge gap, we conducted a soil column experiment to simulate the infiltration of acid rain through various filter materials (coarse, medium, and fine sand) and to examine the hydrochemical and microbial features of the infiltrate, which can reveal how simulated acid rain (pH 3.5-7.0) alters the hydrochemistry and microbial community composition in red soil aquifers. The results showed that the pH of the leachate decreased due to simulated acid rain, and that the leaching efficiency of nitrogen and metal ions was influenced by the particle size of the filter media. Illumina 16S rRNA gene sequencing revealed that the leachate was dominated by Proteobacteria, Patescibacteria, Actinobacteria, and Acidobacteria, with Proteobacteria accounting for 67.04-74.69% of the bacterial community and containing a high proportion of nitrifying and denitrifying bacteria. Additionally, several genera with heavy metal tolerance, such as Burkholderia-Caballeronia-Paraburkholderia, Delftia, Methylversatilis, Aquicella, and Ralstonia, were widely distributed in the leachate, indicating the strong adaptive capacity of the microbial population. A correlation analysis between the hydrochemical factors and the microbial community structure revealed that pH was the most influential factor, followed by NO2--N, Fe, Al, Cu, Mn, and others. These results indicate that acidification modifies the hydrochemical conditions of the aquifer, creating an environment that is unfavorable for microbial growth and survival. However, some microorganisms may acquire resistance genes to cope with environmental changes.

Comprehensive application of modern technologies in precise liver resection.

BACKGROUND: Liver surgery has gone through the phases of wedge liver resection, regular resection of hepatic lobes, irregular and local resection, extracorporeal hepatectomy, hemi-extracorporeal hepatectomy and Da Vinci surgical system-assisted hepatectomy. Taking advantage of modern technologies, liver surgery is stepping into an age of precise liver resection. This review aimed to analyze the comprehensive application of modern technologies in precise liver resection. DATA SOURCE: PubMed search was carried out for English-language articles relevant to precise liver resection, liver anatomy, hepatic blood inflow blockage, parenchyma transection, and down-staging treatment. RESULTS: The 3D image system can imitate the liver operation procedures, conduct risk assessment, help to identify the operation feasibility and confirm the operation scheme. In addition, some techniques including puncture and injection of methylene blue into the target Glisson sheath help to precisely determine the resection. Alternative methods such as Pringle maneuver are helpful for hepatic blood inflow blockage in precise liver resection. Moreover, the use of exquisite equipment for liver parenchyma transection, such as cavitron ultrasonic surgical aspirator, ultrasonic scalpel, Ligasure and Tissue Link is also helpful to reduce hemorrhage in liver resection, or even operate exsanguinous liver resection without blocking hepatic blood flow. Furthermore, various down-staging therapies including transcatheter arterial chemoembolization and radio-frequency ablation were appropriate for unresectable cancer, which reverse the advanced tumor back to early phase by local or systemic treatment so that hepatectomy or liver transplantation is possible. CONCLUSIONS: Modern technologies mentioned in this paper are the key tool for achieving precise liver resection and can effectively lead to maximum preservation of anatomical structural integrity and functions of the remnant liver. In addition, large randomized trials are needed to evaluate the usefulness of these technologies in patients with hepatocellular carcinoma who have undergone precise liver resection.

Mycorrhizae Enhance Soybean Plant Growth and Aluminum Stress Tolerance by Shaping the Microbiome Assembly in an Acidic Soil.

Strongly acidic soils are characterized by high aluminum (Al) toxicity and low phosphorus (P) availability, which suppress legume plant growth and nodule development. Arbuscular mycorrhizal fungi (AMF) stimulate rhizobia and enhance plant P uptake. However, it is unclear how this symbiotic soybean-AMF-rhizobial trio promotes soybean growth in acidic soils. We examined the effects of AMF and rhizobium addition on the growth of two soybean genotypes, namely, Al-tolerant and Al-sensitive soybeans as well as their associated bacterial and fungal communities in an acidic soil. With and without rhizobial addition, AMF significantly increased the fresh shoot and root biomass of Al-tolerant soybean by 47%/87% and 37%/24%, respectively. This increase in plant biomass corresponded to the enrichment of four plant growth-promoting rhizobacteria (PGPR) in the rhizospheric soil, namely, Chitinophagaceae bacterium 4GSH07, Paraburkholderia soli, Sinomonas atrocyanea, and Aquincola tertiaricarbonis. For Al-sensitive soybean, AMF addition increased the fresh shoot and root biomass by 112%/64% and 30%/217%, respectively, with/without rhizobial addition. Interestingly, this significant increase coincided with a decrease in the pathogenic fungus Nigrospora oryzae as well as an increase in S. atrocyanea, A. tertiaricarbonis, and Talaromyces verruculosus (a P-solubilizing fungus) in the rhizospheric soil. Lastly, the compartment niche along the soil-plant continuum shaped microbiome assembly, with pathogenic/saprotrophic microbes accumulating in the rhizospheric soil and PGPR related to nitrogen fixation or stress resistance (e.g., Rhizobium leguminosarum and Sphingomonas azotifigens) accumulating in the endospheric layer. IMPORTANCE Taken together, this study examined the effects of arbuscular mycorrhizal fungi (AMF) and rhizobial combinations on the growth of Al-tolerant and Al-sensitive soybeans as well as their associated microbial communities in acidic soils and concluded that AMF enhances soybean growth and Al stress tolerance by recruiting PGPR and altering the root-associated microbiome assembly in a host-dependent manner. In the future, these findings will help us better understand the impacts of AMF on rhizosphere microbiome assembly and will contribute to the development of soybean breeding techniques for the comprehensive use of PGPR in sustainable agriculture.

Beneficial effects of splenectomy on liver regeneration in a rat model of massive hepatectomy.

BACKGROUND: Small-for-size syndrome is a widely recognized clinical complication after living donor liver transplantation or extended hepatectomy due to inadequate liver mass. The purpose of this study was to investigate the role of splenectomy in rats after massive hepatectomy, a surrogate model of small-for-size graft. METHODS: Rats were divided into eight groups, each with 20 animals: 50% hepatectomy (50% Hx), 50% hepatectomy+splenectomy (50% Hx+Sp), 60% Hx, 60% Hx+Sp, 70% Hx, 70% Hx+Sp, 90% Hx and 90% Hx+Sp. The following parameters were evaluated: liver function tests (ALT, AST and TBIL), liver regeneration ratio, DNA synthesis, proliferation cell nuclear antigen, hepatic oxygen delivery (HDO2) and hepatic oxygen consumption (HVO2). RESULTS: The liver regeneration ratio was enhanced in the Hx+Sp groups (P<0.05). In addition, compared with the Hx groups, the Hx+Sp groups had better liver functions (P<0.05). DNA synthesis and proliferation cell nuclear antigen were also increased in the Hx+Sp groups compared with the Hx groups (P<0.05). Furthermore, in the Hx+Sp groups, HDO2 and HVO2 were increased over those in the Hx groups (P<0.05), and were positively correlated with the liver regeneration ratio. CONCLUSIONS: Splenectomy significantly improved liver function, and enhanced DNA synthesis and proliferation cell nuclear antigen after massive hepatectomy in rats. This operation could be mediated through increased HDO2 and HVO2, which facilitate liver regeneration.

Kruppel-like factor 9 inhibits growth and metastasis of cholangiocarcinoma cells by targeted regulation of metallothionein 1 M transcription.

This study is to investigate the effect of Kruppel-like factor 9 (KLF9) on the occurrence and progression of cholangiocarcinoma (CCA) and its underlying mechanism. After the CCA cells were transfected with OE-KLF9 and/or sh-metallothionein 1 M (sh-MT1M), KLF9 and MT1M expression levels were measured. Likewise, the biological characteristics of CCA cells were measured, followed by detections of caspase3 activity and epithelial mesenchymal transition (EMT)-related protein. Furthermore, the binding site of KLF9 and MT1M was predicted and verified. An in vivo model of CCA in nude mice was established where tumor volume and weight were recorded, in addition to tumor metastasis in the liver. The expression of KLF9 and MT1M in the CCA cells was remarkably lower. CCA cells overexpressing KLF9 showed repressed abilities to proliferate, invade, and migrate, and strengthened cell apoptosis. KLF9 inhibited EMT, growth, and migration of CCA cells by modulating MT1M transcription. Additionally, KLF9 facilitated MT1M expression in vivo and improve the progression of CCA in nude mice. KLF9 acted as a transcription factor of MT1M to promote its transcription level, thereby affecting the growth and migration of CCA cells, and ultimately improving the occurrence and development of CCA.

Whole-genome sequencing and comparative analysis of Helicobacter pylori GZ7 strain isolated from China.

Helicobacter pylori (H. pylori) is a Gram-negative pathogen as a carcinogen of the class Ι, with unique genetic diversity and wide geographic differences. The high incidence of gastric cancer in East Asia may be related to the bacterial genotype. It is of great significance that the genome of H. pylori in East Asia is widely collected. Therefore, we combined two sequencing technologies (PacBio and Illumina HiSeq 4000) and multiple databases to sequence and annotate the whole genome of H. pylori GZ7 isolated from a gastric cancer patient in Guizhou, China. Furthermore, this sequence was further compared with the genome sequence of 23 H. pylori strains isolated from different regions through collinearity comparison, specific gene analysis, phylogenetic tree construction, etc. The results showed that the genome of H. pylori GZ7 consists of 1,579,995 bp circle chromosomes with a GC content of 39.51%. This chromosome has 1,572 coding sequences, three antibiotic resistance genes, five prophages, and 198 virulence genes. The comparative genome analyses showed that H. pylori GZ7 has 53 specific genes compared to the other 23 strains. Most of these specific genes have not been annotated and characterized until now, whose research may provide insights into the biological activities of this strain. H. pylori GZ7 has the closest genetic relationship with H. pylori F30, and the farthest genetic relationship with H. pylori ELS37, which indicates that H. pylori genomes have geographical differences. This information may provide a molecular basis and guidance for constructing diagnostic methods for H. pylori and researching subsequent experiments.

Excess copper promotes catabolic activity of gram-positive bacteria and resistance of gram-negative bacteria but inhibits fungal community in soil.

The extensive use of copper fungicides has resulted in significant non-target effects on soil microbial communities. However, the documented effects are often variable and contradictory, depending on the methods used to assess them. In this study, we examined the effects of copper accumulation in surface soils on microbial catabolic activity, active biomass and composition, and sensitive bacterial species. The community-level catabolic profiles (CLCPs) showed that both normal (50 mg CuSO4 kg-1 soil) and high dosages (tenfold rate) of CuSO4 significantly increased the catabolic diversity of gram-positive bacteria, while the high dosage increased the overall catabolic activity of gram-negative bacteria. The phospholipid fatty acid (PLFA) analysis showed that the high dosage reduced the biomass of gram-positive bacteria by 27% but did not affect that of gram-negative bacteria. In comparison, the normal and high dosages decreased the fungal biomass by 34% and 58%, respectively. Furthermore, 16S rRNA-denaturing gradient gel electrophoresis (DGGE) fingerprint revealed that more than two-thirds of identified bands belonged to gram-negative bacteria. Some Cu-resistant gram-negative bacterial genera, such as Actinobacterium, Pseudomonas, and Proteobacterium, were detected in the soil to which the high dosage of CuSO4 had been applied. In conclusion, an excess application of CuSO4 increased the catabolic diversity of gram-positive bacteria and induced resistance in gram-negative bacteria, whereas the active fungal community displayed a dosage-dependent response to CuSO4 and can thus be used as a sensitive indicator of copper contamination.

Altered expression levels of miRNAs in serum as sensitive biomarkers for early diagnosis of traumatic injury.

MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides in length which regulate gene expression negatively and play important roles in many pathological processes. It has been demonstrated that circulating miRNAs hold promise to serve as practicable molecular markers for diverse physiological and pathological conditions. In this investigation, we chose partial hepatectomy (PH) as traumatic injury model. There were significantly differential expression of miRNAs in rat serum post-traumatic injury (21 miRNAs were more than twofold up-regulated). Especially, the expression of miR-9 showed the highest up-regulated (>70-fold), and it possessed the characteristics of biomarker that was more sensitive than aspartate aminotransferase and alanine aminotransferase and C-reactive protein for traumatic liver injury. There was also a prominent increase in the expression levels of miR-9 in different brain areas after traumatic injury. Our data suggest that serum miR-9 may serve as promising biomarker for traumatic injury with high sensitivity. Furthermore, these findings may help to elucidate the complex network which mediates stress response to traumatic injury.

Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat.

BACKGROUND: Mechanisms underlying pain in chronic pancreatitis (CP) are incompletely understood. Our previous data showed that astrocytes were actively involved. However, it was unclear how astrocytic activation was induced in CP conditions. In the present study, we hypothesized that toll-like receptors (TLRs) were involved in astrocytic activation and pain behavior in CP-induced pain. RESULTS: To test our hypothesis, we first investigated the changes of TLR2-4 in the rat CP model induced by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). Western blot showed that after TNBS infusion, TLR3, but not TLR2 or TLR4, was increased gradually and maintained at a very high level for up to 5 w, which correlated with the changing course of mechanical allodynia. Double immunostaining suggested that TLR3 was highly expressed on astrocytes. Infusion with TLR3 antisense oligodeoxynucleotide (ASO) dose-dependently attenuated CP-induced allodynia. CP-induced astrocytic activation in the spinal cord was also significantly suppressed by TLR3 ASO. Furthermore, real-time PCR showed that IL-1ß, TNF-α, IL-6 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in spinal cord of pancreatic rats. In addition, TLR3 ASO significantly attenuated CP-induced up-regulation of IL-1ß and MCP-1. CONCLUSIONS: These results suggest a probable "TLR3-astrocytes-IL-1ß/MCP-1" pathway as a positive feedback loop in the spinal dorsal horn in CP conditions. TLR3-mediated neuroimmune interactions could be new targets for treating persistent pain in CP patients.

Deciphering the rhizobacterial assemblages under the influence of genetically engineered maize carrying mcry genes.

Genetically engineered (GE) maize has been thoroughly studied regarding its agro-environmental impact; however, its concerns for the soil environment remain. This work was aimed to decode rhizosphere microbe interactions and potential ecological hazards associated with GE maize. Rhizobacterial communities of field grown transgenic insect-resistant 2A5 maize carrying mcry1Ab and mcry2Ab genes were compared with control Z58 using PacBio sequencing platform. Also full-length 16S rDNA gene sequencing was used to verify the partial (V3-V4) sequencing results obtained in 2017. Measures of α-diversity displayed transgenic 2A5 to be significantly lower in species richness at the flowering stage; however, diversity remained undisturbed. ß-diversity was least affected by genetic modifications where similar community profiles were shared by transgenic 2A5 and control Z58. In addition, root exudation patterns were found to drive variations in bacterial assemblages based on developmental stages. For example, genus Massilia successfully colonized the rhizosphere at jointing stage, while Mucilaginobacter showed higher relative abundance in flowering stages of both 2A5 and Z58. These members are known to possess attributes related to plant growth. The impact of dual-transgene insertion on nifH gene abundance was also analyzed where no apparent significant difference in nifH gene copy number was observed. Our results confirmed that full-length 16S rDNA sequencing was sufficient to provide higher taxonomic resolution. Also, results of our 2-year field trials confirmed that there is no significant impact of mcry gene integration on belowground biomasses. Therefore, GE insect-resistant 2A5 maize carrying mcry1Ab and mcry2Ab genes can continue to benefit human populations by increasing crop productivity. In future, further research needs to be catalyzed to analyze the impact of Bt-insertion on microbial community structure across the years for ecosystem sustainability.

Real-world use of nonvitamin K antagonist oral anticoagulant in atrial fibrillation patients with liver disease: A meta-analysis.

Several studies have investigated the effectiveness and safety of nonvitamin K antagonist oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and liver disease. Herein, we conducted a meta-analysis to compare the effect of NOACs with VKAs in patients with AF and liver disease. We also conducted a subsidiary analysis to compare the risk of liver injury between NOACs and VKA in AF patients. We systematically searched the PubMed and Embase databases from January 2009 to May 2020 for the relevant studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were selected and pooled using a random-effects model. A total of six cohorts were included. Compared with VKA use, the use of NOACs was associated with reduced risks of stroke or systemic embolism (HR 0.68, 95% CI 0.49-0.93), all-cause death (HR 0.69, 95% CI 0.63-0.75), and intracranial bleeding (HR 0.49, 95% CI 0.40-0.59), whereas the outcomes of major bleeding (HR 0.72, 95% CI 0.51-1.01) and gastrointestinal bleeding (HR 0.84, 95% CI 0.51-1.36) were not significantly different between groups in AF patients with liver disease. Moreover, compared with VKA use, the use of NOACs was associated with a reduced risk of liver injury (HR 0.72, 95% CI 0.61-0.84) in AF patients. Compared with VKAs, the use of NOACs was associated with reduced risks of stroke or systemic embolism, all-cause death, and intracranial bleeding in AF patients with liver disease, and associated with a reduced risk of liver injury in AF patients.

A novel epigenetic signature to predict recurrence-free survival in patients with colon cancer.

BACKGROUND: DNA methylation plays an important role in the initiation and progression of colon cancer. The aim of the present study was to perform a comprehensive analysis of DNA methylation and gene expression profiles in order to develop a signature to predict recurrence-free survival (RFS) of colon cancer. METHODS: DNA methylation and mRNA expression data were obtained from TCGA database, and were analyzed using an R package MethylMix. Functional enrichment analysis was performed on statistically significant genes identified by MethylMix criteria. The epigenetic signature and nomogram associated with the RFS of colon cancer were established by the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. Additionally, a joint survival analysis of gene expression and methylation was performed to identify potential prognostic factors for patients with colon cancer. RESULTS: A total of 179 differentially methylated genes were obtained using MethylMix algorithm. An epigenetic signature for RFS was developed using LASSO. Patients with high-risk had significantly worse RFS than those with low-risk. The signature is independent of clinicopathological variables and indicated better predictive power than other clinicopathological variables in patients with colon cancer. Moreover, joint survival analysis of gene expression and methylation revealed that seven methylated genes could be independent prognostic factors for RFS in colon cancer. CONCLUSIONS: Our proposed epigenetic signature presents potential prognostic significance in assessing recurrence risk stratification for patients with colon cancer.

Differential Impacts on Bacterial Composition and Abundance in Rhizosphere Compartments between Al-Tolerant and Al-Sensitive Soybean Genotypes in Acidic Soil.

In this study, two soybean genotypes i.e. aluminum-tolerant Baxi 10 (BX10) and aluminum-sensitive Bendi 2 (BD2) were used as plant materials and the acidic red soil was used as growth medium. The soil layers from the inside to the outside of the root are: rhizospheric soil after washing (WRH), rhizospheric soil after brushing (BRH) and rhizospheric soil at two sides (SRH), respectively. The rhizosphere bacterial communities were analyzed by high-throughput sequencing of V4 hypervariable regions of 16S rRNA gene (16S rDNA) amplicons via Illumina MiSeq. The results of alpha diversity showed that the BRH and SRH of BX10 were significantly lower on community richness than that of BD2, while the WRH existed no significant difference between BX10 and BD2. Among the three sampling compartments of the same soybean genotype, WRH had the lowest community richness and diversity while existed the highest coverage. Beta diversity analysis results displayed no significant difference for any compartment between the two genotypes, or among the three different sampling compartments for any same soybean genotype. However, the relative abundance of major bacterial taxa specifically nitrogen-fixating and/or aluminum-tolerant bacteria was significantly different in the compartments of the BRH and/or SRH at phylum and genus levels depicting genotype dependent variations in rhizosphere bacterial community. Strikingly, as compared with BRH and SRH, the WRH within the same genotype (BX10 or BD2) always had an enrichment effect on rhizosphere bacteria associated with nitrogen-fixation.