Bacillus suppresses nitrogen efficiency of soybean-rhizobium symbiosis through regulation of nitrogen-related transcriptional and microbial patterns.

The regulation of legume-rhizobia symbiosis by microorganisms has obtained considerable interest in recent research, particularly in the common rhizobacteria Bacillus. However, few studies have provided detailed explanations regarding the regulatory mechanisms involved. Here, we investigated the effects of Bacillus (Bac.B) on Bradyrhizobium-soybean (Glycine max) symbiosis and elucidated the underlying ecological mechanisms. We found that two Bradyrhizobium strains (i.e. Bra.Q2 and Bra.D) isolated from nodules significantly promoted nitrogen (N) efficiency of soybean via facilitating nodule formation, thereby enhanced plant growth and yield. However, the intrusion of Bac.B caused a reverse shift in the synergistic efficiency of N2 fixation in the soybean-Bradyrhizobium symbiosis. Biofilm formation and naringenin may be importantin suppression of Bra.Q2 growth regulated by Bac.B. In addition, transcriptome and microbiome analyses revealed that Bra.Q2 and Bac.B might interact to regulateN transport and assimilation, thus influence the bacterial composition related to plant N nutrition in nodules. Also, the metabolisms of secondary metabolites and hormones associated with plant-microbe interaction and growth regulation were modulated by Bra.Q2 and Bac.B coinoculation. Collectively, we demonstrate that Bacillus negatively affects Bradyrhizobium-soybean symbiosis and modulate microbial interactions in the nodule. Our findings highlight a novel Bacillus-based regulation to improve N efficiency and sustainable agricultural development.

AcEXPA1, an α-expansin gene, participates in the aluminum tolerance of carpetgrass (Axonopus compressus) through root growth regulation.

KEY MESSAGE: AcEXPA1, an aluminum (Al)-inducible expansin gene, is demonstrated to be involved in carpetgrass (Axonopus compressus) root elongation under Al toxicity through analyzing composite carpetgrass plants overexpressing AcEXPA1. Aluminum (Al) toxicity is a major mineral toxicity that limits plant productivity in acidic soils by inhibiting root growth. Carpetgrass (Axonopus compressus), a dominant warm-season turfgrass widely grown in acidic tropical soils, exhibits superior adaptability to Al toxicity. However, the mechanisms underlying its Al tolerance are largely unclear, and knowledge of the functional genes involved in Al detoxification in this turfgrass is limited. In this study, phenotypic variation in Al tolerance, as indicated by relative root elongation, was observed among seventeen carpetgrass genotypes. Al-responsive genes related to cell wall modification were identified in the roots of the Al-tolerant genotype 'A58' via transcriptome analysis. Among them, a gene encoding α-expansin was cloned and designated AcEXPA1 for functional characterization. Observed Al dose effects and temporal responses revealed that Al induced AcEXPA1 expression in carpetgrass roots. Subsequently, an efficient and convenient Agrobacterium rhizogenes-mediated transformation method was established to generate composite carpetgrass plants with transgenic hairy roots for investigating AcEXPA1 involvement in carpetgrass root growth under Al toxicity. AcEXPA1 was successfully overexpressed in the transgenic hairy roots, and AcEXPA1 overexpression enhanced Al tolerance in composite carpetgrass plants through a decrease in Al-induced root growth inhibition. Taken together, these findings suggest that AcEXPA1 contributes to Al tolerance in carpetgrass via root growth regulation.

The Silkworm Carboxypeptidase Inhibitor Prevents Gastric Cancer Cells' Proliferation through the EGF/EGFR Signaling Pathway.

Gastric cancer is a common malignant tumor originating from the gastric mucosa epithelium. Studies have shown that bioactive substances such as antimicrobial peptides and cantharidin contained in a variety of insects can exert anti-cancer functions; when compared with chemotherapy drugs, these bioactive substances have less toxicity and reduced side effects. Here, we report the first Bombyx mori carboxypeptidase inhibitor that is specifically and highly expressed in silk glands, which can significantly prevent the proliferation of gastric cancer cells by inhibiting the MAPK/ERK pathway initiated by EGF/EGFR through the promotion of expression of the proto-oncogene c-Myc, thereby affecting the expression of related cyclins. Through molecular docking and virtual screening of silkworm carboxypeptidase inhibitors and epidermal growth factor receptors, we identified a polypeptide that overlapped with existing small-molecule inhibitors of the receptor. In the present work, we explore the medicinal potential and application of silkworm carboxypeptidase inhibitors to promote the development of anti-tumor drugs from insect-derived substances.

Physiological and transcriptomic analyses reveal the roles of secondary metabolism in the adaptive responses of Stylosanthes to manganese toxicity.

BACKGROUND: As a heavy metal, manganese (Mn) can be toxic to plants. Stylo (Stylosanthes) is an important tropical legume that exhibits tolerance to high levels of Mn. However, little is known about the adaptive responses of stylo to Mn toxicity. Thus, this study integrated both physiological and transcriptomic analyses of stylo subjected to Mn toxicity. RESULTS: Results showed that excess Mn treatments increased malondialdehyde (MDA) levels in leaves of stylo, resulting in the reduction of leaf chlorophyll concentrations and plant dry weight. In contrast, the activities of enzymes, such as peroxidase (POD), phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO), were significantly increased in stylo leaves upon treatment with increasing Mn levels, particularly Mn levels greater than 400 µM. Transcriptome analysis revealed 2471 up-regulated and 1623 down-regulated genes in stylo leaves subjected to Mn toxicity. Among them, a set of excess Mn up-regulated genes, such as genes encoding PAL, cinnamyl-alcohol dehydrogenases (CADs), chalcone isomerase (CHI), chalcone synthase (CHS) and flavonol synthase (FLS), were enriched in secondary metabolic processes based on gene ontology (GO) analysis. Numerous genes associated with transcription factors (TFs), such as genes belonging to the C2H2 zinc finger transcription factor, WRKY and MYB families, were also regulated by Mn in stylo leaves. Furthermore, the C2H2 and MYB transcription factors were predicted to be involved in the transcriptional regulation of genes that participate in secondary metabolism in stylo during Mn exposure. Interestingly, the activation of secondary metabolism-related genes probably resulted in increased levels of secondary metabolites, including total phenols, flavonoids, tannins and anthocyanidins. CONCLUSIONS: Taken together, this study reveals the roles of secondary metabolism in the adaptive responses of stylo to Mn toxicity, which is probably regulated by specific transcription factors.

Physiological responses and proteomic changes reveal insights into Stylosanthes response to manganese toxicity.

BACKGROUND: Manganese (Mn), an essential element for plants, can be toxic when present in excess. Stylo (Stylosanthes) is a pioneer tropical legume with great potential for Mn tolerance, but its Mn tolerance mechanisms remain poorly understood. RESULTS: In this study, variations in Mn tolerance were observed among nine stylo genotypes. Stylo genotype 'RY5' exhibited the highest Mn tolerance compared to the other tested genotypes, whereas 'TF2001' was a Mn-sensitive genotype. The mechanisms underlying the response of stylo to Mn toxicity were further investigated using these two genotypes with contrasting Mn tolerance. Results showed that stylo genotype RY5 exhibited Mn tolerance superior to that of genotype TF2001, showing lower reductions in leaf chlorophyll concentration, chlorophyll fluorescence parameters, photosynthetic indexes and plant dry weight under Mn toxicity. A label-free quantitative proteomic analysis was conducted to investigate the protein profiles in the leaves and roots of RY5 in response to Mn toxicity. A total of 356 differentially expressed proteins (DEPs) were identified, including 206 proteins from leaves and 150 proteins from roots, which consisted of 71 upregulated, 62 downregulated, 127 strongly induced and 96 completely suppressed proteins. These DEPs were mainly involved in defense response, photosynthesis, carbon fixation, metabolism, cell wall modulation and signaling. The qRT-PCR analysis verified that 10 out of 12 corresponding gene transcription patterns correlated with their encoding proteins after Mn exposure. Finally, a schematic was constructed to reveal insights into the molecular processes in the leaves and roots of stylo in response to Mn toxicity. CONCLUSIONS: These findings suggest that stylo plants may cope with Mn toxicity by enhancing their defense response and phenylpropanoid pathways, adjusting photosynthesis and metabolic processes, and modulating protein synthesis and turnover. This study provides a platform for the future study of Mn tolerance mechanisms in stylo and may lead to a better understanding of the potential mechanisms underlying tropical legume adaptation to Mn toxicity.

Advances in the Mechanisms of Plant Tolerance to Manganese Toxicity.

Manganese (Mn) is an essential element for plant growth due to its participation in a series of physiological and metabolic processes. Mn is also considered a heavy metal that causes phytotoxicity when present in excess, disrupting photosynthesis and enzyme activity in plants. Thus, Mn toxicity is a major constraint limiting plant growth and production, especially in acid soils. To cope with Mn toxicity, plants have evolved a wide range of adaptive strategies to improve their growth under this stress. Mn tolerance mechanisms include activation of the antioxidant system, regulation of Mn uptake and homeostasis, and compartmentalization of Mn into subcellular compartments (e.g., vacuoles, endoplasmic reticulum, Golgi apparatus, and cell walls). In this regard, numerous genes are involved in specific pathways controlling Mn detoxification. Here, we summarize the recent advances in the mechanisms of Mn toxicity tolerance in plants and highlight the roles of genes responsible for Mn uptake, translocation, and distribution, contributing to Mn detoxification. We hope this review will provide a comprehensive understanding of the adaptive strategies of plants to Mn toxicity through gene regulation, which will aid in breeding crop varieties with Mn tolerance via genetic improvement approaches, enhancing the yield and quality of crops.

Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations.

As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer's disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC50 values < 10 µM on human BChE, selectivity index BChE > 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD.

Genome-Wide Identification and Characterization of Carboxypeptidase Genes in Silkworm (Bombyx mori).

The silkworm (Bombyx mori) is an economically-important insect that can secrete silk. Carboxypeptidases have been found in various metazoan species and play important roles in physiological and biochemical reactions. Here, we analyzed the silkworm genome database and characterized 48 carboxypeptidases, including 34 metal carboxypeptidases (BmMCP1-BmMCP34) and 14 serine carboxypeptidases (BmSCP1-BmSCP14), to better understand their diverse functions. Compared to other insects, our results indicated that carboxypeptidases from silkworm have more family members. These silkworm carboxypeptidases could be divided into four families: Peptidase_M2 carboxypeptidases, Peptidase_M14 carboxypeptidases, Peptidase_S10 carboxypeptidases and Peptidase_S28 carboxypeptidases. Microarray analysis showed that the carboxypeptidases had distinct expression patterns, whereas quantitative real-time PCR demonstrated that the expression level of 13 carboxypeptidases significantly decreased after starvation and restored after re-feeding. Overall, our study provides new insights into the functional and evolutionary features of silkworm carboxypeptidases.

Risk factors for long-term outcome of drug-eluting stenting in adults with early-onset coronary artery disease.

OBJECTIVE: We lack data on the long-term outcome of drug-eluting stenting in patients with early-onset coronary artery disease (CAD). Here, we investigated the association of traditional risk factors and major adverse cardiovascular events (MACEs) after drug-eluting stenting in patients with CAD who were < 50 years old. METHODS: We enrolled 437 consecutive CAD patients < 50 years old who underwent drug-eluting stenting and 132 subjects who were age- and sex-matched and angiographically shown to be disease free as controls. MACEs were analyzed in CAD patients for a median of 24 months [interquartile range 14-34 months]. RESULTS: Male patients accounted for 90.4% of cases. As compared with controls, patients with early-onset CAD had higher body mass index and rates of smoking, family history of CAD, and diabetes and hypercholesterolemia. During the hospital stay, 1 patient died, and the incidence of MACEs was 1.1%. At the end of follow-up, the overall death rate was 0.7%. MACEs were observed in 54 patients (12.4%). On Cox proportional hazard analyses, positive family history and diabetes were independent risk factors of MACEs (HR 2.61, 95% confidence interval 1.29-4.00, p = 0.002; and HR 2.48, 95% confidence interval 0.86-3.14, p = 0.004, respectively). CONCLUSIONS: Drug-eluting stenting is a reliable treatment for patients with early-onset CAD. Positive family history of CAD and diabetes are independent risk factors of adverse cardiovascular events in this subgroup of patients after drug-eluting stent implantation.

Comparison of the efficacy of HoLEP and TURP in the treatment of elderly benign prostatic hyperplasia patients: a retrospective study.

OBJECTIVE: To prove that holmium laser prostatectomy (HoLEP) is safe and effective in the treatment of benign prostatic hyperplasia (BPH), and is superior to transurethral prostatectomy (TURP) for elderly patients. METHODS: We retrospectively studied 565 HoLEP patients and 76 TURP elderly patients. HoLEP patients were first divided into three groups according to their age(Under 65 years old group, 65-79 years old group and over 80 years old group), and their preoperative, intraoperative, and postoperative characteristics were then compared. Secondly, the same characteristics of HoLEP and TURP patients over 80 years were compared. Chi-square test, one-way ANOVA and Fisher's exact test were used in this study. RESULTS: Firstly, we compared HoLEP patients in different age groups and found that there was statistically significant difference in diabetes, CCVD and bladder stones, among the three groups (P<0.05).Secondlye, we compared HoLEP and TURP treatments in elderly patients (≥80 years old). The patients with HoLEP had a higher share of diabetes, CCVD and anticoagulation (P<0.05). Moreover, compared with TURP patients, HoLEP patients had shorter enucleation duration, more enucleate prostate weight, fewer hemoglobin diminutions, shorter bladder irrigation time, shorter catheter-indwelling period, and shorter hospital period (P<0.05). Although there was no difference in IPSS, Qmax and QOL between the two groups before operation (P>0.05), the difference was statistically significant, 6 months after the operation (P<0.05). CONCLUSION: HoLEP is safe and effective for BPH patients, and is superior to transurethral TURP for elderly patients.

The prevalence of hyperuricemia and its correlates in an inland Chinese adult population, urban and rural of Jinan.

Economy has developed rapidly in China, and the clustering of cardiovascular risk factors in subjects increased remarkably over the past two decades. However, no data are available regarding the temporal prevalence of hyperuricemia and its correlates in this rapidly developing area, especially in the inland area. The cross-sectional survey was based on a random sample of 4,218 residents aged 35-64 years in the Jinan area. Hyperuricemia was defined as serum uric acid ≥ 416 µmol/L in men and ≥ 357 µmol/L in women. Subjects underwent physical examination and fasting blood testing. Complete data were available for analysis from 1,979 men and 2,062 women. The age-adjusted prevalence of hyperuricemia was 6.4 % for men and 2.1 % for women. The prevalence of hyperuricemia was greater in urban (6.7 %) than in rural areas (1.7 %) of Jinan city. Multivariate logistic regression models revealed hyperuricemia associated with hypertriglyceridemia [men: odds ratio (OR) = 6.101, 95 % confidence interval (CI) 4.064-9.159; women: OR = 7.103, 95 % CI 3.578-14.099] and high serum creatinine level (men: OR = 2.603, 95 % CI 1.602-4.230; women: OR = 5.237, 95 % CI 2.667-10.284). Hyperuricemia was also significantly associated with male sex, urban residence, hypertension, obesity, and hypercholesterolemia. Age (1-year increase) was negatively associated with hyperuricemia in men but positively associated with hyperuricemia in women. In conclusion, the prevalence of hyperuricemia is higher in urban than rural areas of Jinan, China. Male sex, urban residence, hypertension, obesity, hypercholesterolemia, hypertriglyceridemia, and high serum creatinine level contributed to hyperuricemia in this population.

Independent roles of monocyte chemoattractant protein-1, regulated on activation, normal T-cell expressed and secreted and fractalkine in the vulnerability of coronary atherosclerotic plaques.

BACKGROUND: Monocyte chemotactic factors contribute to the formation of atherosclerotic plaques. The present study aimed to elucidate the roles of monocyte chemoattractant protein-1 (MCP-1), Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and fractalkine on the vulnerability of atherosclerotic plaques in patients with acute myocardial infarction (AMI) or unstable angina pectoris (UAP). METHODS AND RESULTS: Sixty patients with AMI, 60 patients with UAP, 60 patients with stable angina pectoris (SAP) and 40 patients without coronary heart disease comprised the study group. Quantitative coronary angiography and intravascular ultrasound (IVUS) were performed. Concentrations and mRNA expression levels of high-sensitivity C-reactive protein, MCP-1, RANTES and fractalkine were measured by ELISA and RT-PCR, respectively. IVUS found that 51.3% of the AMI patients and 47.7% of the UAP patients had soft lipid plaques. Among the SAP patients, 52.4% had fibrous plaques and only 17.1% had soft plaques. AMI and UAP patients had larger plaque burden and vascular remodeling index than did the SAP patients (P<0.01). The averaged number of migrated monocytes was higher in AMI and UAP patients. Concentrations and mRNA expression levels of MCP-1, RANTES and fractalkine were significantly higher in AMI and UAP patients than in SAP patients (P<0.05-0.01). The plaque burden in UAP patients as measured with IVUS correlated well with monocytes chemotaxis (r=0.56, P<0.01). CONCLUSIONS: MCP-1, RANTES and fractalkine independently participate in the pathogenesis of plaque vulnerability and subsequent plaque rupture.

A Berberine Bridge Enzyme-Like Protein, GmBBE-like43, Confers Soybean's Coordinated Adaptation to Aluminum Toxicity and Phosphorus Deficiency.

Phosphorus (P) deficiency and aluminum (Al) toxicity often coexist and are two major limiting factors for crop production in acid soils. The purpose of this study was to characterize the function of GmBBE-like43, a berberine bridge enzyme-like protein-encoding gene, in soybean (Glycine max) adaptation to Al and low P stresses. Present quantitative real-time PCR (qRT-PCR) assays confirmed the phosphate (Pi)-starvation enhanced and Al-stress up-regulated expression pattern of GmBBE-like43 in soybean roots. Meanwhile, the expression of a GmBBE-like43-GFP chimera in both common bean hairy roots and tobacco leaves demonstrated its cell wall localization. Moreover, both transgenic Arabidopsis and soybean hairy roots revealed the function of GmBBE-like43 in promoting root growth under both Al and low P stresses. GmBBE-like43-overexpression also resulted in more H2O2 production on transgenic soybean hairy root surface with oligogalacturonides (OGs) application and antagonized the effects of Al on the expression of two SAUR-like genes. Taken together, our results suggest that GmBBE-like43 might be involved in the soybean's coordinated adaptation to Al toxicity and Pi starvation through modulation of OGs-oxidation in the cell wall.

Rationale and design for comparison of non-compliant balloon with drug-coating balloon angioplasty for side branch after provisional stenting for patients with true coronary bifurcation lesions: a prospective, multicentre and randomised DCB-BIF trial.

INTRODUCTION: Provisional stenting using drug-eluting stent is effective for simple coronary bifurcation lesions. Kissing balloon inflation using conventional non-compliant balloon is the primary treatment of side branch (SB) after main vessel (MV) stenting. Drug-coating balloon (DCB) is reported to be associated with less frequent clinical events in in-stent restenosis and small vessel disease. The importance of DCB in bifurcation treatment is understudied. Accordingly, this trial is designed to investigate the superiority of DCB to non-compliant balloon angioplasty for SB after provisional stenting in patients with true coronary bifurcation lesions. METHODS AND ANALYSIS: The DCB-BIF trial is a prospective, multicentre, randomised, superiority trial including 784 patients with true coronary bifurcation lesions. Patients will be randomised in a 1:1 fashion to receive either DCB or non-compliant balloon angioplasty if SB diameter stenosis >70% after MV stenting. The primary endpoint is the composite of major adverse cardiac event at the 1-year follow-up, including cardiac death, myocardial infarction (MI) or clinically driven target lesion revascularisation. The major secondary endpoints include all-cause death, periprocedural MI, spontaneous MI, clinically driven target vessel revascularisation, in-stent restenosis, stroke and individual component of the primary endpoint. The safety endpoint is the risk of stent thrombosis. ETHICS AND DISSEMINATION: The study protocol and informed consent have been reviewed and approved by the Institutional Review Board of all participating centres. The written informed consent for participation in the trial will be obtained from all participants. The results of this study will be published in a peer-reviewed journal and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT04242134.

Combination of raloxifene, aspirin and estrogen as novel paradigm of hormone replacement therapy in rabbit model of menopause.

AIM: To assess a novel hormone replacement therapy (HRT) paradigm using raloxifene, aspirin combined with estrogen in rabbit model of menopause. METHODS: Female New Zealand white rabbits were ovariectomized or sham-operated. The ovariectomized rabbits were divided into 7 groups: estradiol valerate (E(2)), raloxifene, aspirin, E(2) /raloxifene, E(2)/aspirin, E(2) /raloxifene/aspirin and vehicle. Two weeks after the operation, the rabbits were administered the above drugs for 12 weeks. Then, the mammary glands were examined histologically, uterus was weighted, and blood sample was collected for analyzing the levels of estrogen, serum lipids and monocyte chemoattractant protein (MCP)-1, and platelet aggregation. The aortic tissue was examined morphometrically. RESULTS: Compared with E(2) 0.1 mg·kg(-1)·d(-1) treatment alone, the pairing of raloxifene 10 mg·kg(-1)·d(-1) with E(2) significantly decreased the extent of mammary gland branches and ducts (5.53%±1.23% vs 15.4%±2.17%, P<0.01), as well as the uterine weight (2.16±0.35 g vs 4.91±0.75 g, P<0.01). However, E(2)/raloxifene or E(2) alone treatment significantly stimulated platelet aggregation relative to vehicle group. Addition of aspirin 5 mg·kg(-1)·d(-1) reduced platelet aggregation to almost the same level as the vehicle group. E(2) treatment exerted a positive effect on serum lipids and MCP-1, and a regression in aortic intimal plaque size compared to the vehicle. Raloxifene reinforced the positive effects of E(2). CONCLUSION: The combination of raloxifene, aspirin and E(2) exhibits positive lipid, MCP-1 and atherosclerotic responses with minimal stimulation of breast and uterine tissues as well as platelet aggregation in a rabbit model of the menopause.

[Roles of monocyte chemoattractant protein-1, RANTES and Fractalkine on promoting vulnerability of atherosclerotic plaques].

OBJECTIVE: To elucidate the roles of monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) on the vulnerability of atherosclerotic plaques in patients with stable (SAP) and unstable angina pectoris (UAP). METHODS: Patients with SAP (n = 50) and UAP (n = 50) underwent coronary angiography (CAG) and intravenous ultrasound (IVUS) were included in the study. Monocyte chemotaxis was assayed by the transwell chamber. Concentrations of hs-CRP, MCP-1, RANTES and Fractalkine were measured by Enzyme-linked-immunosorbent assay (ELISA). mRNA expression of MCP-1, RANTES and Fractalkine in the monocytes was detected by RT-PCR. RESULTS: IVUS evidenced soft lipid plaques in 48% UAP patients and in 16% SAP patients (P < 0.05). SAP patients had mainly fibrous and mixed plaques. Plaque burden and vascular remodeling index were significantly higher in UAP patients than in SAP patients (P < 0.01). The averaged number of migrated monocytes in the UAP patients were higher than that in patients with SAP (P < 0.01). Concentration of hs-CRP, MCP-1, RANTES and Fractalkine were significantly higher in UAP patients than those of SAP patients (P < 0.05 or P < 0.01). mRNA expression of MCP-1, RANTES and Fractalkine in patients with UAP was significantly higher than those of SAP patients (P < 0.05). CONCLUSION: Upregulated monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) might promote coronary plaque vulnerability in UAP patients.

Roles of ncRNAs as ceRNAs in Gastric Cancer.

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC's mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC's ceRNA network.

Characterization of Metal Tolerance Proteins and Functional Analysis of GmMTP8.1 Involved in Manganese Tolerance in Soybean.

Manganese is an essential micronutrient for plant growth but can be toxic to plants when it reaches excessive levels. Although metal tolerance proteins (MTPs), which belong to the cation diffusion facilitator (CDF) family, have been demonstrated to play critical roles in manganese (Mn) tolerance in plants, the characteristics and functions of GmMTP members in the response of soybean (Glycine max) to Mn toxicity have not been documented. In this study, growth inhibition was observed in soybean plants that were exposed to a toxic level of Mn in hydroponics, as reflected by the generation of brown spots, and decreased leaf chlorophyll concentration and plant fresh weight. Subsequent genome-wide analysis resulted in the identification of a total of 14 GmMTP genes in the soybean genome. Among these GmMTPs, 9 and 12 were found to be regulated by excess Mn in leaves and roots, respectively. Furthermore, the function of GmMTP8.1, a Mn-CDF homologue of ShMTP8 identified in the legume Stylosanthes hamata that is involved in Mn detoxification, was characterized. Subcellular localization analysis showed that GmMTP8.1 was localized to the endoplasmic reticulum (ER). Heterologous expression of GmMTP8.1 led to the restoration of growth of the Mn-hypersensitive yeast (Saccharomyces cerevisiae) mutant Δpmr1, which is made defective in Mn transport into the Golgi apparatus by P-type Ca/Mn-ATPase. Furthermore, GmMTP8.1 overexpression conferred tolerance to the toxic level of Mn in Arabidopsis (Arabidopsis thaliana). Under excess Mn conditions, concentrations of Mn in shoots but not roots were decreased in transgenic Arabidopsis, overexpressing GmMTP8.1 compared to the wild type. The overexpression of GmMTP8.1 also led to the upregulation of several transporter genes responsible for Mn efflux and sequestration in Arabidopsis, such as AtMTP8/11. Taken together, these results suggest that GmMTP8.1 is an ER-localized Mn transporter contributing to confer Mn tolerance by stimulating the export of Mn out of leaf cells and increasing the sequestration of Mn into intracellular compartments.

Estimation of SPAD value in waterlogged winter wheat based on characteristic indices of hyperspectral and digital image.

To explore the optimal monitoring method for soil and plant analyzer development (SPAD) of winter wheat under waterlogging stress based on hyperspectral and digital image techno-logy, the correlations between SPAD of the waterlogged winter wheat and fifteen indices of hyperspectral characteristic and fourteen indices of digital image feature were analyzed under a micro-plot which could be irrigated and drainage separately. Then, the BP neural network models for SPAD estimation were constructed based on the optimal monitoring feature indices. Compared with the normal winter wheat, SPAD and the value of hyperspectral reflectance did not change under short-term waterlogging (less than 7 d), whereas the SPAD was significantly decreased after more than 12 d waterlogging treatment with the value being close to zero at the late stage of growth. The estimation accuracy based on the digital image characteristics of green minus red, excess red index, norma-lized redness index and excess green index showed similar results compared to that using the BP network model based on the characteristics of the corresponding hyperspectral band. The highest R2 between the measured value and the predicted value was 0.86, while the root mean square error (RMSE) was 3.98. Compared with the BP network models built with the digital image feathers, the accuracy of the models based on the four hyperspectral characteristic indices (carotenoid reflex index, yellow edge amplitude, normalized difference vegetation index and structure insensitive pigment index) for SPAD was significantly improved, with the highest R2 of 0.97 and the lowest RMSE of 1.95. Our results suggest that both hyperspectral and digital image technology could be used to estimate SPAD value of waterlogged winter wheat and that the BP network model based on hyperspectral characteristic indices performed better in the estimation accuracy.

Novel ß-mannanase/GLP-1 fusion peptide high effectively ameliorates obesity in a mouse model by modifying balance of gut microbiota.

We constructed a novel ß-mannanase/GLP-1 fusion peptide, termed MGLP_1, and evaluated its ability to ameliorate obesity in a high-fat/high-sugar diet (HFSD)-induced mouse model. Eight-wk MGLP_1 treatment notably reduced obesity, as reflected by significant changes of body weight, serum triglyceride level, fatty liver and adipose tissue distribution. Amelioration of HFSD-induced gut dysbiosis by MGLP_1 was evidenced by reduced abundance ratio of bacterial phyla Firmicutes to Bacteroidetes, enhanced abundance of beneficial probiotic genera (Bifidobacterium, Lachnospiraceae, Ileibacterium), and reduced abundance of harmful genera (Clostridium, Romboutsia). Mechanisms of weight loss were investigated by comparing effects of treatment with MGLP_1 vs. prebiotics manno-oligosaccharides (MOS). MGLP_1 ameliorated gut microbiota imbalance by enhancing carbohydrate catabolism, whereas MOS promoted glycan synthesis and metabolism. Our findings, taken together, indicate that MGLP_1 fusion peptide has strong potential for amelioration of obesity by modifying relationships between gut microbiota and lipid and glucose metabolism.