The peptide GOLVEN10 alters root development and noduletaxis in Medicago truncatula.

The conservation of GOLVEN (GLV)/ROOT MERISTEM GROWTH FACTOR (RGF) peptide encoding genes across plant genomes capable of forming roots or root-like structures underscores their potential significance in the terrestrial adaptation of plants. This study investigates the function and role of GOLVEN peptide-coding genes in Medicago truncatula. Five out of fifteen GLV/RGF genes were notably upregulated during nodule organogenesis and were differentially responsive to nitrogen deficiency and auxin treatment. Specifically, the expression of MtGLV9 and MtGLV10 at nodule initiation sites was contingent upon the NODULE INCEPTION transcription factor. Overexpression of these five nodule-induced GLV genes in hairy roots of M. truncatula and application of their synthetic peptide analogues led to a decrease in nodule count by 25-50%. Uniquely, the GOLVEN10 peptide altered the positioning of the first formed lateral root and nodule on the primary root axis, an observation we term 'noduletaxis'; this decreased the length of the lateral organ formation zone on roots. Histological section of roots treated with synthetic GOLVEN10 peptide revealed an increased cell number within the root cortical cell layers without a corresponding increase in cell length, leading to an elongation of the root likely introducing a spatiotemporal delay in organ formation. At the transcription level, the GOLVEN10 peptide suppressed expression of microtubule-related genes and exerted its effects by changing expression of a large subset of Auxin responsive genes. These findings advance our understanding of the molecular mechanisms by which GOLVEN peptides modulate root morphology, nodule ontogeny, and interactions with key transcriptional pathways.

Manure replacing synthetic fertilizer improves crop yield sustainability and reduces carbon footprint under winter wheat-summer maize cropping system.

Manure replacing synthetic fertilizer is a viable practice to ensure crop yield and increase soil organic carbon (SOC), but its impact on greenhouse gas (GHG) emissions is inconsistent, thus remains its effect on CF unclear. In this study, a 7-year field experiment was conducted to assess the impact of replacing synthetic fertilizer with manure on crop productivity, SOC sequestration, GHG emissions and crop CF under winter wheat-summer maize cropping system. Five treatments were involved: synthetic nitrogen, phosphorus, and potassium fertilizer (NPK) and 25%, 50%, 75%, and 100% of manure replacing synthetic N (25%M, 50%M, 75%M, and 100%M). Compared with NPK treatment, 25%M and 50%M treatments maintained annual yield (winter wheat plus summer maize) and sustainable yield index (SYI), but 75%M and 100%M treatments significantly decreased annual yield, and 100%M treatment also significantly reduced annual SYI. The SOC content exhibited a significant increasing trend over years in all treatments. After 7 years, SOC storage in manure treatments increased by 3.06-11.82 Mg ha-1 relative to NPK treatment. Manure treatments reduced annual GHG emissions by 14%-60% over NPK treatment. The CF of the cropping system ranged from 0.16 to 0.39 kg CO2 eq kg-1 of grain without considering SOC sequestration, in which the CF of manure treatments lowered by 18%-58% relative to NPK treatment. When SOC sequestration was involved in, the CF varied from -0.39 to 0.37 kg CO2 eq kg-1 of grain, manure treatments significantly reduced the CF by 22%-208% over NPK treatment. It was concluded that replacing 50% of synthetic fertilizer with manure was a sound option for achieving high crop yield and SYI but low CF under the tested cropping system.

Prevalence and genotype distribution of human papillomavirus infection among female outpatients in Northeast China: a population-based survey of 110,927 women.

PURPOSE: Human papillomavirus (HPV) infection, especially high-risk HPV, is a major etiological factor for cervical cancer. This study aimed to investigate the distribution of human papillomavirus infection among female outpatients in Northeast China. METHODS: A total of 110,927 women aged between 18 and 80 years from Shengjing Hospital of China Medical University, tested with the HPV Geno-Array Test Kit (HybriBio), were enrolled in this study. RESULTS: The overall prevalence of HPV infection in the study population was 16.95% (18,802/110,927). A total of 21 HPV genotypes were identified and the six most prevalent ones were HPV16 (5.78%), HPV58 (2.62%), HPV52 (1.91%), HPV33 (1.55%), HPV53 (1.45%), and HPV18 (1.16%). The prevalence of single HPV was 83.58% (15,714/18802) and that of multiple HPV was 16.42% (3088/18802). HPV16, HPV58, and HPV52 were the most common types of HR-HPV infections, while CP8304, HPV11, and HPV6 were the most common types of LR-HPV infections. Among the multiple infection groups, HPV16 was the most common type of co-infection. Furthermore, the prevalence of HPV infections varied among different age groups. Age-specific prevalence of HPV exhibited two peaks in the youngest age group and in the group aged 50-60 years. CONCLUSION: HPV16, 58, 52, 33, 53, and 18 were the most common types in the general female population. The prevalence of HPV infection varied among different age groups. This study provides guidance for future HPV-based cervical cancer screening tests and prophylactic HPV vaccinations in China.

Evaluation of triage strategies for high-risk human papillomavirus-positive women in cervical cancer screening: A multicenter randomized controlled trial in different resource settings in China.

Objective: We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus (hrHPV)-positive women in primary healthcare settings in China. Methods: This study was undertaken in 11 rural and 9 urban sites. Women aged 35-64 years old were enrolled. HrHPV-positive women were randomly allocated to liquid-based cytology (LBC), visual inspection with acetic acid and Lugol's iodine (VIA/VILI) (rural only) triage, or directly referred to colposcopy (direct COLP). At 24 months, hrHPV testing, LBC and VIA/VILI were conducted for combined screening. Results: In rural sites, 1,949 hrHPV-positive women were analyzed. A total of 852, 218 and 480 women were randomly assigned to direct COLP, LBC and VIA/VILI. At baseline, colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%. LBC (n=3 and n=7) or VIA/VILI (n=8 and n=26) could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia (CIN) 2 or worse and CIN3+ compared with direct COLP (n=14 and n=23). For the 24-month cumulative detection rate of CIN2+, VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP. When stratified by age, baseline LBC triage+ performed best (P<0.001), peaking among women aged 35-44 years (Ptrend=0.002). In urban sites, 1,728 women were hrHPV genotyping test positive. A total of 408, 571 and 568 women were randomly assigned to direct COLP for HPV16/18+, direct COLP for other hrHPV subtypes+, and LBC triage for other hrHPV subtypes+. LBC (n=12 and n=31) significantly decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ compared with direct COLP (n=14 and n=44). HPV16/18+ increased the 24-month cumulative detection rate of CIN2+ (17.89%, P<0.001). Conclusions: LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+ women and LBC triage for other hrHPV subtype+ women in urban settings might be feasible strategies.

A Five-Gene Expression Signature Predicts Ovarian Cancer Metastasis.

Ovarian cancer represents one of the most malignant gynecological tumors. Despite recent advances in treatment, ovarian cancer remains to be highly susceptible to metastasis. However, information concerning genome-wide gene expression profiles is limited to develop a metastasis-specific gene signature in ovarian cancer. In this work, we try to identify changes in gene expression profile that underlie ovarian cancer metastasis. The dataset GSE73168 deposited in the Gene Expression Omnibus (GEO) database was processed to identify differentially expressed genes (DEGs) between primary tumor and metastatic tumor samples. The weighted gene correlation network analysis (WGCNA) was conducted for modules related to ovarian cancer metastasis. Modular genes associated with ovarian cancer metastasis were summarized for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Receiver operating characteristic (ROC) curves were plotted to estimate the superiority of candidate genes in detecting ovarian cancer metastasis. The WGCNA yielded 25 co-expression network modules in the dataset GSE73168, and highly correlated genes with ovarian cancer metastasis were identified in the blue module. Twenty-two genes demonstrated differential expression between primary tumor and metastatic tumor samples, and two downregulated genes (P2RY13 and NKX6-1) and three upregulated genes (CD36, LOC57399 and RP11-587D21.4) of these 22 DEGs was also shown to correlate with ovarian cancer metastasis in the blue module. The area under the ROC curve verified these five DEGs as metastasis-specific genes for ovarian cancer. These results show P2RY13, NKX6-1, CD36, LOC57399 and RP11-587D21.4 serve as metastasis-specific genes for ovarian cancer.

MtSSPdb: The Medicago truncatula Small Secreted Peptide Database.

A growing number of small secreted peptides (SSPs) in plants are recognized as important regulatory molecules with roles in processes such as growth, development, reproduction, stress tolerance, and pathogen defense. Recent discoveries further implicate SSPs in regulating root nodule development, which is of particular significance for legumes. SSP-coding genes are frequently overlooked, because genome annotation pipelines generally ignore small open reading frames, which are those most likely to encode SSPs. Also, SSP-coding small open reading frames are often expressed at low levels or only under specific conditions, and thus are underrepresented in non-tissue-targeted or non-condition-optimized RNA-sequencing projects. We previously identified 4,439 SSP-encoding genes in the model legume Medicago truncatula To support systematic characterization and annotation of these putative SSP-encoding genes, we developed the M. truncatula Small Secreted Peptide Database (MtSSPdb; https://mtsspdb.noble.org/). MtSSPdb currently hosts (1) a compendium of M. truncatula SSP candidates with putative function and family annotations; (2) a large-scale M. truncatula RNA-sequencing-based gene expression atlas integrated with various analytical tools, including differential expression, coexpression, and pathway enrichment analyses; (3) an online plant SSP prediction tool capable of analyzing protein sequences at the genome scale using the same protocol as for the identification of SSP genes; and (4) information about a library of synthetic peptides and root and nodule phenotyping data from synthetic peptide screens in planta. These datasets and analytical tools make MtSSPdb a unique and valuable resource for the plant research community. MtSSPdb also has the potential to become the most complete database of SSPs in plants.

The association of different serum IgG4 levels with distinct clinical characteristics and treatment efficacy in patients with IgG4-related disease.

OBJECTIVSE: To explore the clinical characteristics and treatment efficacy of IgG4-related disease (IgG4-RD) patients with different levels of serum IgG4. METHODS: A total of 299 patients newly diagnosed with IgG4-RD were enrolled in this study. Patients were classified into four groups according to baseline serum IgG4 levels: Group A: normal concentration; Group B: > normal but <2× the upper reference limit (URL); Group C: between 2× and 5× the URL; Group D: >5× the URL. All patients were followed up for 12 months. The patients' clinical characteristics, laboratory parameters, plasmablasts/plasma cells and treatment efficacy were analysed. RESULTS: IgG4-RD patients with higher serum IgG4 levels had higher percentages of dacryoadenitis, sialadenitis, and autoimmune pancreatitis and a higher prevalence of allergy history, whereas patients with retroperitoneum and mediastinum lesions usually had lower serum IgG4 levels. In addition, the serum IgG4 re-elevation rate in Group D (19.4%) was higher than those in Group B (4.9%) and Group C (7.7%) (p=0.003 and p=0.020, respectively). Patients suffered fewer clinical relapses with a serum IgG4 reduction ≥50% of baseline serum IgG4 in Group B and ≥40% of baseline serum IgG4 in Group D (p=0.019 and p=0.043, respectively). In addition, the rate of clinical relapse in patients who received combination therapy with glucocorticoids and mycophenolate mofetil was 18.75% in Group D, which was higher than the rates in Groups B and C (0) (p=0.027). CONCLUSIONS: IgG4-RD patients with different levels of serum IgG4 exhibit different clinical characteristics and treatment responses.

Expression profile and bioinformatics analyses of circular RNAs in keloid and normal dermal fibroblasts.

Increasing evidence indicates that circular RNAs (circRNAs) play a crucial regulatory role in the pathogenesis of multiple diseases. However, no study has examined the potential biological function and expression profile of circRNAs in keloid dermal fibroblasts (KDFs). Therefore, the aim of this study to investigate the expression profile of circRNAs and analyze their role in KDFs. Bioinformatic analyses and high-throughput RNA sequencing technology were applied to explore the expression profile of circRNAs in 3 human KDFs and normal dermal fibroblasts (NDFs). The differentially expressed circRNAs were verified by reverse transcription PCR (RT-PCR), quantitative real-time-PCR (qRT-PCR) and Sanger sequencing. A circRNA-microRNA (miRNA)-mRNA interaction network was created using bioinformatics tools. Hsa_circ_0008259, was selected to confirm its function by qRT-PCR and Western blot. Collectively, 411 circRNAs, of which 206 were upregulated and 205 decreased, were found to be differentially expressed in KDFs and could bind to 2532 miRNA response elements (MREs). GO and KEGG pathways enrichment analyses showed that differentially expressed circRNAs were mainly involved in apoptosis, focal adhesion, PI3K-Akt and metabolic pathway, and may regulate the pathogenesis and development of keloid. Two candidate circRNAs (hsa_circRNA_0008259, hsa_circRNA_0005480) were verified to be significantly reduced in KDFs, and one candidate circRNA (hsa_circRNA_0002198) was significantly elevated in accordance with RNA-Seq data analysis. Overexpression of hsa_circRNA_0008259 inhibited type I and Ⅲ collagen expression. Taken together, our study demonstrates for the first time that circRNAs exhibits differential expression in KDFs, and may be key players in the pathogenesis of keloid, or act as biomarkers of keloid.

Partial-film mulch returns the same gains in yield and water use efficiency as full-film mulch with reduced cost and lower pollution: a meta-analysis.

BACKGROUND: Plastic film mulch is widely used to improve crop yield and water use efficiency (WUE, yield per unit evapotranspiration) in semi-arid regions. It is commonly applied as partial-film mulch (PM: at least 50% soil cover) or full-film mulch (FM: complete soil cover). The PM has lower economic and environmental cost; hence it would be a superior technology provided it delivers similar gains in yield and WUE in relation to FM. RESULTS: To solve contradictory results from individual studies, we compared FM and PM in a meta-analysis of 100 studies with 1881 comparisons (685 for wheat; 1196 for maize). Compared with bare ground, FM and PM both increased yield of wheat (20-26%) and maize (37-52%), and WUE of wheat (16-20%) and maize (38-48%), with statistically undistinguishable differences between PM and FM. The increases in crop yield and WUE were stronger at elevation > 1000 m, with annual precipitation<400 mm, and on loess soil, especially for maize. CONCLUSIONS: We concluded that partial-film mulch could replace full-film mulch to return similar yield and WUE improvement, with reduced cost and environmental pollution. © 2021 Society of Chemical Industry.

Elevated Serum IgG4 Was Found in Eosinophilic Granulomatosis With Polyangiitis.

OBJECTIVE: The aim was to determine the levels and clinical impact of immunoglobulin G4 (IgG4) and other IgG subclasses in a Chinese population with eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We enrolled 49 patients who had EGPA, 27 who had granulomatosis with polyangiitis (GPA), 31 who had microscopic polyangiitis (MPA), and 30 healthy controls (HCs). Serum IgG subclasses were measured using commercial immunonephelometric assays and compared among different groups. RESULTS: Fifteen EGPA patients (30.61%) had elevated IgG4 levels, based on a cutoff value of 135 mg/dL. In addition, 2 GPA patients (7.40%) and 1 MPA patient (3.33%) had elevated IgG4 levels. The EPGA group had a higher IgG4 level (65.60 mg/dL) than the GPA group (32.70 mg/dL, p = 0.0021), the MPA group (30 mg/dL, p = 0.0021), and the HC group (28.55 mg/dL, p = 0.0002). The EPGA group also had a higher IgG4/IgG ratio (0.0644) than the GPA group (0.0322, p = 0.13), the MPA group (0.0289, p = 0.0055), and the HC group (0.0212, p < 0.0001). CONCLUSIONS: Our results indicate that Chinese patients with EGPA have increased levels of serum IgG4. Further study is needed to determine the pathogenic role of IgG4 and IgG4 antineutrophil cytoplasmic antibodies in EGPA.

High-throughput sequencing identification of differentially expressed microRNAs in metastatic ovarian cancer with experimental validations.

BACKGROUND: Ovarian cancer (OC) is a common gynecological cancer and characterized by high metastatic potential. MicroRNAs (miRNAs, miRs) have the promise to be harnessed as prognostic and therapeutic biomarkers for OC. Herein, we sought to identify differentially expressed miRNAs and mRNAs in metastatic OC, and to validate them with functional experiments. METHODS: Differentially expressed miRNAs and mRNAs were screened from six pairs of primary OC tissues and metastatic tissues using a miRStar™ Human Cancer Focus miRNA and Target mRNA PCR Array. Then, gene expression profiling results were verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The binding affinity between miR-7-5p and TGFß2 was validated by dual-luciferase reporter assay. Expression of miR-7-5p and TGFß2 was manipulated to assess their roles in malignant phenotypes of highly metastatic HO-8910PM cells. RESULTS: MiRNA profiling and sequencing identified 12 miRNAs and 10 mRNAs that were differentially expressed in metastatic tissues. Gene ontology and Pathway analyses determined that 3 differentially expressed mRNAs (ITGB3, TGFß2 and TNC) were related to OC metastasis. The results of RT-qPCR confirmed that the decrease of miR-7-5p was most significant in OC metastasis, while TGFß2 was up-regulated in OC metastasis. Moreover, miR-7-5p targeted and negatively regulated TGFß2. MiR-7-5p overexpression accelerated HO-8910PM cell viability and invasion, and TGFß2 overexpression reversed the results. Meanwhile, simultaneous miR-7-5p and TGFß2 overexpression rescued the cell activities. CONCLUSIONS: This study characterizes differentially expressed miRNAs and mRNAs in metastatic OC, where miR-7-5p and its downstream target were most closely associated with metastatic OC. Overexpression of miR-7-5p targets and inhibits TGFß2 expression, thereby inhibiting the growth and metastasis of OC.

Bi and oxygen defects improved visible light photocatalysis with BiOBr nanosheets.

Bi metal attached BiOBr with oxygen defect (BiOBr(3)-Bi(x%, x = 10, 20, 30)) nanosheets was prepared via the hydrothermal process in this study. The different characterization techniques of x-ray diffraction, x-ray photoelectron spectrometer, electron spin resonance (ESR), field emission scanning electron microscope, and high resolution transmission electron microscope were used to distinguish the composition, crystal structure, and morphology of the samples. Under visible light irradiation, the BiOBr(3)-Bi(x%, x = 10, 20, 30) samples exhibited improved photocatalytic activity for the degradation of colored dyes (RhB) and colorless tetracycline hydrochloride. Such an improvement was ascribed to the widened visible light absorption and enhanced separation of the photogenerated electron-hole pairs because of the synergistic effect of oxygen vacancies and Bi metal with plasmon resonance effects. A possible photocatalytic mechanism of the quasi Z-scheme process was proposed on the basis of ESR measurements and radical-trapping experiments.

High levels of antibodies to citrullinated α-enolase peptide-1 (CEP-1) identify erosions and interstitial lung disease (ILD) in a Chinese rheumatoid arthritis cohort.

We evaluated the clinical performance of anti-CEP-1 in a Chinese rheumatoid arthritis (RA) cohort. A total of 264 subjects were tested, including 101 RA patients, 38 juvenile idiopathic arthritis (JIA) patients, 46 disease control (DC) and 79 healthy controls (HC). The presence of anti-CEP-1 in patients with RA, JIA, DCs and HC were 61.4%, 13.2%, 15.2% and 5.1%, respectively. Anti-CCP2 demonstrated the highest positive likelihood ratio of 10.11 in the diagnosis of RA, followed by RF (8.88) and anti-CEP-1 (5.82). Anti-CEP-1 positive RA patients displayed significantly higher DAS28 compared to anti-CEP-1 negative RA patients (p = .045). Significant associations were identified between anti-CEP-1 and joint erosions at anti-CEP-1 value of >124.78 U/ml (p = .0026) and between anti-CEP-1 and ILD at anti-CEP-1 value of >185.91 U/ml (p = .0222). Our findings indicate that anti-CEP-1 may not be able to replace anti-CCP2 for routine diagnosis for RA, but they may be helpful for subtyping of the disease.

Correlation Between Extended Leukocyte Differential Count and Coronary Artery Disease.

BACKGROUND: Leukocyte count is closely associated with the risk of coronary artery disease (CAD). Levels of leukocyte subpopulations in patients with CAD, however, remain largely unknown. METHODS: In this study, we compared the distributions and counts of 16 leukocyte subpopulations between 40 patients with CAD and 40 healthy controls using the CytoDiff flow cytometric system. RESULTS: Our results demonstrated significant increases in the frequencies and counts of all monocytes, immature granulocytes, and B-lymphocytes in patients with CAD, suggesting that the levels of these leukocyte subpopulations may serve as potential biomarkers for diagnosis of CAD. By contrast, the levels of cytotoxic T/natural killer lymphocytes were markedly decreased in patients with CAD. In addition, the levels of T/natural killer lymphocytes, noncytotoxic T-lymphocytes, mature neutrophils, total neutrophils, eosinophils, basophils, and T-cell blasts in CAD patients with elevated levels of cardiac troponin I (cTnI), an independent indicator for poor prognosis in CAD, were significantly different from those in CAD patients with normal levels of cTnI. These data may help in the screening for biomarkers to discriminate between stable and unstable patients with CAD. CONCLUSIONS: Collectively, our results provide a detailed distribution profile of leukocyte subpopulations in patients with CAD and suggest their possible clinical application in predicting the risk and severity of CAD.

Antibodies to phosphatidylserine/prothrombin (aPS/PT) enhanced the diagnostic performance in Chinese patients with antiphospholipid syndrome.

BACKGROUND: Increasing evidence has highlighted the role of non-criteria antiphospholipid antibodies (aPLs) as important supplements to the current criteria aPLs for the diagnosis of antiphospholipid syndrome (APS). In this retrospective study, we evaluated the clinical relevance of antibodies to phosphatidylserine/prothrombin (aPS/PT) in Chinese patients with APS. METHODS: A total of 441 subjects were tested, including 101 patients with primary APS (PAPS), 140 patients with secondary APS (SAPS), 161 disease controls (DCs) and 39 healthy controls (HCs). Serum IgG/IgM aPS/PT was determined by ELISA. RESULTS: The levels of IgG/IgM aPS/PT were significantly increased in patients with APS compared with DCs and HCs. IgG and IgM aPS/PT were present in 29.7% and 54.5% of PAPS, and 42.1% and 53.6% of SAPS, respectively. For diagnosis of APS, IgG aCL exhibited the highest positive likelihood ratio (LR+) of 21.60, followed by LA (13.84), IgG aß2GP1 (9.19) and IgG aPS/PT (8.49). aPS/PT was detected in 13.3% of seronegative PAPS patients and 31.3% of seronegative SAPS patients. LA exhibited the highest OR of 3.64 in identifying patients with thrombosis, followed by IgG aCL (OR, 2.63), IgG aPS/PT (OR, 2.55) and IgG aß2GP1 (OR, 2.33). LA and IgG aCL were correlated with both arterial and venous thrombosis, whereas IgG aPS/PT and IgG aß2GP1 correlated with venous or arterial thrombosis, respectively. CONCLUSIONS: Our findings suggest that the inclusion of IgG/IgM aPS/PT may enhance the diagnostic performance for APS, especially in those in whom APS is highly suspected, but conventional aPLs are repeatedly negative. In addition, IgG aPS/PT may contribute to identify patients at risk of thrombosis.

A Medicago truncatula Cystathionine-ß-Synthase-like Domain-Containing Protein Is Required for Rhizobial Infection and Symbiotic Nitrogen Fixation.

The symbiosis between leguminous plants and soil rhizobia culminates in the formation of nitrogen-fixing organs called nodules that support plant growth. Two Medicago truncatula Tnt1-insertion mutants were identified that produced small nodules, which were unable to fix nitrogen effectively due to ineffective rhizobial colonization. The gene underlying this phenotype was found to encode a protein containing a putative membrane-localized domain of unknown function (DUF21) and a cystathionine-ß-synthase domain. The cbs1 mutants had defective infection threads that were sometimes devoid of rhizobia and formed small nodules with greatly reduced numbers of symbiosomes. We studied the expression of the gene, designated M truncatula Cystathionine-ß-Synthase-like1 (MtCBS1), using a promoter-ß-glucuronidase gene fusion, which revealed expression in infected root hair cells, developing nodules, and in the invasion zone of mature nodules. An MtCBS1-GFP fusion protein localized itself to the infection thread and symbiosomes. Nodulation factor-induced Ca(2+) responses were observed in the cbs1 mutant, indicating that MtCBS1 acts downstream of nodulation factor signaling. MtCBS1 expression occurred exclusively during Medicago-rhizobium symbiosis. Induction of MtCBS1 expression during symbiosis was found to be dependent on Nodule Inception (NIN), a key transcription factor that controls both rhizobial infection and nodule organogenesis. Interestingly, the closest homolog of MtCBS1, MtCBS2, was specifically induced in mycorrhizal roots, suggesting common infection mechanisms in nodulation and mycorrhization. Related proteins in Arabidopsis have been implicated in cell wall maturation, suggesting a potential role for CBS1 in the formation of the infection thread wall.

Dickkopf-4 is frequently overexpressed in epithelial ovarian carcinoma and promotes tumor invasion.

BACKGROUND: Dickkopf-4 (DKK4), a member of DKK family, appears to be a divergent protein. It remained multi-biological functions in carcinogenesis. The effect of DKK4 on the ovarian cancer cells remains unclear. This study detected the clinical significance of DKK4 in epithelial ovarian cancer (EOC) patients and its role in invasion. METHODS: QRT-PCR and western blot analysis were used to examine the levels of DKK4 mRNA and protein in 33 EOC tissues and 33 benign ovarian tumors. Immunohistochemical analysis was performed to assess DKK4 expression in 239 EOC samples. siRNA-mediated DKK4 silence was conducted. Transwell assay was used to detect the invasive ability. Phalloidin was used to stain the formations of actin filaments. RESULTS: The expressions of DKK4 mRNA and protein were elevated in EOC tissues as compared with those in benign ovarian tumors (p = 0.001 and <0.0001 respectively). Immunohistochemical results showed the strong expression of DKK4 protein was positively associated with late FIGO stage (p = 0.005) and poor disease free survival in univariate and multivariate analysis (p < 0.0001 and p = 0.001, respectively). SiRNA-mediated DKK4 knockdown inhibited cell invasive ability (all p < 0.0001) and the formations of actin filaments. DKK4 could promote the phosphration of c-JUN and JNK (p < 0.0001 and p = 0.001, respectively). CONCLUSIONS: Our results indicated that DKK4 might be contributed to predicting EOC progression and prognosis. DKK4 could promote the invasion of EOC through JNK activation.

Retrospective evaluation of the clinical utility of serological biomarkers in Chinese patients with inflammatory bowel disease: 2-year clinical experience.

BACKGROUND: Antibodies to saccharomyces cerevisiae (ASCA), antibodies to perinuclear anti-neutrophil cytoplasmic (pANCA), pancreatic autoantibodies (PAB) and antibodies against intestinal goblet cells (GAB) are important in diagnosing Crohn's disease (CD) and ulcerative colitis (UC). However, little is known about their diagnostic value in real clinical practice in China. This retrospective study aimed to present our 2-year clinical experience with those biomarkers in diagnosis of CD and UC. METHODS: A total of 140 patients with UC, 128 patients with CD, and 224 patients with intestinal associated diseases as disease controls were included. Serum ASCA were determined by ELISA. Serum pANCA, GAB, and PAB were tested by indirect immunofluorescent assay. Retrospective review of laboratory results and clinical information was performed. RESULTS: ASCA and ASCA+/pANCA- showed poor abilities in differentiating CD from UC, CD from intestinal Behçet's disease (BD), or CD from intestinal tuberculosis (ITB). In contrast, PAB exhibited good capacities in differentiating CD from UC, CD from intestinal BD, and CD from ITB. IgG pANCA demonstrated a high sensitivity and specificity in differentiating UC from CD. pANCA+/ASCA- or pANCA+/PAB- displayed a high sensitivity and specificity in differentiating UC from CD. GAB showed poor potential in differentiating UC from CD. PAB were positively correlated with early disease onset, ileocolonic disease, and perianal disease in CD patients. CONCLUSIONS: Our data suggest that pANCA and PAB are helpful in diagnosis of UC and CD, respectively, while ASCA and GAB were not. Our findings indicate a clear need for additional biomarkers for diagnosis of CD in China.

Clinical performance of antibodies to prothrombin and thrombin in Chinese patients with antiphospholipid syndrome: potential interest in discriminating patients with thrombotic events and non-thrombotic events.

A hallmark feature of antiphospholipid syndrome (APS) is the presence of a wide spectrum of antiphospholipid antibodies. In this study, we evaluated the clinical relevance of antibodies to prothrombin (PT) (aPT) and thrombin (aThr) in Chinese patients with APS. A total of 229 subjects were tested, including 86 patients with APS [35 patients with primary APS (PAPS), 51 patients with APS associated with other diseases (APSAOD)], 104 patients with non-APS diseases (disease controls), and 39 healthy controls. Serum IgG/IgM/IgA aPT and aThr were determined by ELISA. The levels of both IgG/IgM/IgA aPT and IgG/IgM/IgA aThr were significantly increased in patients with PAPS and APSAOD compared with patients with non-APS thrombosis and non-APS PRM, and HC. Both IgG aPT and IgG aThr exhibited promising diagnostic potentials for APS with sensitivities and specificities of 16.3 and 95.8% (IgG aPT), and 19.8 and 99.3% (IgG aThr), respectively. Importantly, both IgG aPT (OR 4.06; 95% CI 1.49-11.05) and IgG aThr (OR 4.49; 95% CI 1.62-12.45) were significantly correlated with arterial, but not venous, thrombotic events. Our findings highlighted that IgG aPT and IgG aThr could serve as promising biomarkers to identify patients at risk of arterial thrombosis in China.