Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma.

BACKGROUND: The Alcian blue (AB) and periodic acid Schiff (PAS) stains are representative mucus markers in gastric signet ring cell carcinoma (SRCC). They are low-cost special staining methods used to detect acidic mucus and neutral mucus, respectively. However, the clinical importance of the special combined AB and PAS stain is unclear. AIM: To investigate AB expression, PAS expression and the AB-to-PAS (A/P) ratio in gastric SRCC patients and to assess patient prognosis. METHODS: Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS, and signet ring cell positivity was assessed quantitatively. Immunohistochemical staining for Ki67, protein 53 (P53) and human epidermal growth factor receptor 2 (HER2) was performed simultaneously. The cancer-specific survival (CSS) rate was estimated via Kaplan-Meier analysis. Cox proportional hazards models were used for univariate and multivariate survival analyses. RESULTS: Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup (P < 0.001). The 3-year CSS rate in the A/P ≤ 0.5 group was significantly greater than that in the A/P > 0.5 group (P = 0.042). Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter, lymph node metastasis, vessel carcinoma embolus, tumor stage, the A/P ratio and the expression of Ki67, P53 and the PAS. Cox multivariate regression analysis confirmed that low PAS expression [hazard ratio (HR) = 3.809, 95% confidence interval (CI): 1.563-9.283, P = 0.003] and large tumor diameter (HR = 2.761, 95%CI: 1.086-7.020, P = 0.033) were independent risk factors for poor prognosis. CONCLUSION: A/P > 0.5 is potentially a risk factor for prognosis, and low PAS expression is an independent risk factor in the prognosis of gastric SRCC. PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

Anti-inflammatory effect of echinacoside in collagen-induced arthritis via Nrf2/Drp1 pathway.

BACKGROUND: Oxidative damage plays an important role in the progression of rheumatoid arthritis (RA). Emerging research evidence suggests that natural antioxidants may effectively ameliorate this disease. OBJECTIVES: To investigate the therapeutic effect of echinacoside (ECH) in a collagen-induced arthritis (CIA) mouse model and thus elucidate the underlying molecular mechanism in RA. MATERIAL AND METHODS: Collagen-induced arthritis mice were intraperitoneally administered 1% dimethyl sulfoxide (DMSO) (control) or 0.6 mg of ECH every other day for 1 month. Arthritis scores and the number of affected paws were assessed. On day 60, mice were euthanized, synovial tissue specimens were obtained, and serum interleukin (IL)-6 and IL-1â expression levels were measured. Mitochondrial morphologies, reactive oxygen species (ROS) content, expression of dynamin-related protein 1 (Drp1), IL-6, nod-like receptor protein 3 (NLRP3), kelch-like ECH-associated protein 1 (Keap1), and nuclear factor-erythroid-2-related factor 2 (Nrf2) contents in synovium were analyzed and compared between DMSOand ECH-treated CIA mice. RESULTS: Following ECH treatment, mitochondria of CIA-induced mice were found to be elongated, while their arthritis scores, inflammation and the number of affected paws, and the expression levels of Drp1, NLRP3, IL-6, ROS, and Keap1 were all found to be significantly reduced. Conversely, the level of antioxidant factor Nrf2 was found to be elevated. Further, mitochondrial fission was found to be inhibited in synovial tissues. CONCLUSIONS: Our findings validate the therapeutic efficacy of ECH in the CIA mouse model. Echinacoside may suppress oxidative stress and inhibit inflammation by regulating the Nrf2/Drp1 pathway, thus supporting its utility in the treatment of RA.

Establishment and Advances of Third-Generation Hybrid Rice Technology: A Review.

Rice (Oryza sativa L.) is one of the most important food crops worldwide. The utilisation of heterosis (hybrid vigour) has played a significant role in increasing rice yield and ensuring food supply. Over the past 50 years, the first-generation three-line system based on cytoplasmic male sterility, and the second-generation two-line system based on environment-sensitive genic male sterility (EGMS), have been widely applied in hybrid rice production. However, the three-line system is restricted by the matching relationship among the three parental lines and allows only ~ 2-5% of germplasms to be explored for elite combinations. The environmental sensitivity of EGMS lines has posed serious risks to the production of hybrid seeds. These factors have hindered the development and applications of hybrid rice. Third-generation hybrid rice technology (TGHRT) is based on environment-insensitive genic male sterility, which can effectively overcome the intrinsic problems of the three-line and two-line systems. Since the establishment of TGHRT, numerous findings and innovations have been reported. This paper gives a brief review of traditional hybrid rice technologies and discusses the establishment of TGHRT, technical innovations in TGHRT, and future research that is necessary to promote the wide application of TGHRT in rice production.

The ribosomal protein P0A is required for embryo development in rice.

BACKGROUND: The P-stalk is a conserved and vital structural element of ribosome. The eukaryotic P-stalk exists as a P0-(P1-P2)2 pentameric complex, in which P0 function as a base structure for incorporating the stalk onto 60S pre-ribosome. Prior studies have suggested that P0 genes are indispensable for survival in yeast and animals. However, the functions of P0 genes in plants remain elusive. RESULTS: In the present study, we show that rice has three P0 genes predicted to encode highly conserved proteins OsP0A, OsP0B and OsP0C. All of these P0 proteins were localized both in cytoplasm and nucleus, and all interacted with OsP1. Intriguingly, the transcripts of OsP0A presented more than 90% of the total P0 transcripts. Moreover, knockout of OsP0A led to embryo lethality, while single or double knockout of OsP0B and OsP0C did not show any visible defects in rice. The genomic DNA of OsP0A could well complement the lethal phenotypes of osp0a mutant. Finally, sequence and syntenic analyses revealed that OsP0C evolved from OsP0A, and that duplication of genomic fragment harboring OsP0C further gave birth to OsP0B, and both of these duplication events might happen prior to the differentiation of indica and japonica subspecies in rice ancestor. CONCLUSION: These data suggested that OsP0A functions as the predominant P0 gene, playing an essential role in embryo development in rice. Our findings highlighted the importance of P0 genes in plant development.

Establishment and validation of a nomogram model for predicting distant metastasis in medullary thyroid carcinoma: An analysis of the SEER database based on the AJCC 8th TNM staging system.

Objective: Medullary thyroid carcinoma (MTC) patients with distant metastases frequently present a relatively poor survival prognosis. Our main purpose was developing a nomogram model to predict distant metastases in MTC patients. Methods: This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database. Data of 807 MTC patients diagnosed from 2004 to 2015 who undergone total thyroidectomy and neck lymph nodes dissection was included in our study. Independent risk factors were screened by univariate and multivariate logistic regression analysis successively, which were used to develop a nomogram model predicting for distant metastasis risk. Further, the log-rank test was used to compare the differences of Kaplan-Meier curves of cancer-specific survival (CSS) in different M stage and each independent risk factor groups. Results: Four clinical parameters including age > 55 years, higher T stage (T3/T4), higher N stage (N1b) and lymph node ratio (LNR) > 0.4 were significant for distant metastases at the time of diagnosis in MTC patients, and were selected to develop a nomogram model. This model had satisfied discrimination with the AUC and C-index of 0.894, and C-index was confirmed to be 0.878 through bootstrapping validation. A decision curve analysis (DCA) was subsequently made to evaluate the feasibility of this nomogram for predicting distant metastasis. In addition, CSS differed by different M stage, T stage, N stage, age and LNR groups. Conclusions: Age, T stage, N stage and LNR were extracted to develop a nomogram model for predicting the risk of distant metastases in MTC patients. The model is of great significance for clinicians to timely identify patients with high risk of distant metastases and make further clinical decisions.

Ornithine δ-aminotransferase OsOAT is critical for male fertility and cold tolerance during rice plant development.

Cold stress is a major factor limiting the production and geographical distribution of rice (Oryza sativa) varieties. However, the molecular mechanisms underlying cold tolerance remain to be elucidated. Here, we report that ornithine δ-aminotransferase (OsOAT) contributes to cold tolerance during the vegetative and reproductive development of rice. osoat mutant was identified as a temperature-sensitive male sterile mutant with deformed floral organs and seedlings sensitive to cold stress. Comparative transcriptome analysis showed that OsOAT mutation and cold treatment of the wild-type plant led to similar changes in the global gene expression profiles in anthers. OsOAT genes in indica rice Huanghuazhan (HHZ) and japonica rice Wuyungeng (WYG) are different in gene structure and response to cold. OsOAT is cold-inducible in WYG but cold-irresponsive in HHZ. Further studies showed that indica varieties carry both WYG-type and HHZ-type OsOAT, whereas japonica varieties mostly carry WYG-type OsOAT. Cultivars carrying HHZ-type OsOAT are mainly distributed in low-latitude regions, whereas varieties carrying WYG-type OsOAT are distributed in both low- and high-latitude regions. Moreover, indica varieties carrying WYG-type OsOAT generally have higher seed-setting rates than those carrying HHZ-type OsOAT under cold stress at reproductive stage, highlighting the favorable selection for WYG-type OsOAT during domestication and breeding to cope with low temperatures.

Clinical laboratory evaluation of COVID-19.

COVID-19, caused by SARS-CoV-2, is a highly infectious disease, and clinical laboratory detection has played important roles in its diagnosis and in evaluating progression of the disease. Nucleic acid amplification testing or gene sequencing can serve as pathogenic evidence of COVID-19 diagnosing for clinically suspected cases, and dynamic monitoring of specific antibodies (IgM, IgA, and IgG) is an effective complement for false-negative detection of SARS-CoV-2 nucleic acid. Antigen tests to identify SARS-CoV-2 are recommended in the first week of infection, which is associated with high viral loads. Additionally, many clinical laboratory indicators are abnormal as the disease evolves. For example, from moderate to severe and critical cases, leukocytes, neutrophils, and the neutrophil-lymphocyte ratio increase; conversely, lymphocytes decrease progressively but are over activated. LDH, AST, ALT, CK, high-sensitivity troponin I, and urea also increase progressively, and increased D-dimer is an indicator of severe disease and an independent risk factor for death. Severe infection leads to aggravation of inflammation. Inflammatory biomarkers and cytokines, such as CRP, SAA, ferritin, IL-6, and TNF-α, increase gradually. High-risk COVID-19 patients with severe disease, such as the elderly and those with underlying diseases (cardiovascular disease, diabetes, chronic respiratory disease, hypertension, obesity, and cancer), should be monitored dynamically, which will be helpful as an early warning of serious diseases.

Overexpression of OsMed16 Inhibits the Growth of Rice and Causes Spontaneous Cell Death.

The Mediator complex transduces information from the DNA-bound transcription factors to the RNA polymerase II transcriptional machinery. Research on plant Mediator subunits has primarily been performed in Arabidopsis, while very few of them have been functionally characterized in rice. In this study, the rice Mediator subunit 16, OsMed16, was examined. OsMed16 encodes a putative protein of 1301 amino acids, which is longer than the version previously reported. It was expressed in various rice organs and localized to the nucleus. The knockout of OsMed16 resulted in rice seedling lethality. Its overexpression led to the retardation of rice growth, low yield, and spontaneous cell death in the leaf blade and sheath. RNA sequencing suggested that the overexpression of OsMed16 altered the expression of a large number of genes. Among them, the upregulation of some defense-related genes was verified. OsMed16 can regulate the expression of a wealth of genes, and alterations in its expression have a profound impact on plant growth, development, and defense responses in rice.

Subdural drainage techniques for single burr-hole evacuation of chronic subdural hematoma: two drains frontal-occipital position versus one drain frontal position.

OBJECTIVE: Burr-hole craniostomy with a closed drainage system is the most commonly used technique for chronic subdural hematoma(CSDH), but the reoperation rate for hematoma recurrence is still high. This retrospective study aimed to compare the complications and recurrence of two subdural drains placement with tips frontal-occipital position (TFOP) versus one subdural drain placement with tip frontal position(OFP) following single burr-hole evacuation for the treatment of chronic subdural hematoma(CSDH). METHODS: The authors analyzed data of all CSDH patients who underwent single burr-hole surgery with placement of subdural closed-drainage system(TFOP or OFP techniques) between January 2013 and December 2017. Data analysis included general patient data, complications, recurrence and clinical outcome. RESULTS: A total of 331 patients were included(85 TFOP and 246 OFP). The TFOP group and OFP group were statistically comparable with respect to baseline characteristics except for preoperative Markwalder score (p = 0.019). Midline shift and subdural fluid thickness on first postoperative day were greater in OFP group than the TFOP group (p = 0.028; and p = 0.007, respectively). In addition, patients with OFP had a lower percent of hematoma change after surgery and much more residual subdural air than those with TFOP (p = 0.001; and p < 0.001, respectively). Postoperative complications and clinical outcome between the two groups showed no significant differences. During the 3-month follow-up, the rate of hematoma recurrence was significantly lower among patients treated with TFOP than those treated with OFP (p = 0.039). CONCLUSIONS: The postoperative complications rate did not differ between TFOP group and OFP group for patients with CSDH. Considering the lower rate of recurrence, TFOP following single burr-hole evacuation might be a safe and promising option for CSDH treatment.

MiR529a controls plant height, tiller number, panicle architecture and grain size by regulating SPL target genes in rice (Oryza sativa L.).

Rice is one of the most important food crops in the world. Breeding high-yield, multi-resistant and high-quality varieties has always been the goal of rice breeding. Rice tiller, panicle architecture and grain size are the constituent factors of yield, which are regulated by both genetic and environmental factors, including miRNAs, transcription factors, and downstream target genes. Previous studies have shown that SPL (SQUAMOSA PROMOTER BINDING-LIKE) transcription factors can control rice tiller, panicle architecture and grain size, which were regulated by miR156, miR529 and miR535. In this study, we obtained miR529a target mimicry (miR529a-MIMIC) transgenic plants to investigate plant phenotypes, physiological and molecular characteristics together with miR529a overexpression (miR529a-OE) and wild type (WT) to explore the function of miR529a and its SPL target genes in rice. We found that OsSPL2, OsSPL17 and OsSPL18 at seedling stage were regulated by miR529a, but there had complicated mechanism to control plant height. OsSPL2, OsSPL16, OsSPL17 and SPL18 at tillering stage were regulated by miR529a to control plant height and tiller number. And panicle architecture and grain size were controlled by miR529a through altering the expression of all five target genes OsSPL2, OsSPL7, OsSPL14, OsSPL16, OsSPL17 and OsSPL18. Our study suggested that miR529a might control rice growth and development by regulating different SPL target genes at different stages, which could provide a new method to improve rice yield by regulating miR529a and its SPL target genes.

Clinical characteristics and prognostic risk factors of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV).

OBJECTIVE: The complement alternative pathway is involved in the development of AVV. Several studies showed that AVV patients with low serum complement C3 (sC3) levels tend to have a poor prognosis. The aim of this study was to determine whether low sC3 measured at AAV onset is a risk factor for survival prognosis in patients with AVV, and further identified other potential risk factors for predicting patient survival prognosis. METHODS: A retrospective analysis of 52 newly onset AAV patients was performed. The clinical parameters of the AAV patients were collected. The laboratory parameters before immunosuppressive treatment were evaluated. According to the level of sC3, the patients were divided into low sC3 group (n = 19) and normal sC3 group (n = 33). Disease outcome measures included end-stage renal disease (ESRD) or death. The clinical parameters and survival rate between the two groups were compared. Spearson correlation analysis was used to analyze the correlation between sC3 and other laboratory parameters. RESULTS: Significant differences were found regarding Birmingham Vasculitis Activity Score (BVAS), sC3, sC4, lactate dehydrogenase, blood urea nitrogen, procalcitonin (PCT), and estimated glomerular filtration rate (eGFR) between the two groups (p = 0.006, 0.000, 0.001, 0.049, 0.019, 0.000 and 0.045, respectively). The survival rate of the low sC3 group was significantly lower than that of the normal sC3 group (Log Rank Chi-square = 4.416, P = 0.036). Low sC3 was significantly associated with lower sC4 (r = 0.570, P = 0.000), lower serum albumin (r = 0.311, P = 0.025), lower eGFR (r = 0.289, P = 0.037), higher PCT (r = -0.566, P = 0.000), and higher lactate dehydrogenase (r = -0.323, P = 0.019). CONCLUSION: This retrospective study demonstrates that AAV patients with low sC3 level at diagnosis tend to have lower baseline eGFR and poorer survival prognosis than those of the normal sC3 level. Furthermore, the high procalcitonin (PCT), low serum albumin and high lactate dehydrogenase in AVV patients may be predictors of poor prognosis.

OsMYB80 Regulates Anther Development and Pollen Fertility by Targeting Multiple Biological Pathways.

Pollen development is critical to the reproductive success of flowering plants, but how it is regulated is not well understood. Here, we isolated two allelic male-sterile mutants of OsMYB80 and investigated how OsMYB80 regulates male fertility in rice. OsMYB80 was barely expressed in tissues other than anthers, where it initiated the expression during meiosis, reached the peak at the tetrad-releasing stage and then quickly declined afterward. The osmyb80 mutants exhibited premature tapetum cell death, lack of Ubisch bodies, no exine and microspore degeneration. To understand how OsMYB80 regulates anther development, RNA-seq analysis was conducted to identify genes differentially regulated by OsMYB80 in rice anthers. In addition, DNA affinity purification sequencing (DAP-seq) analysis was performed to identify DNA fragments interacting with OsMYB80 in vitro. Overlap of the genes identified by RNA-seq and DAP-seq revealed 188 genes that were differentially regulated by OsMYB80 and also carried an OsMYB80-interacting DNA element in the promoter. Ten of these promoter elements were randomly selected for gel shift assay and yeast one-hybrid assay, and all showed OsMYB80 binding. The 10 promoters also showed OsMYB80-dependent induction when co-expressed in rice protoplast. Functional annotation of the 188 genes suggested that OsMYB80 regulates male fertility by directly targeting multiple biological processes. The identification of these genes significantly enriched the gene networks governing anther development and provided much new information for the understanding of pollen development and male fertility.

GDSL esterase/lipases OsGELP34 and OsGELP110/OsGELP115 are essential for rice pollen development.

Pollen exine contains complex biopolymers of aliphatic lipids and phenolics. Abnormal development of pollen exine often leads to plant sterility. Molecular mechanisms regulating exine formation have been studied extensively but remain ambiguous. Here we report the analyses of three GDSL esterase/lipase protein genes, OsGELP34, OsGELP110, and OsGELP115, for rice exine formation. OsGELP34 was identified by cloning of a male sterile mutant gene. OsGELP34 encodes an endoplasmic reticulum protein and was mainly expressed in anthers during pollen exine formation. osgelp34 mutant displayed abnormal exine and altered expression of a number of key genes required for pollen development. OsGELP110 was previously identified as a gene differentially expressed in meiotic anthers. OsGELP110 was most homologous to OsGELP115, and the two genes showed similar gene expression patterns. Both OsGELP110 and OsGELP115 proteins were localized in peroxisomes. Individual knockout of OsGELP110 and OsGELP115 did not affect the plant fertility, but double knockout of both genes altered the exine structure and rendered the plant male sterile. OsGELP34 is distant from OsGELP110 and OsGELP115 in sequence, and osgelp34 and osgelp110/osgelp115 mutants were different in anther morphology despite both were male sterile. These results suggested that OsGELP34 and OsGELP110/OsGELP115 catalyze different compounds for pollen exine development.

Identification of late-stage pollen-specific promoters for construction of pollen-inactivation system in rice.

Large-scale production of male sterile seeds can be achieved by introducing a fertility-restoration gene linked with a pollen-killer gene into a recessive male sterile mutant. We attempted to construct this system in rice by using a late-stage pollen-specific (LSP) promoter driving the expression of maize α-amylase gene ZM-AA1. To obtain such promoters in rice, we conducted comparative RNA-seq analysis of mature pollen with meiosis anther, and compared this with the transcriptomic data of various tissues in the Rice Expression Database, resulting in 269 candidate LSP genes. Initial test of nine LSP genes showed that only the most active OsLSP3 promoter could drive ZM-AA1 to disrupt pollen. We then analyzed an additional 22 LSP genes and found 12 genes stronger than OsLSP3 in late-stage anthers. The promoters of OsLSP5 and OsLSP6 showing higher expression than OsLSP3 at stages 11 and 12 could drive ZM-AA1 to inactivate pollen, while the promoter of OsLSP4 showing higher expression at stage 12 only could not drive ZM-AA1 to disrupt pollen, suggesting that strong promoter activity at stage 11 was critical for pollen inactivation. The strong pollen-specific promoters identified in this study provided valuable tools for genetic engineering of rice male sterile system for hybrid rice production.

The plant-specific ABERRANT GAMETOGENESIS 1 gene is essential for meiosis in rice.

Meiotic recombination plays a central role in maintaining genome stability and increasing genetic diversity. Although meiotic progression and core components are widely conserved across kingdoms, significant differences remain among species. Here we identify a rice gene ABERRANT GAMETOGENESIS 1 (AGG1) that controls both male and female gametogenesis. Cytological and immunostaining analysis showed that in the osagg1 mutant the early recombination processes and synapsis occurred normally, but the chiasma number was dramatically reduced. Moreover, OsAGG1 was found to interact with ZMM proteins OsHEI10, OsZIP4, and OsMSH5. These results suggested that OsAGG1 plays an important role in crossover formation. Phylogenetic analysis showed that OsAGG1 is a plant-specific protein with a highly conserved N-terminal region. Further genetic and protein interaction analyses revealed that the conserved N-terminus was essential for the function of the OsAGG1 protein. Overall, our work demonstrates that OsAGG1 is a novel and critical component in rice meiotic crossover formation, expanding our understanding of meiotic progression. This study identified a plant-specific gene ABERRANT GAMETOGENESIS 1 that is required for meiotic crossover formation in rice. The conserved N-terminus of the AGG1 protein was found to be essential for its function.

Lectin receptor kinase OsLecRK-S.7 is required for pollen development and male fertility.

Pollen grains are covered by exine that protects the pollen from stress and facilitates pollination. Here we isolated a male sterile mutant s13283 in rice exhibiting aborted pollen with abnormal exine and defective aperture. The mutant gene encodes a novel plasma membrane-localized legume-lectin receptor kinase that we named OsLecRK-S.7. OsLecRK-S.7 was expressed at different levels in all tested tissues and throughout anther development. In vitro kinase assay showed OsLecRK-S.7 capable of autophosporylation. Mutation in s13283 (E560K) and mutation of the conserved ATP binding site (K418E) both knocked out the kinase activity. Mass spectrometry showed Thr376 , Ser378 , Thr386 , Thr403 , and Thr657 to be the autophosphorylation sites. Mutation of individual autophosphorylation site affected the in vitro kinase activity to different degrees, but did not abolish the gene function in fertility complementation. oslecrk-s.7 mutant plant overexpressing OsLecRK-S.7 recovered male fertility but showed severe growth retardation with reduced number of tillers, and these phenotypes were abolished by E560K or K418E mutation. The results indicated that OsLecRK-S.7 was a key regulator of pollen development.

Inhibition of DNM1L and mitochondrial fission attenuates inflammatory response in fibroblast-like synoviocytes of rheumatoid arthritis.

Mitochondrial fission and fusion are important for mitochondrial function, and dynamin 1-like protein (DNM1L) is a key regulator of mitochondrial fission. We investigated the effect of mitochondrial fission on mitochondrial function and inflammation in fibroblast-like synoviocytes (FLSs) during rheumatoid arthritis (RA). DNM1L expression was determined in synovial tissues (STs) from RA and non-RA patients. FLSs were isolated from STs and treated with a DNM1L inhibitor (mdivi-1, mitochondrial division inhibitor 1) or transfected with DNM1L-specific siRNA. Mitochondrial morphology, DNM1L expression, cell viability, mitochondrial membrane potential, reactive oxygen species (ROS), apoptosis, inflammatory cytokine expression and autophagy were examined. The impact of mdivi-1 treatment on development and severity of collagen-induced arthritis (CIA) was determined in mice. Up-regulated DNM1L expression was associated with reduced mitochondrial length in STs from patients with RA and increased RA severity. Inhibition of DNM1L in FLSs triggered mitochondrial depolarization, mitochondrial elongation, decreased cell viability, production of ROS, IL-8 and COX-2, and increased apoptosis. DNM1L deficiency inhibited IL-1ß-mediated AKT/IKK activation, NF-κBp65 nuclear translocation and LC3B-related autophagy, but enhanced NFKBIA expression. Treatment of CIA mice with mdivi-1 decreased disease severity by modulating inflammatory cytokine and ROS production. Our major results are that up-regulated DNM1L and mitochondrial fission promoted survival, LC3B-related autophagy and ROS production in FLSs, factors that lead to inflammation by regulating AKT/IKK/NFKBIA/NF-κB signalling. Thus, inhibition of DNM1L may be a new strategy for treatment of RA.

The ATP-binding cassette (ABC) transporter OsABCG3 is essential for pollen development in rice.

BACKGROUND: The pollen wall, which protects male gametophyte against various stresses and facilitates pollination, is essential for successful reproduction in flowering plants. The pollen wall consists of gametophyte-derived intine and sporophyte-derived exine. From outside to inside of exine are tectum, bacula, nexine I and nexine II layers. How these structural layers are formed has been under extensive studies, but the molecular mechanisms remain obscure. RESULTS: Here we identified two osabcg3 allelic mutants and demonstrated that OsABCG3 was required for pollen development in rice. OsABCG3 encodes a half-size ABCG transporter localized on the plasma membrane. It was mainly expressed in anther when exine started to form. Loss-function of OsABCG3 caused abnormal degradation of the tapetum. The mutant pollen lacked the nexine II and intine layers, and shriveled without cytoplasm. The expression of some genes required for pollen wall formation was examined in osabcg3 mutants. The mutation did not alter the expression of the regulatory genes and lipid metabolism genes, but altered the expression of lipid transport genes. CONCLUSIONS: Base on the genetic and cytological analyses, OsABCG3 was proposed to transport the tapetum-produced materials essential for pollen wall formation. This study provided a new perspective to the genetic regulation of pollen wall development.

Role of miR-24, Furin, and Transforming Growth Factor-ß1 Signal Pathway in Fibrosis After Cardiac Infarction.

BACKGROUND Cardiac fibrosis after primary infarction is a type of pathological phenomena as shown by increased collagen in myocardial cells. Transforming growth factor (TGF)-ß1 is a critical factor participating in myocardial fibrosis. A previous study has shown the inhibitory role on TGF-ß1 by microRNA-24 (miR-24) via targeting Furin. This study thus investigated the role of miR-24 and Furin/TGF-ß1 in rat myocardial fibrosis. MATERIAL AND METHODS A total of 40 adult SD rats (both males and females) were prepared for myocardial infarction model by ligating the descending branch of left coronary artery after anesthesia. HE staining was performed to observe myocardial fibrosis after 1, 2, and 4 weeks. Tissue RNA was extracted to detect mRNA levels of Furin, TGF-ß1, and miR-24 by real-time PCR. Western blotting was used to quantify protein expression of Furin and TGF-ß1 in myocardial tissues. RESULTS Increased connective tissues were observed in myocardial tissues at 4 weeks after infarction by HE staining, which also revealed widening of the intra-myocardial cleft, along with more inflammatory cells and fibroblast hypertrophy. miR-24 expression was significantly depressed at 2 and 4 weeks after cardiac infarction (p<0.05). mRNA levels of Furin and TGF-ß1 were elevated after infarction (p<0.05). With prolonged time periods of myocardial infarction, protein levels of Furin and TGF-ß1 were further increased. The level of miR-24 was positively correlated with left ventricular end-diastolic diameter, left ventricular systolic diameter, and left ventricular ejection fraction. However, the level of Furin or TGF-ß1 was negatively correlated with the above parameters. CONCLUSIONS This study demonstrated the important role of abnormal expression of miR-24 in myocardial fibrosis after infarction, and may provide drug targets for treating myocardial fibrosis.

An ABC transporter, OsABCG26, is required for anther cuticle and pollen exine formation and pollen-pistil interactions in rice.

Wax, cutin and sporopollenin are essential components for the formation of the anther cuticle and the pollen exine, respectively. Their lipid precursors are synthesized by secretory tapetal cells and transported to the anther and microspore surface for deposition. However, the molecular mechanisms involved in the formation of the anther cuticle and pollen exine are poorly understood in rice. Here, we characterized a rice male sterile mutant osabcg26. Molecular cloning and sequence analysis revealed a point mutation in the gene encoding an ATP binding cassette transporter G26 (OsABCG26). OsABCG26 was specifically expressed in the anther and pistil. Cytological analysis revealed defects in tapetal cells, lipidic Ubisch bodies, pollen exine, and anther cuticle in the osabcg26 mutant. Expression of some key genes involved in lipid metabolism and transport, such as UDT1, WDA1, CYP704B2, OsABCG15, OsC4 and OsC6, was significantly altered in osabcg26 anther, possibly due to a disturbance in the homeostasis of anther lipid metabolism and transport. Additionally, wild-type pollen tubes showed a growth defect in osabcg26 pistils, leading to low seed setting in osabcg26 cross-pollinated with the wild-type pollen. These results indicated that OsABCG26 plays an important role in anther cuticle and pollen exine formation and pollen-pistil interactions in rice.