Cryptochrome 1b represses gibberellin signaling to enhance lodging resistance in maize.

Maize (Zea mays L.) is one of the most important crops worldwide. Photoperiod, light quality, and light intensity in the environment can affect the growth, development, yield, and quality of maize. In Arabidopsis (Arabidopsis thaliana), cryptochromes are blue-light receptors that mediate the photocontrol of stem elongation, leaf expansion, shade tolerance, and photoperiodic flowering. However, the function of maize cryptochrome ZmCRY in maize architecture and photomorphogenic development remains largely elusive. The ZmCRY1b transgene product can activate the light signaling pathway in Arabidopsis and complement the etiolation phenotype of the cry1-304 mutant. Our findings show that the loss-of-function mutant of ZmCRY1b in maize exhibits more etiolation phenotypes under low blue light and appears slender in the field compared with wild-type plants. Under blue and white light, overexpression of ZmCRY1b in maize substantially inhibits seedling etiolation and shade response by enhancing protein accumulation of the bZIP transcription factors ELONGATED HYPOCOTYL 5 (ZmHY5) and ELONGATED HYPOCOTYL 5-LIKE (ZmHY5L), which directly upregulate the expression of genes encoding gibberellin (GA) 2-oxidase to deactivate GA and repress plant height. More interestingly, ZmCRY1b enhances lodging resistance by reducing plant and ear heights and promoting root growth in both inbred lines and hybrids. In conclusion, ZmCRY1b contributes blue-light signaling upon seedling de-etiolation and integrates light signals with the GA metabolic pathway in maize, resulting in lodging resistance and providing information for improving maize varieties.

Antinuclear Antibodies in Erythema Multiforme: Transient Occurrence During Acute Illness.

BACKGROUND: Children with target lesions are frequently diagnosed with erythema multiforme (EM). EM was not previously thought to be associated with any specific autoimmune serological abnormality. METHODS: We report the case of a 7-year-old girl who developed rashes all over her body with target shaped lesions. Based on clinical appearance and medical history, she was diagnosed with severe erythema multiforme and treated with methylprednisolone. Relevant laboratory tests were performed at admission. RESULTS: At the height of her infection, the antinuclear antibody (ANA) test showed a positive ANA with a titer of 1:100 (speckled pattern) and positive anti-SSA and anti-Ro-52 antibodies. Then she was adjusted for medication. After a week, the infection was relieved, and the re-examination was negative for ANA, anti-SSA, and anti-Ro-52 antibodies. CONCLUSIONS: In previously reported EM cases, ANA is generally not considered to be present. The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of EM infection. Its correlation with infection severity warrants further research on the mechanism of autoantibody formation in EM.

DNA-PKcs participated in hypoxic pulmonary hypertension.

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a common complication of chronic lung disease, which severely affects the survival and prognosis of patients. Several recent reports have shown that DNA damage and repair plays a crucial role in pathogenesis of pulmonary arterial hypertension. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a part of DNA-PK is a molecular sensor for DNA damage that enhances DSB repair. This study aimed to demonstrate the expression and potential mechanism of DNA-PKcs on the pathogenesis of HPH. METHODS: Levels of DNA-PKcs and other proteins in explants of human and rats pulmonary artery from lung tissues and pulmonary artery smooth muscle cells (PASMC) were measured by immunohistochemistry and western blot analysis. The mRNA expression levels of DNA-PKcs and NOR1 in PASMCs were quantified with qRT-PCR. Meanwhile, the interaction among proteins were detected by Co-immunoprecipitation (Co-IP) assays. Cell proliferation and apoptosis was assessed by cell counting kit-8 assay(CCK-8), EdU incorporation and flow cytometry. Rat models of HPH were constructed to verify the role of DNA-PKcs in pulmonary vascular remodeling in vivo. RESULTS: DNA-PKcs protein levels were both significantly up-regulated in explants of pulmonary artery from HPH models and lung tissues of patients with hypoxemia. In human PASMCs, hypoxia up-regulated DNA-PKcs in a time-dependent manner. Downregulation of DNA-PKcs by targeted siRNA or small-molecule inhibitor NU7026 both induced cell proliferation inhibition and cell cycle arrest. DNA-PKcs affected proliferation by regulating NOR1 protein synthesis followed by the expression of cyclin D1. Co-immunoprecipitation of NOR1 with DNA-PKcs was severely increased in hypoxia. Meanwhile, hypoxia promoted G2 + S phase, whereas the down-regulation of DNA-PKcs and NOR1 attenuated the effects of hypoxia. In vivo, inhibition of DNA-PKcs reverses hypoxic pulmonary vascular remodeling and prevented HPH. CONCLUSIONS: Our study indicated the potential mechanism of DNA-PKcs in the development of HPH. It might provide insights into new therapeutic targets for pulmonary vascular remodeling and pulmonary hypertension.

Analysis of Aeroallergens in Sichuan Province after the COVID-19 Epidemic.

BACKGROUND: Identifying the distribution and pattern of specific aeroallergens in Sichuan, China, after the corona-virus disease (COVID-19) epidemic and to provide a basis for future prevention and clinical treatment. METHODS: Serological tests for 10 types of aeroallergens were performed on 10,036 participants attending the West China Second University Hospital from January 2020 to January 2021. SPSS23.0 was used to statistically analyze their specific immunoglobulin E (sIgE) grades in different genders, various age groups, and different diseases. RESULTS: Of the 10,036 participants, 4,578 (45.62%) were allergic to at least one allergen. House dust had the highest sensitization rate (2,974, 29.63%), followed by Dermatophagoides farina (2,717, 27.07%) and Dermatophagoides pteronyssinus (2,611, 26.02%). Male and female participants had no significant difference in overall sensitization distributions. The prevalence differences between 0 - 3, 4 - 6, 7 - 9, 10 - 12, 13 - 15, and over 16-year-old age groups were statistically significant (p < 0.05), and the highest incidence age for children to be sensitive to aeroallergens was 4 - 6 years, respectively. Sensitization to D. pteronyssinus, D. farina, house dust, dog epithelium, and Alternaria alternata was more common in patients with rhinitis and asthma compared with bronchitis. CONCLUSIONS: Aeroallergens are important causes of respiratory-related allergic diseases, and the characteristics of allergen sensitization discovered in this study could help with inhalant allergy disease prevention, diagnosis, and management in the post-epidemic era.

Clinicopathological and prognostic significance of SWI/SNF complex subunits in undifferentiated gastric carcinoma.

BACKGROUND: The switch/sucrose nonfermentable (SWI/SNF) complex is an evolutionarily conserved chromatin remodeling complex that displays dysfunction in many tumors, especially undifferentiated carcinoma. Cancer stem cells (CSC), a special type of undifferentiated cancer cells with stem cell-like properties, play an essential role in tumor cell proliferation, invasion, and metastasis. In undifferentiated gastric carcinomas, the association of SWI/SNF complexes with clinicopathological features, CSC phenotype, and the prognosis is not fully understood. METHODS: We collected a cohort of 21 patients with undifferentiated/dedifferentiated gastric carcinoma. We next performed immunohistochemistry staining for the five subunits of the SWI/SNF complex (ARID1A, ARID1B, SMARCA2, SMARCA4, and SMARCB1), and four mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), as well as other markers such as p53, PD-L1, and cancer stem cell (CSC) markers (SOX2, SALL4). Then, we investigated the correlation of SWI/SNF complex subunits with clinicopathological characters and performed prognostic analysis. RESULTS: We observed SMARCA2 loss in 12 cases (57.14%), followed by ARID1A (5 cases, 23.81%) and SMARCA4 (3 cases, 14.29%). Fourteen cases (66.67%) lost any one of the SWI/SNF complex subunits, including 3 cases with SMARCA2 and ARID1A co-loss, and 3 cases with SMARCA2 and SMARCA4 co-loss. Correlation analysis revealed that the CSC phenotype occurred more frequently in the SWI/SNF complex deficient group (P = 0.0158). Survival analysis revealed that SWI/WNF complex deficiency, undifferentiated status, CSC phenotype, and the loss of SMARCA2 and SMARCA4 resulted in worse survival. Univariate and multivariate Cox regression analyses screened out three independent factors associated with worse prognosis: undifferentiated status, SWI/SNF complex deficiency, and lymph node metastasis. CONCLUSIONS: The SWI/SNF complex deficiency was more likely to result in a CSC phenotype and worse survival and was an independent prognostic factor in undifferentiated/dedifferentiated gastric carcinoma.

Superficial myofibroblastoma of the lower female genital tract: A clinicopathological analysis of 15 cases.

OBJECTIVE: To describe the clinicopathological features and differential diagnoses of 15 cases of superficial myofibroblastoma, a rare mesenchymal tumor involving the lower female genital tract. METHODS: The clinicopathological data and immunohistochemical findings were retrospectively analyzed in 15 cases of superficial myofibroblastoma. Meanwhile, a systematic literature review was conducted. RESULTS: The age of patients ranged from 34 to 73 years (median, 49 years). Most patients presented with nodular or polypoid masses ranging in size from 0.4 cm to 6.5 cm. Twelve tumors were located in the vagina, two in the vulva, and one in the cervix. Microscopically, the tumor was located in the subepithelial tissue, with a clear boundary and without capsule on the surface. The tumor cells were spindle, oval, stellate or wavy, and arranged in various architectural patterns of reticular, fascicular, wavy and disorderly patterns. There were no obvious cellular atypia and mitotic figures. Thin collagen fibers and thin-walled vessels could be observed in all cases. Most cases were diffusely and strongly reactive to Vimentin (12/12), Desmin (14/15), ER (15/15) and PR (13/14). Variable immunoreactivity for CD34 (8/15), Caldesmon (2/8), SMA (4/14) and CD99 (4/5) were observed. The tumors showed a low Ki67 proliferative index (≤5 %). Follow-up information was available in 10 patients and there was no evidence of recurrence or metastasis. CONCLUSIONS: Superficial myofibroblastoma is a rare benign tumor that originates from the hormone-sensitive, subepithelial mesenchymal tissue of the lower female genital tract, and should be differentiated from other mesenchymal tumors.

The immune function of heme oxygenase-1 from grass carp (Ctenopharyngodon idellus) in response to bacterial infection.

Heme oxygenase (HO)-1, a rate-limiting enzyme in heme catabolism, results in the formation of equivalent amounts of biliverdin (BV), carbon monoxide (CO) and ferrous iron (Fe2+). Previous studies have revealed that HO-1 plays an important role in immune responses. However, the mechanism underlying the immune responses against bacterial infection of teleost HO-1 remains enigmatic. To decipher the mechanisms, we have cloned and characterized the HO-1 gene of grass carp (designated as GcHO-1) in this research. The results showed that the open reading frame (ORF) of GcHO-1 was 819 bp, which encoded a putative protein of 272 amino acids. The deduced amino acid sequence phylogenetically shared the highest identity with other teleosts, and contained two domains of heme-oxygenase and a single-pass transmembrane domain. The mRNA expressions of GcHO-1 in healthy grass carp have widely existed in examined tissues in the following order of spleen > head-kidney > middle head-kidney > intestines > liver > gills > heart > muscle > brain. Besides, the mRNA and protein transcription of GcHO-1 were both significantly up-regulated in the liver and head-kidney tissues after Staphylococcus aureus and Aeromonas hydrophila infection. In addition, overexpression of GcHO-1 in kidney cell line (CIK) cells of grass carp could reduce the expression of inflammatory cytokines (IL-1ß, IL-8, TNFα, CCL1 and IL-6). Herein, we demonstrate that GcHO-1 plays an anti-inflammatory role in innate immunity. Our results shed new light on the mechanisms underlying the antibacterial immunity of teleost.

Clinical features of sarcomatoid change in patients with intrahepatic cholangiocarcinoma and prognosis after surgical liver resection: A Propensity Score Matching analysis.

BACKGROUND: Intrahepatic cholangiocarcinoma with sarcomatoid change (iCCA-SC) is a rare histological subtype of iCCA, the clinical features and outcomes after surgical resection on the prognosis is still unknown. METHODS: We retrospectively reviewed the clinical data of patients with histologically proven iCCA who underwent curative liver resection at our hospital between January 2008 and December 2018. Propensity score matching analysis was used to match patients with and without sarcomatoid change at a ratio of 1:4. The nomogram integrating all significant independent factors for overall survival (OS) and recurrence-free survival (RFS) was constructed to predict prognosis for iCCA. The predictive accuracy ability of the nomogram was determined by Harrell's index (C-index). RESULTS: A total of 40 iCCA-SC and 160 ordinary iCCA patients were included in this study. RFS and OS in the iCCA-SC group were significantly lower than those in the ordinary iCCA group (P<.001 and P = .002, respectively). The calibration curve for the probability of survival showed good agreement between the nomogram prediction and actual observation. CONCLUSION: The histological sarcomatoid subtype is an independent predictor of tumor recurrence and shorter OS in iCCA patients. The nomogram we established could provide more accurate prognostic prediction for iCCA patients.

Insight into the Regulatory Relationships between the Insulin-Like Androgenic Gland Hormone Gene and the Insulin-Like Androgenic Gland Hormone-binding Protein Gene in Giant Freshwater Prawns (Macrobrachium rosenbergii).

Giant freshwater prawns (Macrobrachium rosenbergii) are commonly found throughout the world. The size of the male giant freshwater prawn is much larger than that of the female. Therefore, understanding the molecular mechanism that underlies the sexual differentiation of M. rosenbergii is of both commercial and scientific importance. Insulin-like androgenic gland hormone (IAG) plays a key role in the differentiation of sex in M. rosenbergii. Although IAG has been investigated, the regulatory relationship between IAG and its binding protein partner, the insulin-like androgenic gland hormone-binding protein (IAGBP), has not been studied in M. rosenbergii. Here, we cloned and characterized the IAGBP from M. rosenbergii (Mr-IAGBP) for the very first time. Transcriptomic analysis showed that Mr-IAGBP mRNA was detected in a wide array of tissues with the highest expression found in the androgenic gland. The importance of IAG in male development was further demonstrated by an increase in IAG transcripts during the development of the androgenic gland and Mr-IAG was only highly transcribed in the androgenic gland of M. rosenbergii. Interestingly, we found that the Mr-IAG gene expression started during the 20th-day larva after hatching stage (LH20), followed (20th-day post-larval stage, PL20) by a gradual elevation of Mr-IAGBP levels. The levels of both genes peaked at the adult stage. The relationship between Mr-IAGBP and Mr-IAG was further analyzed using RNA interference. The injection of Mr-IAGBP double-stranded RNA (dsRNA) significantly reduced the transcription of Mr-IAG, while the amount of Mr-IAGBP mRNA and the translation of IAGBP protein was significantly reduced by the injection of Mr-IAG dsRNA. These results revealed that IAGBP is involved in IAG signaling. Furthermore, our data supports the hypothesis that (IAG and IAGBP)-IAG receptor signaling schemes exist in M. rosenbergii. Our results will provide important information for the further study of determining the sex of M. rosenbergii.

Matrilin-2 regulates proliferation, apoptosis and cell cycle during radiation-induced injury in HPAEpiC cell.

Radiation pulmonary injury is related to the accumulation of extracellular matrix proteins in the alveolar interstitial space. Matrilin-2 as a component of extracellular filamentous networks, present higher level in the lung tissue from irradiated mice and irradiated pulmonary epithelial cell line, HPAEpiC cells. Knockdown of endogenous matrilin-2 prevents the apoptosis of HPAEpiC cell induced by the irradiation injury. Consistently, over-expression of matrilin-2 reduced the proliferation and induced apoptosis of HPAEpiC cells. Matrilin-2 promotes the expression of p21 via increasing the transcriptional activity of p53, by which induces the G1 phase arresting in HPAEpiC cells. In summary, matrilin-2, increased by irradiation, reduced the proliferation and induces apoptosis of pulmonary epithelial cells via p53/p21 pathway.

High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-ß1).

This study aimed at evaluating the effect of high glucose on the expression of extracellular matrix (ECM) protein Matrilin-2 and the mechanism underlying this effect by using a mouse mesangial cell line. Mouse mesangial cells (MMCs) were cultured in media containing normal (5 mM d-glucose) or high concentrations of glucose (30 mM d-glucose). The expression of Matrilin-2 was assessed by either RT-PCR or western blot. Additionally, transforming growth factor beta 1 (TGF-ß1) inhibitors and TGF-ß1 were used to determine whether glucose-regulated Matrilin-2 expression was mediated by the TGF-ß1/Smad3 signaling pathway. Our data demonstrated that Matrilin-2 expression was markedly induced by high glucose and TGF-ß1. High glucose-induced Matrilin-2 expression was inhibited by TGF-ß1/Smad3 inhibitors, indicating that Matrilin-2 was markedly induced by high glucose and this induction was mediated by the TGF-ß1/Smad3 pathway. Taken together, our results showed that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-ß1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis and our finding provided a potential diagnostic and/or therapeutic target for DN.

Relationship between serum iron, zinc, calcium, and HIF-1a-comparative analysis of 2 regions and 4 ethnic groups in China.

Background: Altitude illness has serious effects on individuals who are not adequately acclimatized to high-altitude areas and may even lead to death. However, the individualized mechanisms of onset and preventive measures are not fully elucidated at present, especially the relationship between altitude illness and elements, which requires further in-depth research. Methods: Fresh serum samples were collected from individuals who underwent health examinations at the two hospitals in Xining and Sanya between November 2021 and December 2021. The blood zinc (Zn), iron (Fe), and calcium (Ca) concentrations, as well as hypoxia-inducible factor 1-alpha (HIF-1α) concentrations, were measured. This study conducted effective sample size estimation, repeated experiments, and used GraphPad Prism 9.0 and IBM SPSS version 19.0 software for comparative analysis of differences in the expression of elements and HIF-1α among different ethnic groups, altitudes, and concentration groups. Linear regression and multiple linear regression were employed to explore the relationships among elements and their correlation with HIF-1α. Results: This study included a total of 400 participants. The results from the repeated measurements indicated that the consistency of the laboratory test results was satisfactory. In terms of altitude differences, except for Fe (p = 0.767), which did not show significant variance between low and high altitude regions, Zn, Ca, and HIF-1α elements all exhibited notable differences between these areas (p < 0.0001, p = 0.004, and p < 0.0001). When grouping by the concentrations of elements and HIF-1α, the results revealed significant variations in the distribution of zinc among different levels of iron and HIF-1α (p < 0.05). The outcomes of the linear regression analysis demonstrated that calcium and zinc, iron and HIF-1α, calcium and HIF-1α, and zinc and HIF-1α displayed substantial overall explanatory power across different subgroups (p < 0.05). Finally, the results of the multiple linear regression analysis indicated that within the high-altitude population, the Li ethnic group in Sanya, and the Han ethnic group in Sanya, the multiple linear regression model with HIF-1αas the dependent variable and elements as the independent variables exhibited noteworthy overall explanatory power (p < 0.05). Conclusion: The levels of typical elements and HIF-1α in the blood differ among various altitudes and ethnic groups, and these distinctions may be linked to the occurrence and progression of high-altitude illness.

Establishment of cutoff values for anti-ß2 glycoprotein I antibodies in women of reproductive age in Southwest China.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-ß2 glycoprotein I (aß2GPI) antibodies and aimed to establish the first population-based cutoff values for aß2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-ß2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aß2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aß2GPI IgA, 27.54 RU/mL for aß2GPI IgM and 1.81 RU/mL for aß2GPI IgG, which indicated that the levels of aß2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aß2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aß2GPI IgA, 22.89% for aß2GPI IgG, and 9.64% for aß2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aß2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.

IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children.

Genetic factors play a crucial role in the immune response of juvenile idiopathic arthritis (JIA) and juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to investigate the association of IL12B (rs3212227, rs6887695) and IL17 (rs2275913, rs763780) gene polymorphisms with the susceptibility of JIA and JSLE in Chinese children. A total of 303 healthy controls and 304 patients including 160 JIA and 144 patients were analyzed, and the genetic polymorphisms were genotyped by using a Sequenom MassArray system. There was a significant association between the IL12B rs3212227 genotype and the increased risk of JSLE (P = .01). For rs6887695, the minor allele C was significantly associated with the increased risk of JIA (odds ratio = 1.48, 95% confidence interval [CI] = 1.12-1.95, P = .005). Moreover, rs6887695 genotype was significantly associated with both JIA and JSLE susceptibility (P < .05). Besides, IL12B haplotype GC significantly associated with the increased risk of JIA (P = .016). However, no significant difference was found between the IL17 (rs2275913, rs763780) gene polymorphisms and JIA or JSLE susceptibility (P > .05). And similar genotype distributions of IL12B and IL17 polymorphisms were found between the patients with nephritis and without nephritis in JSLE (P > .05). Our results indicated that IL12B polymorphisms was associated with an increased risk for the development of JIA and JSLE in Chinese children, highlighting the involvement of inflammation in the pathogenesis of JIA and JSLE. Moreover, there was a risk haplotype in IL12B which could increase the risk of JIA.

Can acute high-altitude sickness be predicted in advance?

In high-altitude environments, the oxygen and air density are decreased, and the temperature and humidity are low. When individuals enter high-altitude areas, they are prone to suffering from acute mountain sickness (AMS) because they cannot tolerate hypoxia. Headache, fatigue, dizziness, and gastrointestinal reactions are the main symptoms of AMS. When these symptoms cannot be effectively alleviated, they can progress to life-threatening high-altitude pulmonary edema or high-altitude cerebral edema. If the risk of AMS can be effectively assessed before people enter high-altitude areas, then the high-risk population can be promptly discouraged from entering the area, or drug intervention can be established in advance to prevent AMS occurrence and avoid serious outcomes. This article reviews recent studies related to the early-warning biological indicators of AMS to provide a new perspective on the prevention of AMS.

Hemeprotein amplifies the innate immune receptors of Ctenopharyngodon idellus kidney cells through NF-κB- and MAPK-dependent reactive oxygen species generation.

Infectious bacterial and viral diseases that cause hemolysis are considered life-threatening to grass carp (Ctenopharyngodon idellus), which is a species used in aquaculture worldwide. After heme and hemeproteins (Hb) are released as a result of hemolysis, the effect of excess Hb and heme on tissues remains to be characterized. To decipher the mechanisms, after incubation with Hb, we showed that lipopolysaccharide (LPS), Hb, and heme increased the cytotoxicity and secretion of inflammatory cytokines such as interleukin (IL)-6, chemokine (C-C motif) ligand 1 (CCL1), tumor necrosis factor (TNF)-α, IL-6, and IL-1ß in vitro, which was due to stimulation of the expression of innate immune receptors, such as nucleotide-binding oligomerization domain (NOD2), toll-like receptor 2 (TLR2), TLR 4, and TLR3. The formation of reactive oxygen species (ROS) and the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB were important for increasing the cytokine production to induce heme, Hb, and LPS. Moreover, we confirmed that after LPS, Hb, and heme challenge, superoxide dismutase (SOD) and glutathione (GSH) synthetase (GSS) also caused remarkable destruction. However, catalase (CAT) and heme oxygenase-1 (HO-1) were strongly activated. In summary, our research findings present a framework through which heme and Hb concentrations amplify the secretions of inflammatory cytokines, which are induced by pattern recognition receptor (PRR) activation and present possible paths for immune intervention during infection with viral diseases and hemolytic bacterial.

Malignant Transformation in Vestibular Schwannoma: Clinical Study With Survival Analysis.

AIM: Vestibular schwannomas (VSs) are generally considered benign tumors, and malignant transformation of VSs (MTVSs) are rare findings. The clinical features, treatment strategy, outcomes and prognostic factors remain unclear. We endeavored to analyze the natural history, management, outcomes and prognostic factors of MTVSs. MATERIALS AND METHODS: The clinical features, radiologic findings, pathological investigations and surgical outcomes of 4 patients with MTVSs treated at the authors' institution between 2010 and 2019 were retrospectively collected. Related literature published until December 2019 (63 articles, 67 patients) was evaluated. The authors also made a pooled analysis to evaluate the risk factors for overall survival (OS) time. RESULTS: Of the 4 cases in our series, 3 cases were malignant transformation following previous treatment (surgery and radiosurgery) and 1 was primary MTVS. Of the 71 MTVSs from the literature, 27 were male and 39 were female, with the mean age of 47.2 ± 17.5 years old. Twelve patients (18.5%) were diagnosed with NF2 (15.4%) or NF1 (3.1%). Forty-three (61.4%) patients underwent previous treatment (surgery and/or radiotherapy) prior to the pathological diagnosis of MTVSs. The mean size of the MTVSs was 35.1 ± 13.2mm. The mean Ki-67 index was 30.6% ± 18.8%. Twenty-four (49.0%) patients underwent gross total resection, 25 (51.0%) patients underwent incomplete resection. Twenty-five (44.6%) underwent adjuvant radiotherapy (RT) postoperatively. During the average follow-up of 9.9 ± 9.5 months (range, 0-40 months), 37 (82.2%) patients developed a local recurrence or metastasis. Forty-seven (73.4%) patients died of tumor progression or postoperative complications. The overall 1-year and 2-year survival rate was 42.3% and 18.6% respectively. Log-rank testing for Kaplan-Meier survival analysis identified that size (P = 0.047) and adjuvant radiotherapy (P=0.001) were significant prognostic factors for OS. Multivariate analysis revealed that adjuvant RT was the only prognostic factor for longer OS (P = 0.005). CONCLUSIONS: MTVSs are rare, fatal disease, prone to recur and metastasize rapidly, resulting in death in most of the cases. We found that GTR did not improve the survival in MTVSs but postoperative adjuvant RT can significantly improve the OS, and we recommend early postoperative RT in MTVSs regardless of extent of resection.

Expression and functional analysis of the BCL2-Associated agonist of cell death (BAD) gene in grass carp (Ctenopharyngodon idella) during bacterial infection.

The BCL2-associated agonist of cell death protein is a key participant in apoptosis dependent on mitochondria and in disease progression that involves the regulation of cell death, such as tumorigenesis, diabetes, sepsis shock, and epilepsy. Nevertheless, the mechanisms underlying the immune responses to teleost BAD bacterial infection and mitochondrial-dependent apoptosis remains unclear. In order to elucidate the mechanisms involved, in this study, a Ctenopharyngodon idella (grass carp) BAD gene named GcBAD1 was firstly cloned and characterized. The results indicated that the ORF (open reading frame) of GcBAD1 was 438 bp in length, encoding a 145-amino acid putative protein of 16.66 kDa. This deduced amino acid sequence has a better identity than another teleost species according to a phylogenetic analysis, and contains a Bcl2-BAD-1 domain. In healthy grass carp fish, the mRNA transcripts of GcBAD1 were widely present in the studied tissues, which could be ranked as follows; spleen > brain > middle-kidney > head-kidney > liver > gills > intestines > heart and muscle. In addition, during infection by Aeromonas hydrophila and Staphylococcus aureus, the mRNA transcription and protein levels expression of GcBAD1 in the head-kidney, spleen, and liver tissues of the fish were significantly up-regulated. Moreover, when the C. idellus kidney cell line (CIK) cells were incubated with Lipopolysaccharide (LPS) and lipoteichoic acid (LTA), the GcBAD1 expression transcripts were also significantly up-regulated. Additionally, overexpression of GcBAD1 in CIK cells was able to activate apoptosis-related genes, including those encoding p53, Cytochrome C (CytoC), caspase-3, and caspase-9. Besides, in the TUNEL assays, when pEGFP-BAD1 was over-expressed, the number of red signals associated with apoptosis were significantly increased in the CIK cells infected with LPS or LTA at 12 h. This study demonstrates that GcBAD1 has a significant role in the mitochondrial apoptosis pathway of grass carp's innate immunity. Our findings provide new insight into the potential mechanisms of teleost antibacterial immunity.

A high-quality genome assembly highlights rye genomic characteristics and agronomically important genes.

Rye is a valuable food and forage crop, an important genetic resource for wheat and triticale improvement and an indispensable material for efficient comparative genomic studies in grasses. Here, we sequenced the genome of Weining rye, an elite Chinese rye variety. The assembled contigs (7.74 Gb) accounted for 98.47% of the estimated genome size (7.86 Gb), with 93.67% of the contigs (7.25 Gb) assigned to seven chromosomes. Repetitive elements constituted 90.31% of the assembled genome. Compared to previously sequenced Triticeae genomes, Daniela, Sumaya and Sumana retrotransposons showed strong expansion in rye. Further analyses of the Weining assembly shed new light on genome-wide gene duplications and their impact on starch biosynthesis genes, physical organization of complex prolamin loci, gene expression features underlying early heading trait and putative domestication-associated chromosomal regions and loci in rye. This genome sequence promises to accelerate genomic and breeding studies in rye and related cereal crops.

PITPNC1 fuels radioresistance of rectal cancer by inhibiting reactive oxygen species production.

BACKGROUND: Neoadjuvant radiotherapy is a commonly used method for the current standard-of-care for most patients with rectal cancer, when the effects of radioresistance are limited. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1), a lipid-metabolism-related gene, has previously been proved to manifest pro-cancer effects in multiple types of cancer. However, whether PITPNC1 plays a role for developing radioresistance in rectal cancer patients is still unknown. Therefore, this study aims to investigate the role of PITPNC1 in rectal cancer radioresistance. METHODS: Patient-derived tissue were used to detect the difference in the expression level of PITPNC1 between radioresistant and radiosensitive patients. Bioinformatic analyses of high-throughput gene expression data were applied to uncover the correlations between PITPNC1 level and oxidative stress. Two rectal cancer cell lines, SW620, and HCT116, were selected in vitro to investigate the effect of PITPNC1 on radioresistance, reactive oxygen species (ROS) generation, apoptosis, and proliferation in rectal cancer. RESULTS: PITPNC1 is highly expressed in radioresistant patient-derived rectal cancer tissues compared to radiosensitive tissue; therefore, PITPNC1 inhibits the generation of ROS and improves the extent of radioresistance of rectal cancer cell lines and then inhibits apoptosis. Knocking down PITPNC1 facilitates the production of ROS while application of the ROS scavenger, N-acetyl-L-cysteine (NAC), could reverse this effect. CONCLUSIONS: PITPNC1 fuels radioresistance of rectal cancer via the inhibition of ROS generation.