[Application of Preschool Auditory Processing Assessment Scale in children with attention deficit hyperactivity disorder]. / å­¦é¾„å‰å„¿ç«¥å¬å¤„ç†è¯„ä¼°é‡è¡¨åœ¨æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å„¿ç«¥ä¸­çš„åº”ç”¨ç ”ç©¶.

OBJECTIVES: To investigate the characteristics of auditory processing (AP) in preschool children with attention deficit hyperactivity disorder (ADHD) using Preschool Auditory Processing Assessment Scale (hereafter referred to as "auditory processing scale"). METHODS: A total of 41 children with ADHD and 41 typically developing (TD) children were assessed using the auditory processing scale, SNAP-IV rating scale, and Conners' Kiddie Continuous Performance Test (K-CPT). The auditory processing scale score was compared between the TD and ADHD groups. The correlations of the score with SNAP-IV and K-CPT scores were assessed. RESULTS: Compared with the TD group, the ADHD group had significantly higher total score of the auditory processing scale and scores of all dimensions except visual attention (P<0.05). In the children with ADHD, the attention deficit dimension score of the SNAP-IV rating scale was positively correlated with the total score of the auditory processing scale (rs30=0.531, P<0.05; rs27=0.627, P<0.05) as well as the scores of its subdimensions, including auditory decoding (rs=0.628, P<0.05), auditory attention (rs=0.492, P<0.05), and communication (rs=0.399, P<0.05). The hyperactivity-impulsivity dimension score of the SNAP-IV rating scale was positively correlated with the hyperactivity-impulsivity dimension score of the auditory processing scale (rs=0.429, P<0.05). In the children with ADHD, the attention deficit dimension score of the K-CPT was positively correlated with the total score (rs30=0.574, P<0.05; rs27=0.485, P<0.05) and the hyperactivity-impulsivity dimension score (rs=0.602, P<0.05) of the auditory processing scale. CONCLUSIONS: Preschool children with ADHD have the risk of AP abnormalities, and the auditory processing scale should be used early for the screening and evaluation of AP abnormalities in children.

Assessment of SENP3-interacting proteins in hepatocytes treated with diethylnitrosamine by BioID assay.

SUMOylation of proteins regulates cell behaviors and is reversibly removed by small ubiquitin-like modifier (SUMO)-specific proteases (SENPs). The SENP family member SENP3 is involved in SUMO2/3 deconjugation and has been reported to sense cell stress and accumulate in several human cancer cells and macrophages. We previously reported that Senp3-knockout heterozygous mice showed smaller liver, but the pertinent mechanisms of SENP3 and SUMOylated substrates remain unclear. Thus, in this study, we investigated the interacting proteins with SENP3 and the alteration in hepatocytes treated with the xenobiotic diethylnitrosamine (DEN), which is specifically transformed in the liver and induces DNA double-strand breaks. Our data revealed that a certain amount of SENP3 was present in normal, untreated hepatocytes; however, DEN treatment promoted rapid SENP3 accumulation. SENP3 was mainly localized in the nuclei, and its level was significantly increased in the cytoplasm after 2 h of DEN treatment. The application of the recent proximity-dependent biotinylation (BioID) method led to the identification of 310 SENP3-interacting proteins that were involved in not only gene transcription but also RNA splicing, protein folding, and metabolism. Furthermore, after DEN exposure for a short duration, ribosomal proteins as well as proteins associated with mitochondrial ATP synthesis, membrane transport, and bile acid synthesis, rather than DNA repair proteins, were identified. This study provides insights into the diverse regulatory roles of SENP3, and the BioID method seems to be efficient for identifying physiologically relevant insoluble proteins.

Tumor suppressor HIC1 is synergistically compromised by cancer-associated fibroblasts and tumor cells through the IL-6/pSTAT3 axis in breast cancer.

BACKGROUND: Interleukin-6 (IL-6) is commonly highly secreted in the breast cancer (BrCA) microenvironment and implicated in disease development. In this study, we aimed to determine the role of the IL-6/pSTAT3/HIC1 axis in the breast cancer microenvironment, including in cancer-associated fibroblasts (CAFs) and breast cancer cells. METHODS: Stromal fibroblasts from the breast cancer tissue were isolated, and the supernatants of the fibroblasts were analyzed. Recombinant human IL-6 (rhIL-6) was applied to simulate the effect of CAF-derived IL-6 to study the mechanism of HIC1 (tumor suppressor hypermethylated in cancer 1) downregulation. IL-6 was knocked down in the high IL-6-expressing BrCA cell line MDA-MB-231, which enabled the investigation of the IL-6/pSTAT3/HIC1 axis in the autocrine pathway. RESULTS: Increased IL-6 was found in the supernatant of isolated CAFs, which suppressed HIC1 expression in cancer cells and promoted BrCA cell proliferation. After stimulating the BrCA cell line SK-BR-3 (where IL-6R is highly expressed) with rhIL-6, signal transducers and activators of transcription 3 (STAT3) was found to be phosphorylated and HIC1 decreased, and a STAT3 inhibitor completely rescued HIC1 expression. Moreover, HIC1 was restored upon knocking down IL-6 expression in MDA-MB-231 cells, accompanied by a decrease in STAT3 activity. CONCLUSIONS: These findings indicate that IL-6 downregulates the tumor suppressor HIC1 and promotes BrCA development in the tumor microenvironment through paracrine or autocrine signaling.

Chronic inflammatory pain upregulates expression of P2Y2 receptor in small-diameter sensory neurons.

Roles of ionotropic purinergic (P2X) receptors in chronic pain have been intensively investigated. However, the contribution of metabotropic purinergic (P2Y) receptors to pathological pain is controversial. In the present study, using single cell RT-PCR (reverse transcription-polymerase chain reaction) and single cell nested-PCR techniques, we examined the expression of P2X(2), P2X(3), P2Y(1) and P2Y(2) mRNA transcripts in retrogradely labeled cutaneous sensory neurons from mouse lumber dorsal root ganglia (DRGs) following peripheral inflammation. The percentage of cutaneous sensory neurons expressing P2Y(2) mRNA transcripts increased after complete Freund's adjuvant (CFA) treatment. Particularly, the P2Y(2) mRNA transcripts were more frequently detected in small-diameter cutaneous neurons from CFA-treated mice than those from control mice. Coexpression of P2Y(2) and P2X (P2X(2) or P2X(3)) mRNAs was more frequently observed in cutaneous sensory neurons from CFA-treated mice relative to controls. Pain behavioral tests showed that the blockade of P2Y receptors by suramin attenuated mechanical allodynia evoked either by CFA or uridine triphosphate (UTP), an endogenous P2Y(2) and P2Y(4) agonist. These results suggest that chronic inflammatory pain enhances expression of P2Y(2) receptor in peripheral sensory neurons that innervate the injured tissue and the activation of P2Y receptors contributes to mechanical allodynia following inflammation.

Comprehensive analysis of WOX transcription factors provide insight into genes related to the regulation of unisexual flowers development in Akebia trifoliata.

Akebia trifoliata is a fascinating economic and medicinal plant that produces functionally unisexual flowers due to stamen/pistil abortion during flower development, and the genetic regulation pathway of this process remain completely unknown. Here, 10 AktWOXs were identified for the first time, all contained a highly conserved homeodomain. AktWOXs were divided into three clades, each with the same or similar intron, exon, and motifs distribution. Many cis-elements related to stress response, growth and development, and hormone response were found in the AktWOXs promoter region. In addition, four candidate genes AktWOX8, AktWOX11, AktWOX13.2 and AktWUS that might be involved in unisexual flowers development were screened, all of which were located in the nucleus and showed transcriptional activation activity. Yeast one-hybrid showed that both AktKNU and AktAG1, the potential core transcription factors in the activity termination pathway of flower meristem stem cells, could bind to the promoter region of AktWUS. Dual-luciferase assay further confirmed that only AktKNU inhibited the expression of AktWUS. Collectively, this study revealed the mechanism of AktWUS that might affect the formation of unisexual flowers by regulating the timely termination of flower meristem in A. trifoliata.

Effect of hypoxia­HIF­1α­periostin axis in thyroid cancer.

The incidence of thyroid carcinoma (TC) has exhibited a rapid increase in recent years. A proportion of TCs exhibit aggressive behavior. The present study aimed to investigate the potential role of hypoxia­hypoxia inducible factor 1 subunit α (HIF­1α)­periostin axis in the progression of TC. The upregulation of periostin and HIF­1α expression levels was detected in 95 clinical TC tissues as compared with normal thyroid tissues. Hypoxia promoted the viability and invasion of TC cells and this effect was inhibited by the downregulation of periostin. Hypoxia also induced the Warburg effect in TC and this effect was inhibited by the silencing of periostin. Further investigations revealed that hypoxia activated HIF­1α, which in turn regulated the expression of periostin. Immunoprecipitation and dual luciferase reporter assays demonstrated that HIF­1α upregulated the expression of periostin by binding to the promoter of periostin. On the whole, these findings suggest the existence of a hypoxia­HIF­1α­periostin axis in TC and indicate the role of this axis in the progression of TC.

Characteristics of Speech Auditory Brainstem Response in Preschool Children With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: This study aimed to investigate the characteristics of auditory processing (AP) in preschool children with attention-deficit/hyperactivity disorder (ADHD) using the speech auditory brainstem response (speech-ABR), which provides insights into the AP of speech signals in the central auditory nervous system (CANS). METHOD: A total of 84 preschool children diagnosed with ADHD, aged 4-6 years, were matched with 84 typically developing (TD) children based on gender and age. All children underwent speech-ABR testing, cognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition or the Wechsler Intelligence Scale for Children-Fourth Edition, and a continuous performance test. RESULTS: Children with ADHD exhibited significantly longer latencies of speech-ABR waveforms V, A, and D compared to TD children. Multiple linear regression analysis showed that the latencies of speech-ABR waves V, A, and D were affected by the presence of ADHD, but not by the full-scale intelligence quotient. CONCLUSIONS: This study revealed that preschool children with ADHD exhibited abnormal AP of speech signals in their CANS. The findings suggest that speech-ABR can be utilized as a reliable measure to evaluate AP ability in this population, as it remains unaffected by cognitive or attentional factors. The transient response (V, A) of speech-ABR was found to be a significant predictor of ADHD in a clinical setting. Early assessment of AP abnormalities via speech-ABR is recommended in preschool-age children to develop targeted interventions for ADHD. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26376502.

Sensitive electrochemical biosensor for rapid detection of sEV-miRNA based turbo-like localized catalytic hairpin assembly.

Small extracellular vesicle-associated microRNAs (sEV-miRNAs) have emerged as critical biomarkers for cancer diagnosis, yet the rapid detection of these low-abundance molecules in clinical samples remains a formidable challenge. Herein, a simple turbo-like localized catalytic hairpin assembly (TL-CHA) was proposed for sEV-miR-1246 measurement. This electrochemical sensor achieves dual localization through the ingeniously use of AuNPs and DNA nanowires, which provides rich sites for CHA cascade amplification, significantly enhancing the effective reaction and amplify the detection response. Leveraging this innovative design, this biosensor demonstrated the ability to detect sEV-miRNA at concentrations as low as 5.24 aM in a time frame of 30 min. The precision of the measurements was validated through reverse transcription quantitative polymerase chain reaction. Furthermore, the sensor was used for analyzing plasma samples from gastric cancer patients yielded AUC values of 0.973 for all stages and 0.945 for early stages. This demonstrates the sensor's robust performance in both the staging diagnosis and early screening of gastric cancer. Therefore, this platform has great potential for the clinical cancer diagnosis.

Deciphering the regulatory mechanisms and biological implications of ARID1A missense mutations in cancer.

ARID1A is a key component of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex and functions as a critical tumor suppressor in various cancers. In this study, we find that tumor cells with hotspot missense mutations in ARID1A (AT-rich interactive domain-containing protein 1A) exhibit a malignant phenotype. Mechanistically, these mutations facilitate the translocation of ARID1A mutant proteins to the cytoplasm by the nucleocytoplasmic shuttler XPO1 (exportin 1). Subsequently, the E3 ubiquitin ligase STUB1 ubiquitinates the ARID1A mutant protein, marking it for degradation. Knocking down STUB1 or inhibiting XPO1 stabilizes the ARID1A mutant protein, retaining it in the nucleus, which restores the assembly of the cBAF complex, the chromatin remodeling function, and the normal expression of genes related to the MAPK and anti-apoptotic pathways, thereby decreasing the tumor burden. Our research shows that nuclear-localized mutated ARID1A proteins retain tumor-suppressive function. We identify promising strategies to treat cancers harboring missense mutations in the BAF complex.

Features of Cognitive Ability and Central Auditory Processing of Preschool Children With Minimal and Mild Hearing Loss.

OBJECTIVE: This study aimed to investigate the current status of cognitive development and central auditory processing development of preschool children with minimal and mild hearing loss (MMHL) in Nanjing, China. METHOD: We recruited 34 children with MMHL and 45 children with normal hearing (NH). They completed a series of tests, including cognitive tests (i.e., Wechsler Preschool and Primary Scale of Intelligence and Continuous Performance Test), behavioral auditory tests (speech-in-noise [SIN] test and frequency pattern test), and objective electrophysiological audiometry (speech-evoked auditory brainstem response and cortical auditory evoked potential). In addition, teacher evaluations and demographic information and questionnaires completed by parents were collected. RESULTS: Regarding cognitive ability, statistical differences in the verbal comprehensive index, full-scale intelligence quotient, and abnormal rate of attention test score were found between the MMHL group and the NH group. The children with MMHL performed poorer on the SIN test than the children with NH. As for the auditory electrophysiology of the two groups, the latency and amplitude of some waves of the speech-evoked auditory brainstem response and cortical auditory evoked potential were statistically different between the two groups. We attempted to explore the relationship between some key indicators of auditory processing and some key indicators of cognitive development. CONCLUSIONS: Children with MMHL are already at increased developmental risk as early as preschool. They are more likely to have problems with attention and verbal comprehension than children with NH. This condition is not compensated with increasing age during the preschool years. The results suggest a possible relationship between the risk of cognitive deficit and divergence of auditory processing. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22670473.

Does Green Governance Efficiency and Green Finance Polices Matters in Sustainable Environment: Implications for Public Health.

Rapid and widespread changes in the environment and climate, such as rising temperatures, water and air pollution, floods, and droughts, disease vector migration are putting human health at risk. In this case, green governance is an essential driver for the restructuring of economic development and realizing a green technological revolution for sustainable development and its implications for public health. This article aims to explore the effects and interrelationships of green governance and green finance policies on sustainable development in various regions of China's from 2008 to 2018 using panel data estimation technique. The findings show that China's overall green governance index and green finance policies resulted in a substantial decrease in environmental pollution during the study time. Financial inclusion also be a factor to the reduction of CO2 emissions and has a positive influence on environmental security investment projects, according to our findings. China is on track to become a world leader in an enactment of green finance concept, and controllers must speed up the development of green finance products and strengthen financial institutions' ability to provide green credit. Policymakers should promote green governance and green fiancé to keenly play a part in environmental security projects that boost green spending while minimizing the procedural risk.

The Influence of Media Diversification Model and Entrepreneurship on Enterprise Financial Performance Under the Environment of Sustainable Development.

Market competition is intensifying. The necessity and path of adopting the diversified management model in the media industry are explored to delve into the influence of the media diversification model and entrepreneurship on enterprise financial performance. Besides, the relevant theories such as the media diversification model and entrepreneurial spirit are expounded. Furthermore, Time Publishing & Media is taken as the representative of the media diversification model. Finally, the influence of entrepreneurship on financial performance is discussed regarding entrepreneurship in the Yangtze River Delta as the research object. The profitability, solvency, and operation ability of Time Publishing & Media are analyzed. It is found that there are problems in the profitability and operation ability of Time Publishing & Media. The solvency is good, and the risk of debt repayment is low. As a result, a diversified management model may not have a positive impact on enterprise performance. In addition, the entrepreneurial spirit of the Yangtze River Delta is studied, and the results reveal that the F values from 2017 to 2019 are about 66.24, 10.78, and 60.39, respectively, with a significance of 0.00. It implies that the stronger the entrepreneur's ability to take risks, the better the financial performance of the enterprise, but the risk should be appropriate. Therefore, the research on the influence of the media diversification model and entrepreneurship on the financial performance of enterprises in the environment of sustainable development has guided significance for enterprises to improve their business performance and market competitiveness.

Meta-Analysis of the Effect of Nursing Intervention on Children with Type 2 Diabetes.

Objective: To systematically evaluate the effect of nursing intervention on children with type 2 diabetes. Methods: The randomized controlled trials (RCTs) on nursing intervention in children with type 2 diabetes in CNKI, VIP, WanFang, Chinese Biomedical Database (CBM), PubMed, The Cochrane Library, Embase, and Science were searched by the computer until July 2022. Two evaluators reviewed the articles, selected the information, and assessed their quality according to the inclusion criteria and exclusion criteria and then carried out meta-analysis with RevMan 5.3. Results: A total of 5 RCT studies were kept, including 319 patients with type 2 diabetes (≤21 years old), where 162 patients were in the nursing group and 157 patients were in the control group. Meta-analysis revealed that, compared with routine nursing, nursing intervention could effectively control children's fasting blood glucose (FBG) (MD = -1.68, 95% CI (-2.19, -1.17), P < 0.00001), 2 h postprandial blood glucose (2hPG) (MD = -4.01, 95% CI (-4.70, -3.33), P < 0.00001), fasting insulin (FINS) (MD = -7.42, 95% CI (-10.63, -4.20), P < 0.00001), 2 h postprandial insulin (2hINS) (MD = -58.18, 95% CI (-103.24, -13.11), P = 0.01), triglycerides (TG) (MD = -0.41, 95% CI (-0.56, -0.25), P < 0.00001), and systolic blood pressure (SBP) (MD = -8.85, 95% CI (-14.67, -3.03), P = 0.003) and effectively maintain patients' blood glucose at a normal level (MD = -8.85, 95% CI (-14.67, -3.03), P = 0.003), where all the differences were statistically significant. Conclusion: The existing evidence showed that nursing intervention has a significant effect in controlling normal blood glucose and improving insulin utilization in children with type 2 diabetes, which can effectively improve the therapeutic effect on children.

Nano-sulfur confined in a 3D carbon nanotube/graphene network as a free-standing cathode for high-performance Li-S batteries.

A free-standing nano-sulfur-based carbon nanotube/graphene (S/CNT/G) film with a conductive interlinked three-dimensional (3D) nanoarchitecture is fabricated via a facile solution-based method. This 3D multidimensional carbon-sulfur network combines three different nanoarchitectures, as follows: zero-dimensional sulfur nanoparticles, one-dimensional carbon nanotubes, and two-dimensional graphene. The CNTs with a one-dimensional structure act as a conductive matrix, and graphene with two-dimensional sheets is intercalated into the CNT scaffold to build a 3D structure, extending in an additional dimension to provide improved restriction for sulfur/polysulfides. Zero-dimensional sulfur nanoparticles are anchored uniformly on the interpenetrative 3D carbon framework to form a free-standing cathode. Moreover, this well-designed S/CNT/G film is flexible, highly conductive, binder free and current collector free. When directly used as a flexible cathode electrode, the synthesized S/CNT/G film delivers both excellent long-term cycling and high-rate performances. A high initial capacity of 948 mA h g-1 is obtained, and subsequently, a reversible discharge capacity of 593 mA h g-1 over 200 cycles is achieved at 0.5C. Even at a high rate of 3C, the S/CNT/G film with a 50 wt% sulfur content still exhibits a discharge capacity of 598 mA h g-1. These results demonstrate the great potential of the S/CNT/G nanocomposite as a flexible and binder-free cathode for high performance Li-S batteries.

The development, validity, reliability, and norm of a preschool auditory processing assessment scale in China.

BACKGROUND: Children with auditory processing deficits may face problems with language, learning, and social communication. AIMS: To develop a Chinese auditory processing assessment scale for preschool children and establish the norms of the scale. METHODS AND PROCEDURES: The predictive version of the scale was formed by a literature review, qualitative interviews, expert consultation, and a pre-test with a small sample. Nine kindergartens in Nanjing were selected by a stratified cluster sampling plan. First, 734 children from two kindergartens were selected for the large sample pre-test of the scale. Then, 1526 children from four kindergartens and 1151 children from three kindergartens were selected for the reliability and validity analysis and confirmatory factor analysis, respectively. The standardized norm data of the scale were established based on the 3411 points of scale data of the nine kindergartens. Finally, the clinical usefulness of the scale was analyzed by comparing the results of objective auditory processing tests in children with normal and abnormal auditory processing prompted by the score on the scale. OUTCOMES AND RESULTS: The preschool auditory processing assessment scale includes 5 dimensions and 30 items. The Cronbach's alpha value of the scale is greater than 0.9. The confirmatory factor analysis results verify that the scale structure is reasonable. The percentile norm of the scale was established. The results of electrophysiological tests of the normal and abnormal auditory processing groups were statistically different (P < 0.05). CONCLUSIONS AND IMPLICATIONS: The developed preschool auditory processing assessment scale has good reliability and validity. The scale is suitable for clinical application.

Vaccination with Omicron Inactivated Vaccine in Pre-vaccinated Mice Protects against SARS-CoV-2 Prototype and Omicron Variants.

In response to the fast-waning immune response and the great threat of the Omicron variant of concern (VOC) to the public, we report the pilot-scale production of an inactivated Omicron vaccine candidate that induces high levels of neutralizing antibody titers to protect against the Omicron virus. Here, we demonstrate that the inactivated Omicron vaccine is safe and effective in recalling immune responses to the HB02, Omicron, and Delta viruses after one or two doses of BBIBP-CorV. In addition, the efficient productivity and good genetic stability of the manufactured inactivated vaccine is proved. These results support the further evaluation of the Omicron vaccine in a clinical trial.

Electrophysiological Screening for Children With Suspected Auditory Processing Disorder: A Systematic Review.

Objective: This research aimed to provide evidence for the early identification and intervention of children at risk for auditory processing disorder (APD). Electrophysiological studies on children with suspected APDs were systematically reviewed to understand the different electrophysiological characteristics of children with suspected APDs. Methods: Computerized databases such as PubMed, Cochrane, MEDLINE, Web of Science, and EMBASE were searched for retrieval of articles since the establishment of the database through May 18, 2020. Cohort, case-control, and cross-sectional studies that evaluated the literature for the electrophysiological assessment of children with suspected APD were independently reviewed by two researchers for literature screening, literature quality assessment, and data extraction. The Newcastle-Ottawa Scale and 11 entries recommended by the Agency for Healthcare Research and Quality were used to evaluate the quality of the literature. Results: In accordance with the inclusion criteria, 14 articles were included. These articles involved 7 electrophysiological testing techniques: click-evoked auditory brainstem responses, frequency-following responses, the binaural interaction component of the auditory brainstem responses, the middle-latency response, cortical auditory evoked potential, mismatch negativity, and P300. The literature quality was considered moderate. Conclusions: Auditory electrophysiological testing can be used for the characteristic identification of children with suspected APD; however, the value of various electrophysiological testing methods for screening children with suspected APD requires further study.

Hyperprolactinemia due to pituitary metastasis: A case report.

BACKGROUND: Pituitary metastasis is an uncommon manifestation of systemic malignant tumors. Moreover, hyperprolactinemia and overall hypopituitarism caused by metastatic spread leading to the initial symptoms are rare. CASE SUMMARY: A 53-year-old male patient was admitted to our hospital with complaints of bilateral blurred vision, dizziness, polyuria, nocturia, severe fatigue and somnolence, decreased libido, and intermittent nausea and vomiting for more than 6 mo. During the last 7 d, the dizziness had worsened. Laboratory investigations revealed overall hypofunction of the pituitary gland, but the patient had an elevated serum prolactin level (703.35 mg/mL). Preoperative magnetic resonance imaging revealed a tumor in the sellar region, accompanied by intratumoral hemorrhage and calcification. Thus, transnasal subtotal resection of the lesion in the sellar region was performed. The histopathological and immunohistochemical examinations of the resected lesion revealed metastasis of lung adenocarcinoma to the pituitary gland. Oral hydrocortisone (30 mg/d) and levothyroxine (25 mg/d) were given both pre- and postoperatively. Post-operatively, the clinical symptoms were significantly improved. However, 4 mo following the surgery, the patient succumbed due to multiple organ failure. CONCLUSION: Hyperprolactinemia is one of the markers of poor prognosis in patients with carcinoma that metastasizes to the pituitary gland. Exogenous hormone supplementation plays a positive role in relieving the symptoms of patients and improving quality of life.

Molecular evolution of the MLO gene family in Oryza sativa and their functional divergence.

The present study identified 12 MLO genes in rice that were located on chromosomes 1, 2, 3, 4, 5, 6, 10, and 11 respectively without any obvious clustering. On a genome scale we showed that the expansion of rice MLO gene family was primarily attributed to segmental duplication produced by polyploidy, rather than through tandem amplification. Gene conversion events should also play important roles in the evolution of MLO genes. The results of relative rate ratio test and maximum likelihood analysis suggested that positive selection should have occurred after gene duplication and/or speciation, prompting the formation of distinct MLO subfamilies. Functional divergence analysis provided statistical evidence for shifted evolutionary rate after gene duplication. Compared to extracellular loop 3 and Ca(2+)-binding domain, much stronger functional constraints should impose on intracellular loop 2, although all of the three regions might be under purifying selection. The sliding window analysis of d(N)/d(S) ratio values identified one sequence region where strong functional constraints must impose on, and consequently should be crucial for functionality of MLO genes.