The OsMOB1A-OsSTK38 kinase complex phosphorylates CYCLIN C, controlling grain size and weight in rice.

Grain size and weight are crucial yield-related traits in rice (Oryza sativa). Although certain key genes associated with rice grain size and weight have been successfully cloned, the molecular mechanisms underlying grain size and weight regulation remain elusive. Here, we identified a molecular pathway regulating grain size and weight in rice involving the MPS ONE BINDER KINASE ACTIVATOR-LIKE 1A-SERINE/THREONINE-PROTEIN KINASE 38-CYCLIN C (OsMOB1A-OsSTK38-OsCycC) module. OsSTK38 is a nuclear Dbf2-related kinase that positively regulates grain size and weight by coordinating cell proliferation and expansion in the spikelet hull. OsMOB1A interacts with and enhances the autophosphorylation of OsSTK38. Specifically, the critical role of the OsSTK38 S322 site in its kinase activity is highlighted. Furthermore, OsCycC, a component of the Mediator complex, was identified as a substrate of OsSTK38, with enhancement by OsMOB1A. Notably, OsSTK38 phosphorylates the T33 site of OsCycC. The phosphorylation of OsCycC by OsSTK38 influenced its interaction with the transcription factor KNOTTED-LIKE HOMEOBOX OF ARABIDOPSIS THALIANA 7 (OsKNAT7). Genetic analysis confirmed that OsMOB1A, OsSTK38 and OsCycC function in a common pathway to regulate grain size and weight. Taken together, our findings revealed a connection between the Hippo signalling pathway and the Cyclin-Dependent Kinase (CDK) module in eukaryotes. Moreover, they provide insights into the molecular mechanisms linked to yield-related traits and propose innovative breeding strategies for high-yielding varieties.

SHORT ROOT and INDETERMINATE DOMAIN family members govern PIN-FORMED expression to regulate minor vein differentiation in rice.

C3 and C4 grasses directly and indirectly provide the vast majority of calories to the human diet, yet our understanding of the molecular mechanisms driving photosynthetic productivity in grasses is largely unexplored. Ground meristem cells divide to form mesophyll or vascular initial cells early in leaf development in C3 and C4 grasses. Here we define a genetic circuit composed of SHORT ROOT (SHR), INDETERMINATE DOMAIN (IDD), and PIN-FORMED (PIN) family members that specifies vascular identify and ground cell proliferation in leaves of both C3 and C4 grasses. Ectopic expression and loss-of-function mutant studies of SHR paralogs in the C3 plant Oryza sativa (rice) and the C4 plant Setaria viridis (green millet) revealed the roles of these genes in both minor vein formation and ground cell differentiation. Genetic and in vitro studies further suggested that SHR regulates this process through its interactions with IDD12 and 13. We also revealed direct interactions of these IDD proteins with a putative regulatory element within the auxin transporter gene PIN5c. Collectively, these findings indicate that a SHR-IDD regulatory circuit mediates auxin transport by negatively regulating PIN expression to modulate minor vein patterning in the grasses.

Effect of aqueous extract of Millettia speciosa Champ on intestinal health maintenance and immune enhancement of Cyprinus carpio.

Millettia speciosa Champ (MSP) is a natural Chinese herb that improves gastrointestinal health and enhances animal immunity. An 8-week feeding trial with different MSP levels (0, 150, 300, and 600 mg/kg) was conducted to evaluate the promotive effects of MSP in Cyprinus carpio. Results indicate that MSP improved intestinal immunity to some extent evidenced by the immuno-antioxidant parameters and the 16S rRNA in the Illumina MiSeq platform. With the analysis of transcriptome sequencing, 4685 differentially expressed genes (DEGs) were identified, including 2149 up-regulated and 2536 down-regulated. According to the GO and KEGG enrichments, DEGs were mainly involved in the immune system. Transcriptional expression of the NOD-like signaling pathway and key genes retrieved from the transcriptome database confirmed that innate immunity was improved in response to dietary MSP administration. Therefore, MSP could be used as a feed supplement that enhances immunity. This may provide insight into Chinese herb additive application in aquaculture production.

Genistein alleviates doxorubicin-induced cardiomyocyte autophagy and apoptosis via ERK/STAT3/c-Myc signaling pathway in rat model.

Doxorubicin (Dox) is a highly effective anti-neoplastic agent. Still, its utility in the clinic has been hindered by toxicities, including vomiting, hematopoietic suppression and nausea, with cardiotoxicity being the most serious side effect. Genistein (Gen) is a natural product with extensive biological effects, including anti-oxidation, anti-tumor, and cardiovascular protection. This study evaluated whether Gen protected the heart from Dox-induced cardiotoxicity and explored the underlying mechanisms. Male Sprague-Dawley (SD) rats were categorized into control (Ctrl), genistein (Gen), doxorubicin (Dox), genistein 20 mg/kg/day + doxorubicin (Gen20 + Dox) and genistein 40 mg/kg/day + doxorubicin (Gen40 + Dox) groups. Six weeks after injection, immunohistochemistry (IHC), transmission electron microscopy (TEM), and clinical cardiac function analyses were performed to evaluate the effects of Dox on cardiac function and structural alterations. Furthermore, each heart histopathological lesions were given a score of 0-3 in compliance with the articles for statistical analysis. In addition, molecular and cellular response of H9c2 cells toward Dox were evaluated through western blotting, Cell Counting Kit-8 (CCK8), AO staining and calcein AM/PI assay. Dox (5 µM in vitro and 18 mg/kg in vivo) was used in this study. In vivo, low-dose Gen pretreatment protected the rat against Dox-induced cardiac dysfunction and pathological remodeling. Gen inhibited extracellular signal-regulated kinase1/2 (ERK1/2)'s phosphorylation, increased the protein levels of STAT3 and c-Myc, and decreased the autophagy and apoptosis of cardiomyocytes. U0126, a MEK1/2 inhibitor, can mimic the effect of Gen in protecting against Dox-induced cytotoxicity both in vivo and in vitro. Molecular docking analysis showed that Gen forms a stable complex with ERK1/2. Gen protected the heart against Dox-induced cardiomyocyte autophagy and apoptosis through the ERK/STAT3/c-Myc signaling pathway.

Metabolic Characteristics and Discriminative Diagnosis of Growth Hormone Deficiency and Idiopathic Short Stature in Preadolescents and Adolescents.

Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the most common types of short stature (SS), but little is known about their pathogenesis, and even less is known about the study of adolescent SS. In this study, nuclear magnetic resonance (NMR)-based metabolomic analysis combined with least absolute shrinkage and selection operator (LASSO) were performed to identify the biomarkers of different types of SS (including 94 preadolescent GHD (PAG), 61 preadolescent ISS (PAI), 43 adolescent GHD (ADG), and 19 adolescent ISS (ADI)), and the receiver operating characteristic curve (ROC) was further used to evaluate the predictive power of potential biomarkers. The results showed that fourteen, eleven, nine, and fifteen metabolites were identified as the potential biomarkers of PAG, PAI, ADG, and ADI compared with their corresponding controls, respectively. The disturbed metabolic pathways in preadolescent SS were mainly carbohydrate metabolism and lipid metabolism, while disorders of amino acid metabolism played an important role in adolescent SS. The combination of aspartate, ethanolamine, phosphocholine, and trimethylamine was screened out to identify PAI from PAG, and alanine, histidine, isobutyrate, methanol, and phosphocholine gave a high classification accuracy for ADI and ADC. The differences in metabolic characteristics between GHD and ISS in preadolescents and adolescents will contribute to the development of individualized clinical treatments in short stature.

Metabolic characteristics and pathogenesis of precocious puberty in girls: the role of perfluorinated compounds.

BACKGROUND: Precocious puberty (PP) in girls is traditionally defined as the onset of breast development before the age of 8 years. The specific biomarkers of premature thelarche (PT) and central precocious puberty (CPP) girls are uncertain, and little is known about their metabolic characteristics driven by perfluorinated compounds (PFCs) and clinical phenotype. This study aimed to screen specific biomarkers of PT and CPP and elucidate their underlying pathogenesis. The relationships of clinical phenotype-serum PFCs-metabolic characteristics were also explored to reveal the relationship between PFCs and the occurrence and development of PT and CPP. METHODS: Nuclear magnetic resonance (NMR)-based cross-metabolomics strategy was performed on serum from 146 PP (including 30 CPP, 40 PT, and 76 unspecified PP) girls and 64 healthy girls (including 36 prepubertal and 28 adolescent). Specific biomarkers were screened by the uni- and multivariate statistical analyses. The relationships between serum PFCs and clinical phenotype were performed by correlation analysis and weighted gene co-expression network analysis to explore the link of clinical phenotype-PFCs-metabolic characteristics in PT and CPP. RESULTS: The disordered trend of pyruvate and butyrate metabolisms (metabolites mapped as formate, ethanol, and 3-hydroxybutyrate) were shared and kept almost consistent in PT and CPP. Eight and eleven specific biomarkers were screened for PT and CPP, respectively. The area under curve of specific biomarker combination was 0.721 in CPP vs. prepubertal, 0.972 in PT vs. prepubertal, 0.646 in CPP vs. prepubertal integrated adolescent, and 0.822 in PT vs. prepubertal integrated adolescent, respectively. Perfluoro-n-heptanoic acid and perfluoro-n-hexanoic acid were statistically different between PT and CPP. Estradiol and prolactin were significantly correlated with PFCs in CPP and PT. Clinical phenotypes and PFCs drive the metabolic characteristics and cause metabolic disturbances in CPP and PT. CONCLUSIONS: The elevation of formate, ethanol, and 3-hydroxybutyrate may serve as the early diagnostic indicator for PP in girls. But the stratification of PP still needs to be further determined based on the specific biomarkers. Specific biomarkers of CPP and PT exhibited good sensitivity and can facilitate the classification diagnosis of CPP and PT. PFC exposure is associated with endocrine homeostasis imbalance. PFC exposure and/or endocrine disturbance directly or indirectly drive metabolic changes and form overall metabolic network perturbations in CPP and PT.

OsbHLH92, in the noncanonical brassinosteroid signaling pathway, positively regulates leaf angle and grain weight in rice.

Modifications of plant architecture can increase planting density, regulate photosynthesis, and improve crop yields. Many basic helix-loop-helix (bHLH) transcription factors participate in the brassinosteroid (BR) signaling pathway and are critical for plant architecture morphogenesis in rice. However, the number of identified bHLH genes suitable for improving production value is still limited. In this study, we cloned Lam1, encoding the typical bHLH transcription factor OsbHLH92. OsbHLH92 knockout (KO) lines exhibit erect leaves. Decreases in the number and size of parenchyma cell layers on the adaxial side of the lamina joint in KO lines were the main reason for the decreased leaf angle. Genetic experiments verify that OsBU1 and its homologs are downstream of OsbHLH92, which is involved in the noncanonical RGA1-mediated BR signaling pathway. OsbHLH91, an OsbHLH92 homolog, plays both conserved and differentiated roles relative to OsbHLH92. Notably, OsbHLH92-KO lines show erect leaves without the acquisition of adverse agronomic traits. Moreover, by driving a specific panicle promoter, OsbHLH92 can greatly increase productivity by at least 10%. This study identifies new components of the BR signaling pathway, demonstrates the importance of OsbHLH92 in improving planting density and crop productivity, and broadens our knowledge of typical and atypical bHLH family members in rice.

Colonization of multidrug-resistant Gram-negative bacteria increases risk of surgical site infection after hemorrhoidectomy: a cross-sectional study of two centers in southern China.

PURPOSE: The present study aims to determine the rectoanal colonization rate and risk factors for the colonization of present multidrug-resistant bacteria (MDRBs). In addition, the relationship between MDRB colonization and surgical site infection (SSI) following hemorrhoidectomy was explored. METHODS: A cross-sectional study was conducted in the Department of Colorectal Surgery of two hospitals. Patients with hemorrhoid disease, who underwent hemorrhoidectomy, were included. The pre-surgical screening of multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization was performed using rectal swabs on the day of admission. Then, the MDRB colonization rate was determined through the rectal swab. Logistic regression models were established to determine the risk factors for MDRB colonization and SSI after hemorrhoidectomy. A p-value of < 0.05 was considered statistically significant. RESULTS: A total of 432 patients met the inclusion criteria, and the MDRB colonization prevalence was 21.06% (91/432). The independent risk factors for MDRB colonization were as follows: patients who received ≥ 2 categories of antibiotic treatment within 3 months (odds ratio (OR): 3.714, 95% confidence interval (CI): 1.436-9.605, p = 0.007), patients with inflammatory bowel disease (IBD; OR: 6.746, 95% CI: 2.361-19.608, p < 0.001), and patients with high serum uric acid (OR: 1.006, 95% CI: 1.001-1.010, p = 0.017). Furthermore, 41.57% (37/89) of MDRB carriers and 1.81% (6/332) of non-carriers developed SSIs, with a total incidence of 10.21% (43/421). Based on the multivariable model, the rectoanal colonization of MDRBs (OR: 32.087, 95% CI: 12.052-85.424, p < 0.001) and hemoglobin < 100 g/L (OR: 4.130, 95% CI: 1.556-10.960, p = 0.004) were independently associated with SSI after hemorrhoidectomy. CONCLUSION: The rectoanal colonization rate of MDRBs in hemorrhoid patients is high, and this was identified as an independent risk factor for SSI after hemorrhoidectomy.

Identification of potential biomarkers in malnutrition children with severity by 1H-NMR-based metabolomics: a preliminary study in the Chinese population.

PURPOSE: Child malnutrition is a global public health problem, but the underlying pathophysiologic mechanisms with severity remain poorly understood, and the potential biomarkers served to the clinical diagnosis are still not available. This study aimed to identify the serum metabolic characteristics of malnourished children with severity. METHODS: Fasted overnight serum samples were collected following clinical standard procedures among 275 malnourished and 199 healthy children from the Women and Children's Hospital, Xiamen University Child Health Department from July 2020 to May 2022. Nuclear magnetic resonance (NMR)-based metabolomics strategy was applied to identify the potential serum biomarkers of malnutrition from 275 malnourished children aged 4 to 84 months with mild (Mil, 199 cases), moderate (Mod, 101 cases), and severe (Sev, 7 cases) malnutrition. RESULTS: Ten, fifteen, and fifteen differential metabolites were identified from the Mil, Mod, and Sev malnutrition groups, respectively. Eight common metabolites, including increased acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, and decreased alanine, methionine, and N-acetyl-glycoprotein, could be the potential biomarkers for malnourished children. The altered metabolic pathways were mainly related to energy metabolism and amino acid metabolism via the network-based pathway enrichment. CONCLUSION: Eight potential biomarkers, including acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, alanine, methionine, and N-acetyl-glycoprotein, could characterize the child malnutrition. Child malnutrition-induced abnormal energy metabolism, impaired nutrition utilization and the reduced nutrient availability, and more metabolic disturbance will appear with the severity. Our results are valuable for further studies on the etiology and pathogenesis of malnutrition for clinical intervention and improvement.

TREM2 expression on the microglia resolved lead exposure-induced neuroinflammation by promoting anti-inflammatory activities.

Neurotoxicity caused by environmental lead (Pb) pollution is a worldwide public health concern, and developing a therapeutic strategy against Pb-induced neurotoxicity is an important area in the current research. Our prior research has demonstrated the significant involvement of microglia-mediated inflammatory responses in the manifestation of Pb-induced neurotoxicity. Additionally, the suppression of proinflammatory mediator activity significantly mitigated the toxic effects associated with Pb exposure. Recent studies have highlighted the critical role of the triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of neurodegenerative disorders. TREM2 exerted protective effects on inflammation, but whether TREM2 is involved in Pb-induced neuroinflammation is poorly understood. In the present study, cell culture experiments and animal models were designed to investigate the role of TREM2 in Pb's neuroinflammation. We examined the impact of pro- and anti-inflammatory cytokines involved in Pb-induced neuroinflammation. Flow cytometry and microscopy techniques were applied to detect microglia phagocytosis and migration ability. Our results showed that Pb treatment significantly downregulated TREM2 expression and altered the localization of TREM2 expression in microglia. The protein expression of TREM2 was restored, and the inflammatory responses provoked by Pb exposure were ameliorated upon the overexpression of TREM2. Furthermore, the phagocytosis and migratory capabilities of microglia, which were impaired due to Pb exposure, were alleviated by TREM2 overexpression. Our in vitro findings were corroborated in vivo, demonstrating that TREM2 regulates the anti-inflammatory functions of microglia, thereby mitigating Pb-induced neuroinflammation. Our results provide insights into the detailed mechanism by which TREM2 alleviates Pb-induced neuroinflammation and suggest that activating the anti-inflammatory functions of TREM2 may represent a potential therapeutic strategy against environmental Pb-induced neurotoxicity.

Defense against membership inference attack in graph neural networks through graph perturbation.

Graph neural networks have demonstrated remarkable performance in learning node or graph representations for various graph-related tasks. However, learning with graph data or its embedded representations may induce privacy issues when the node representations contain sensitive or private user information. Although many machine learning models or techniques have been proposed for privacy preservation of traditional non-graph structured data, there is limited work to address graph privacy concerns. In this paper, we investigate the privacy problem of embedding representations of nodes, in which an adversary can infer the user's privacy by designing an inference attack algorithm. To address this problem, we develop a defense algorithm against white-box membership inference attacks, based on perturbation injection on the graph. In particular, we employ a graph reconstruction model and inject a certain size of noise into the intermediate output of the model, i.e., the latent representations of the nodes. The experimental results obtained on real-world datasets, along with reasonable usability and privacy metrics, demonstrate that our proposed approach can effectively resist membership inference attacks. Meanwhile, based on our method, the trade-off between usability and privacy brought by defense measures can be observed intuitively, which provides a reference for subsequent research in the field of graph privacy protection.

HD-ZIP IV gene Roc8 regulates the size of bulliform cells and lignin content in rice.

The morphology of bulliform cells located on the upper epidermis of leaves is one of the most important cell structures affecting leaf shape. Although many mechanisms regulating the development of bulliform cells have been reported, the fine regulatory mechanisms governing this process have rarely been described. To identify novel components regulating rice leaf morphology, a mutant showing a constitutively rolling phenotype from the seedling stage to flowering, known as crm1-D, was selected for further analysis. Anatomical analyses in crm1-D were attributable to the size reduction of bulliform cells. The crm1-D was controlled by a single dominant nuclear gene. Map-based cloning revealed that Roc8, an HD zipper class IV family member, was responsible for the crm1-D phenotype. Notably, the 50-bp sequence in the 3'-untranslated region (3'-UTR) of the Roc8 gene represses Roc8 at the translational level. Moreover, the roc8 knockdown lines notably increased the size of bulliform cells. A series of assays revealed that Roc8 negatively regulates the size of bulliform cells. Unexpectedly, Roc8 was also observed to positively mediate lignin biosynthesis without incurring a production penalty. The above results show that Roc8 may have a practical application in cultivating materials with high photosynthetic efficiency and low lignin content.

Characteristics of Nosocomial Infections in Children Screened for SARS-CoV-2 Infection in China.

BACKGROUND This study summarizes the characteristics of children screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reports the case of 1 child who was diagnosed with SARS-CoV-2 infection in Guangzhou Women and Children's Medical Center and the cases of his family members. MATERIAL AND METHODS The medical records of 159 children who were admitted to our hospital from January 23 to March 20, 2020, were retrospectively analyzed. Samples from pharyngeal or/and anal swabs were subjected to reverse-transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 within 12 h of patient admission; a second RT-PCR test was done 24 h after the first test. RESULTS Of the 159 patients, 151 patients had epidemiological histories, 14 patients had cluster onset, and 8 patients had no epidemiological history but had symptoms similar to coronavirus disease 2019 (COVID-19). The most common symptom was fever (n=125), followed by respiratory and gastrointestinal symptoms. A 7-year-old boy in a cluster family from Wuhan was confirmed with asymptomatic SARS-CoV-2 infection with ground-glass opacity shadows on his lung computed tomography scan, and his swab RT-PCR test had not turned negative until day 19 of his hospitalization. In patients who did not test positive for SARS-CoV-2, influenza, respiratory syncytial virus, and adenovirus were observed. A total of 158 patients recovered, were discharged, and experienced no abnormalities during follow-up. CONCLUSIONS For SARS-CoV-2 nosocomial infections, taking a "standard prevention & contact isolation & droplet isolation & air isolation" strategy can prevent infection effectively. Children with clustered disease need close monitoring.

Overexpression of the WOX gene STENOFOLIA improves biomass yield and sugar release in transgenic grasses and display altered cytokinin homeostasis.

Lignocellulosic biomass can be a significant source of renewable clean energy with continued improvement in biomass yield and bioconversion strategies. In higher plants, the leaf blade is the central energy convertor where solar energy and CO2 are assimilated to make the building blocks for biomass production. Here we report that introducing the leaf blade development regulator STENOFOLIA (STF), a WOX family transcription factor, into the biofuel crop switchgrass, significantly improves both biomass yield and sugar release. We found that STF overexpressing switchgrass plants produced approximately 2-fold more dry biomass and release approximately 1.8-fold more solubilized sugars without pretreatment compared to controls. The biomass increase was attributed mainly to increased leaf width and stem thickness, which was also consistent in STF transgenic rice and Brachypodium, and appeared to be caused by enhanced cell proliferation. STF directly binds to multiple regions in the promoters of some cytokinin oxidase/dehydrogenase (CKX) genes and represses their expression in all three transgenic grasses. This repression was accompanied by a significant increase in active cytokinin content in transgenic rice leaves, suggesting that the increase in biomass productivity and sugar release could at least in part be associated with improved cytokinin levels caused by repression of cytokinin degrading enzymes. Our study provides a new tool for improving biomass feedstock yield in bioenergy crops, and uncovers a novel mechanistic insight in the function of STF, which may also apply to other repressive WOX genes that are master regulators of several key plant developmental programs.

Role of microRNA-122 in microcystin-leucine arginine-induced dysregulation of hepatic iron homeostasis in mice.

Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide hepatotoxin produced by cyanobacteria. MicroRNA-122 (miR-122) is specifically expressed in the liver. This study focuses on the role of miR-122 in MC-LR-induced dysregulation of hepatic iron homeostasis in C57BL/6 mice. The thirty mice were randomly divided into five groups (Control, 12.5 µg/kg·BW MC-LR, 25 µg/kg·BW MC-LR, Negative control agomir and 25 µg/kg·BW MC-LR + miR-122 agomir). The results show that MC-LR decreases the expressions of miR-122, Hamp, and its related regulators, while increasing the content of hepatic iron and the expressions of FPN1 and Tmprss6. Furthermore, miR-122 agomir pretreatment improves MC-LR induced dysregulation of hepatic iron homeostasis by arousing the related regulators and reducing the expression of Tmprss6. These results suggest that miR-122 agomir can prevent the accumulation of hepatic iron induced by MC-LR, which may be related to the regulation of hepcidin by BMP/SMAD and IL-6/STAT signaling pathways.

Epigenetic modification of H3K4 and oxidative stress are involved in MC-LR-induced apoptosis in testicular cells of SD rats.

Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide, produced by aquatic cyanobacteria such as microcystis, with strong reproductive toxicity which poses greater threat to the reproductive abilities of humans and animals. By exploring the role of trimethylation of histone H3 at lysine 4 (H3K4me3) and the role of oxidative stress in MC-LR-induced apoptosis in testicular Sertoli cells in Sprague-Dawley (SD) rats, this study indicated that MC-LR increased the expression levels of apoptosis-related genes by raising the levels of H3K4me3. 5'-Deoxy-5'-methylthioadenosine (MTA), the inhibitor of H3K4me3, reduced apoptosis, indicating for the first time that epigenetic modification is closely related to the testicular reproductive toxicity induced by MC-LR. MC-LR also induced oxidative stress by stimulating the generation of reactive oxygen species (ROS), and subsequently triggering mitochondria-mediated apoptotic pathway by decreasing mitochondrial membrane potential and increasing the levels of Bax, Bcl-2, Caspase-3, and so on. MC-LR-induced apoptosis of testicular cells could be decreased after pretreatment with oxidative stress inhibitor N-acetyl-cysteine (NAC). Furthermore, the pathological damage to mitochondria and testes were observed in SD rats. These results show that MC-LR can induce apoptosis by raising the levels of H3K4me3, and pretreatment with MTA can ameliorate the MC-LR-induced apoptosis of cocultured cells by lowering the levels of H3K4me3. Furthermore, NAC has a protective effect on MC-LR-induced apoptosis of testicular cells in SD rats by inhibiting the oxidative stress.

The RNA editing factor DUA1 is crucial to chloroplast development at low temperature in rice.

Low temperature stress hinders plant growth and chloroplast development and can limit the geographic range of cultivars. In rice, japonica cultivars have greater chilling tolerance than indica cultivars, but the molecular mechanism underlying chilling tolerance is unclear. Here, we report an RNA-binding protein, DUA1, cloned from the indica cultivar Dular, which exhibits a deficiency in chloroplast development at an early stage of development under low-temperature conditions. DUA1 shares high sequence homology with the pentatricopeptide repeat family and functions in plastid RNA editing under low-temperature conditions. Our data suggest that DUA1 can bind to the plastid-encoded rps8-182 transcript and disruption of DUA1 activity impairs editing. The RNA editing cofactor WSP1, a partner of DUA1, also participates in chloroplast development at low temperature. Western blot analysis indicates that WSP1 enhances DUA1 stability under low temperatures. DUA1 sequence analyses of rice core germplasm revealed that three major haplotypes of DUA1 and one haplotype showed substantial differences in chlorophyll content under low-temperature conditions. Variation at DUA1 may play an important role in the adaptation of rice to different growing regions.

TWI1 regulates cell-to-cell movement of OSH15 to control leaf cell fate.

Cell pattern formation in plant leaves has attracted much attention from both plant biologists and breeders. However, in rice, the molecular mechanism remains unclear. Here, we describe the isolation and functional characterization of TWISTED-LEAF1 (TWI1), a critical gene involved in the development of the mestome sheath, vascular bundle sheath, interveinal mesophyll and sclerenchyma in rice leaves. Mutant twi1 plants have twisted leaves which might be caused by the compromised development and disordered patterning of bundle sheath, sclerenchyma and interveinal mesophyll cells. Expression of TWI1 can functionally rescue these mutant phenotypes. TWI1 encodes a transcription factor binding protein that interacts with OSH15, a class I KNOTTED1-like homeobox (KNOX) transcription factor. The cell-to-cell trafficking of OSH15 is restricted through its interaction with TWI1. Knockout or knockdown of OSH15 in twi1 rescues the twisted leaf phenotype. These studies reveal a key factor controlling cell pattern formation in rice leaves.

Estrogen regulation of cardiac cAMP-L-type Ca2+ channel pathway modulates sex differences in basal contraction and responses to ß2AR-mediated stress in left ventricular apical myocytes.

BACKGROUNDS/AIM: Male and female hearts have many structural and functional differences. Here, we investigated the role of estrogen (E2) in the mechanisms of sex differences in contraction through the cAMP-L-type Ca2+channel pathway in adult mice left ventricular (LV) apical myocytes at basal and stress state. METHODS: Isolated LV apical myocytes from male, female (Sham) and ovariectomised mice (OVX) were used to investigate contractility, Ca2+ transients and L-type Ca2+ channel (LTCC) function. The levels of ß2AR, intracellular cAMP, phosphodiesterase (PDE 3 and PDE 4), RyR2, PLB, SLN, and SERCA2a were compared among the experimental groups. RESULTS: We found that (1) intracellular cAMP, ICaL density, contraction and Ca2+ transient amplitudes were larger in Sham and OVX + E2 myocytes compared to male and OVX. (2) The mRNA expression of PDE 3 and 4 were lower in Sham and OVX + E2 groups compared with male and OVX groups. Treatment of myocytes with IBMX (100 µM) increased contraction and Ca2+ transient amplitude in both sexes and canceled differences between them. (3) ß2AR-mediated stress decreased cAMP concentration and peak contraction and Ca2+ transient amplitude only in male and OVX groups but not in Sham or OVX + E2 groups suggesting a cardioprotective role of E2 in female mice. (4) Pretreatment of OVX myocytes with GPR30 antagonist G15 (100 nM) abolished the effects of E2, but ERα and ERß antagonist ICI 182,780 (1 µM) did not. Moreover, activation of GPR30 with G1 (100 nM) replicated the effects of E2 on cAMP, contraction and Ca2+ transient amplitudes suggesting that the acute effects of E2 were mediated by GPR30 via non-genomic signaling. (5) mRNA expression of RyR2 was higher in myocytes from Sham than those of male while PLB and SLN were higher in male than Sham but no sex differences were observed in the mRNA of SERCA2a. CONCLUSION: Collectively, these results demonstrate that E2 modulates the expression of genes related to the cAMP-LTCC pathway and contributes to sex differences in cardiac contraction and responses to stress. We also show that estrogen confers cardioprotection against cardiac stress by non-genomic acute signaling via GPR30.

The adverse health effects of bisphenol A and related toxicity mechanisms.

Bisphenol A (BPA) is an industrial component commonly used in synthesis of polycarbonate plastics, epoxy resin and other polymer materials. Due to its mass productions and widespread applications, the presence of BPA is ubiquitous in the environment. BPA can enter the body via different ways such as digestive tract, respiratory tract and dermal tract. As an endocrine disruptor, BPA has estrogen-like and anti-androgen effects causing damages to different tissues and organs, including reproductive system, immune system and neuroendocrine system, etc. Recently, it has been shown that BPA could induce carcinogenesis and mutagenesis in animal models. Here, the underlying mechanisms of BPA-induced multi-organ toxicity were well summarized, involving the receptor pathways, disruption of neuroendocrine system, inhibition of enzymes, modulation of immune and inflammatory responses, as well as genotoxic and epigenetic mechanisms. The aim of this review is to compile the available current research data regarding BPA and provide an overview of the current status of BPA exposure and relevant health effects covering reproductive, developmental, metabolic, immuno, respiratory, hepatic and renal toxicity and carcinogenesis of BPA. This review provides comprehensive data of BPA toxicity on human health and related mechanisms. We also identify any missing data which should be addressed by further studies.