ABSTRACT
Fertilization introduces parental genetic information into the zygote to guide embryogenesis. Parental contributions to postfertilization development have been discussed for decades, and the data available show that both parents contribute to the zygotic transcriptome, suggesting a paternal role in early embryogenesis1-6. However, because the specific paternal effects on postfertilization development and the molecular pathways underpinning these effects remain poorly understood, paternal contribution to early embryogenesis and plant development has not yet been adequately demonstrated7. Here our research shows that TREE1 and its homologue DAZ3 are expressed exclusively in Arabidopsis sperm. Despite presenting no evident defects in sperm development and fertilization, tree1 daz3 unexpectedly led to aberrant differentiation of the embryo root stem cell niche. This defect persisted in seedlings and disrupted root tip regeneration, comparable to congenital defects in animals. TREE1 and DAZ3 function by suppression of maternal RKD2 transcription, thus mitigating the detrimental maternal effects from RKD2 on root stem cell niche. Therefore, our findings illuminate how genetic deficiencies in sperm can exert enduring paternal effects on specific plant organ differentiation and how parental-of-origin genes interact to ensure normal embryogenesis. This work also provides a new concept of how gamete quality or genetic deficiency can affect specific plant organ formation.
ABSTRACT
Body axis establishment is one of the earliest patterning events in plant embryogenesis. Asymmetric zygote division is critical for apical-basal axis formation in Arabidopsis (Arabidopsis thaliana). However, how the orientation of the cell division plane is regulated and its relation to apical-basal axis establishment and proper position of embryos in grasses remain poorly understood. By characterizing mutants of 3 rice (Oryza sativa) WUSCHEL HOMEOBOX9 (WOX9) genes, whose paralogs in Arabidopsis play essential roles in zygotic asymmetric cell division and cell fate determination, we found 2 kinds of independent embryonic defects: topsy-turvy embryos, in which apical-basal axis twists from being parallel to the longitudinal axis of the seed to being perpendicular; and organ-less embryos. In contrast to their Arabidopsis orthologs, OsWOX9s displayed dynamic distribution during embryo development. Both DWT1/OsWOX9A and DWL2/WOX9C play major roles in the apical-basal axis formation and initiation of stem cells. In addition, DWT1 has a distinct function in regulating the first few embryonic cell divisions to ensure the correct orientation of the embryo in the ovary. In summary, DWT1 acts in 2 steps during rice embryo pattern formation: the initial zygotic division, and with DWL2 to establish the main body axes and stem cell fate 2 to 3 d after pollination.
Subject(s)
Gene Expression Regulation, Plant , Oryza , Plant Proteins , Seeds , Oryza/genetics , Oryza/embryology , Oryza/growth & development , Seeds/genetics , Seeds/growth & development , Seeds/embryology , Plant Proteins/genetics , Plant Proteins/metabolism , Mutation/genetics , Body Patterning/genetics , Gene Expression Regulation, Developmental , Cell Division/geneticsABSTRACT
Chinese bayberry (Morella rubra) is a fruit tree with a remarkable variation in fruit color, ranging from white to dark red as determined by anthocyanin content. In dark red "Biqi" (BQ), red "Dongkui" (DK), pink "Fenhong" (FH), and white "Shuijing" (SJ), we identified an anthocyanin-related MYB transcription factor-encoding gene cluster of four members, i.e. MrMYB1.1, MrMYB1.2, MrMYB1.3, and MrMYB2. Collinear analysis revealed that the MYB tandem cluster may have occurred in a highly conserved region of many eudicot genomes. Two alleles of MrMYB1.1 were observed; MrMYB1.1-1 (MrMYB1.1n) was a full-length allele and homozygous in "BQ", MrMYB1.1-2 (MrMYB1.1d) was a nonfunctional allele with a single base deletion and homozygous in "SJ", and MrMYB1.1n/MrMYB1.1d were heterozygous in "DK" and "FH". In these four cultivars, expression of MrMYB1.1, MrMYB1.2, and MrMYB2 was enhanced during ripening. Both alleles were equally expressed in MrMYB1.1n/MrMYB1.1d heterozygous cultivars as revealed by a cleaved amplified polymorphic sequence marker. Expression of MrMYB1.3 was restricted to some dark red cultivars only. Functional characterization revealed that MrMYB1.1n and MrMYB1.3 can induce anthocyanin accumulation while MrMYB1.1d, MrMYB1.2, and MrMYB2 cannot. DNA-protein interaction assays indicated that MrMYB1.1n and MrMYB1.3 can directly bind to and activate the promoters of anthocyanin-related genes via interaction with a MYC-like basic helix-loop-helix protein MrbHLH1. We concluded that the specific genotype of MrMYB1.1 alleles, as well as the exclusive expression of MrMYB1.3 in some dark red cultivars, contributes to fruit color variation. The study provides insights into the mechanisms for regulation of plant anthocyanin accumulation by MYB tandem clusters.
Subject(s)
Fruit , Gene Expression Regulation, Plant , Multigene Family , Pigmentation , Plant Proteins , Transcription Factors , Fruit/genetics , Fruit/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Pigmentation/genetics , Anthocyanins/metabolism , Phylogeny , Alleles , Genes, Plant , Molecular Sequence Data , Amino Acid Sequence , ColorABSTRACT
During angiosperm male gametogenesis, microspores divide to produce a vegetative cell (VC) and a male germline (MG), each with distinct cell fates. The mechanism underlying determination of the MG cell/VC fate remains an important area of research, with many unanswered questions. Here, we report that H3K27me3 is essential for VC fate commitment in male Arabidopsis thaliana gametophytes; H3K27me3 erasure contributes to MG cell fate initiation. VC-targeted H3K27me3 erasure disturbed VC development and shifted the VC fate toward a gamete destination, which suggests that MG cells require H3K27me3 erasure to trigger gamete cell fate. Multi-omics and cytological analyses confirmed the occurrence of extensive cell identity transition due to H3K27me3 erasure. Therefore, we experimentally confirmed that MG cell/VC fate is epigenetically regulated. H3K27 methylation plays a critical role in guiding MG cell/VC fate determination for pollen fertility in Arabidopsis. Our work also provides evidence for two previous hypotheses: the germline cell fate is specified by the differential distribution of unknown determinants and VC maintains the default microspore program (i.e. the H3K27me3 setting) while MG requires reprogramming.
Subject(s)
Arabidopsis , Histones , Arabidopsis/metabolism , Cell Lineage , Histones/genetics , Histones/metabolism , Methylation , Pollen/metabolismABSTRACT
Acute kidney injury (AKI) is closely related to lysosomal dysfunction and ferroptosis in renal tubular epithelial cells (TECs), for which effective treatments are urgently needed. Although selenium nanoparticles (SeNPs) have emerged as promising candidates for AKI therapy, their underlying mechanisms have not been fully elucidated. Here, we investigated the effect of SeNPs on hypoxia/reoxygenation (H/R)-induced ferroptosis and lysosomal dysfunction in TECs in vitro and evaluated their efficacy in a murine model of ischemia/reperfusion (I/R)-AKI. We observed that H/R-induced ferroptosis was accompanied by lysosomal Fe2+ accumulation and dysfunction in TECs, which was ameliorated by SeNPs administration. Furthermore, SeNPs protected C57BL/6 mice against I/R-induced inflammation and ferroptosis. Mechanistically, we found that lysosomal Fe2+ accumulation and ferroptosis were associated with the excessive activation of NCOA4-mediated ferritinophagy, a process mitigated by SeNPs through the upregulation of X-box binding protein 1 (XBP1). Downregulation of XBP1 promoted ferritinophagy and partially counteracted the protective effects of SeNPs on ferroptosis inhibition in TECs. Overall, our findings revealed a novel role for SeNPs in modulating ferritinophagy, thereby improving lysosomal function and attenuating ferroptosis of TECs in I/R-AKI. These results provide evidence for the potential application of SeNPs as therapeutic agents for the prevention and treatment of AKI.
Subject(s)
Ferroptosis , Nanoparticles , Reperfusion Injury , Selenium , X-Box Binding Protein 1 , Animals , Humans , Male , Mice , Acute Kidney Injury/pathology , Acute Kidney Injury/metabolism , Acute Kidney Injury/drug therapy , Autophagy/drug effects , Ferritins/metabolism , Ferroptosis/drug effects , Lysosomes/metabolism , Lysosomes/drug effects , Mice, Inbred C57BL , Nanoparticles/chemistry , Nuclear Receptor Coactivators/metabolism , Nuclear Receptor Coactivators/genetics , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Selenium/pharmacology , Selenium/administration & dosage , Signal Transduction/drug effects , X-Box Binding Protein 1/metabolism , X-Box Binding Protein 1/geneticsABSTRACT
OBJECTIVE: To analyze the epidemic characteristics of common respiratory tract infection pathogens in children with respiratory tract infection, and provide scientific basis for the prevention and control of respiratory tract infection. METHODS: A retrospective collection of clinical data was conducted on 11,538 children with respiratory tract infections at Luoyang Maternal and Child Health Hospital from December 2022 to November 2023. The types of respiratory tract infections, including upper and lower respiratory tract infections, as well as five respiratory pathogens: influenza A virus (influenza A), influenza B virus (influenza B virus, adenovirus (ADV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP) infections, were analyzed and compared for different genders, ages, temperatures, and air quality in different months; And the changes of five pathogens in children with respiratory tract infections of different disease severity. RESULTS: From December 2022 to November 2023, a total of 11,538 children with respiratory infections were included in the analysis, including 6436 males and 5102 females, with an age of 4.92 ± 2.03 years. The proportion of upper respiratory tract infections is as high as 72.17%, and lower respiratory tract infections account for 27.83%. Among them, 2387 were positive for Flu A antigen, with a positive rate of 20.69%, 51 cases were positive for Flu B antigen, and the positive rate was 0.4%, 1296 cases were positive for adv antigen, with a positive rate of 11.23%, 868 cases were positive for RSV antigen, with a positive rate of 7.52%, 2481 cases were positive for MP IgM antibody or MP antigen, and the positive rate was 21.50%. Flu B in male children The infection rate of ADV and MP was higher than that of female children (p < 0.05); Among children in different age groups, the older the age, the older the Flu A The higher the infection rate of MP (p < 0.05), the higher the positive rate of RSV in children with younger age (p < 0.05). The positive rate of ADV in children aged 3-6 years and > 6 years was higher than that in children aged 0-3 years (p < 0.05); Flu A and MP are popular throughout the year, and the positive rate peaks during the period of temperature rise and air quality decline from February to March, and during the period of temperature drop and air quality index rise from August to November, The positive rate of RSV peaked after the turning point of temperature rise from March to April. The infection rate was higher during the period of sharp decline in air quality from March to May and sharp decline in temperature in November, The positive rate of ADV was higher at the turning point of temperature rise from February to March, and then the infection rate decreased. During the period of sharp temperature drop from August to November, the positive rate increased sharply, and the peak of infection occurred; As the disease worsens, The positive rates of Flu A, Flu B, RSV, MP and combined infection with more than two pathogens were all increased (p < 0.05). CONCLUSION: After the new coronavirus epidemic in 2022, Flu A and MP have the highest infection rate of respiratory pathogens in children, showing a peak growth in general, with epidemic characteristics changing with environmental temperature, air quality and seasons. The main disease type is upper respiratory tract infection, MP and adv infections were mainly in male children, Flu A, MP and ADV infections are more common in older children, RSV infection was more common in younger children; Flu A, Flu B, RSV and MP infection and the co infection of more than two pathogens may more easily lead to the occurrence of severe pneumonia.
Subject(s)
Influenza B virus , Respiratory Tract Infections , Humans , Female , Male , Child, Preschool , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Retrospective Studies , Child , Infant , Influenza B virus/isolation & purification , China/epidemiology , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/virology , Mycoplasma pneumoniae , Influenza A virus/isolation & purification , Respiratory Syncytial Virus, Human/isolation & purification , Respiratory Syncytial Viruses/isolation & purification , Influenza, Human/epidemiology , Influenza, Human/virology , Pneumonia, Mycoplasma/epidemiology , Pneumonia, Mycoplasma/microbiology , SeasonsABSTRACT
BACKGROUND: While prenatal exposure to alkylphenols (APs) has been demonstrated to be associated with neurodevelopmental impairments in animals, the evidence from epidemiological studies remains limited and inconclusive. This study aimed to explore the link between AP exposure during pregnancy and the intelligence quotient (IQ) of preschool children. METHODS: A total of 221 mother-child pairs from the Guangxi Zhuang Birth Cohort were recruited. Nonylphenol (NP), 4-tert-octylphenol (4-T-OP), 4-n-nonylphenol (4-N-NP), and 4-n-octylphenol were measured in maternal serum in early pregnancy. Childhood IQ was evaluated by the Fourth Edition of Wechsler Preschool and Primary Scale of the Intelligence at 3 to 6 years of age. The impact of APs on childhood IQ were evaluated by generalized linear models (GLMs), restricted cubic spline (RCS), and Bayesian kernel machine regression (BKMR). RESULTS: In GLMs, prenatal exposure to NP and the second tertile of 4-T-OP exhibited an inverse association with full-scale IQ (FSIQ) (ß = -2.38; 95% CI: -4.59, -0.16) and working memory index (WMI) (ß = -5.24; 95% CI: -9.58, -0.89), respectively. Prenatal exposure to the third tertile of 4-N-NP showed a positive association with the fluid reasoning index (ß = 4.95; 95% CI: 1.14, 8.77) in total children, as well as in girls when stratified by sex. A U-shaped relationship between maternal 4-T-OP and WMI was noted in total children and girls by RCS (all P nonlinear < 0.05). The combined effect primarily driven by NP, of maternal AP mixtures at concentrations above the 50th percentile exhibited an inverse trend on FSIQ in total children and girls in BKMR. CONCLUSIONS: Prenatal exposure to various APs affects IQ in preschool children, and there may be nonmonotonic and sex-specific effects. Further investigation across the population is required to elucidate the potential neurotoxic effects of APs.
Subject(s)
Phenols , Prenatal Exposure Delayed Effects , Male , Pregnancy , Female , Humans , Child, Preschool , Child , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/epidemiology , Bayes Theorem , China , Intelligence Tests , IntelligenceABSTRACT
The liver toxicity of alkylphenols (APs) has been demonstrated in animal studies. However, relevant epidemiological evidence is still lacking in humans, especially during pregnancy. We obtained the levels of biochemical indicators of liver function in early (<13 weeks, mean gestation=9.80±1.96 weeks) and late (≥32 weeks, mean gestation = 37.23±2.45 weeks) pregnancies from 219 pregnant women in the Guangxi Zhuang birth cohort from 2015-2017. We also examined the serum levels of APs in these pregnant women in early pregnancy. The present study aimed to investigate the correlations between the exposure of pregnant women to APs and their serum liver function indices. The results of the generalized linear model (GLM) in this study revealed that nonylphenol (NP) was positively correlated with total bilirubin (TBIL) (P=0.04) in early pregnancy, and 4-n-nonylphenol (4-N-NP) was negatively correlated with glutamyl transferase (GGT) (P=0.012). In late pregnancy, NP was positively associated with TBIL (P=0.002), and 4-tert-octylphenol (4-T-OP) was positively correlated with alanine aminotransferase (ALT) (P=0.02). Restricted cubic spline (RCS) results revealed doseresponse relationships between NP and TBIL (Poverall=0.011) and between 4-N-NP and GGT (Poverall=0.007) in early pregnancy. In late pregnancy, there were doseresponse relationships between NP and TBIL (Poverall=0.001) and between 4-T-OP and ALT (Poverall=0.033). There was also a doseresponse relationship between NP volume and GGT with an inverted 'U' shape (Poverall=0.041, Pnonlinear=0.012). Bayesian kernel machine regression modeling (BKMR) revealed that TBIL increased significantly (P<0.05) with increasing levels of coexposure to APs in both early and late pregnancy. Overall, exposure to APs during pregnancy affects maternal liver function to varying degrees. The present study provides new epidemiological evidence that exposure to alkylphenols in pregnant women interferes with liver function.
Subject(s)
Biomarkers , Liver , Phenols , Female , Humans , Pregnancy , Phenols/toxicity , Phenols/blood , China , Adult , Biomarkers/blood , Liver/drug effects , Maternal Exposure/adverse effects , Bilirubin/blood , Liver Function Tests , gamma-Glutamyltransferase/blood , Alanine Transaminase/blood , Young Adult , Environmental Pollutants/blood , Cohort StudiesABSTRACT
A 60-day feeding trial was conducted to evaluate the impact of dietary Antarctic krill meal on the reproductive performance and embryo quality of the Chinese mitten crab, Eriocheir sinensis. Three diets were formulated, incorporating varying levels of Antarctic krill meal at 0% (Diet K0), 10% (Diet K10), and 20% (Diet K20), with a control group fed razor clam Sinonovacula constricta. Each diet was randomly assigned to three replicate tanks, each stocked with 5 males and 10 females. Male and female weights were 145.38 ± 8.01 and 102.57 ± 9.73 g, respectively. The results revealed no significant differences in weight gain rate, specific growth rate, and survival rate. However, the hepatopancreatic weight and hepatopancreas index of female crabs in each group decreased, while gonadal weight and gonadosomatic index increased significantly after 60 days, with Diet K20 showing the highest values. Egg production and fecundity of female crabs reached their peak in Diet K20, with no significant differences in reproductive indices among all groups. The phospholipid content in Diet K20 was significantly higher than in the other groups (P < 0.05). Cholesterol contents in Diet K0 and the control group were significantly higher than in Diet K10 and K20 (P < 0.05). No significant differences were observed in egg diameter, egg weight, moisture, crude protein, and crude fat between the groups. The content of C20 : 2 and C20 : 4n6 was highest in Diet K0, with a significant difference compared to Diet K10 (P < 0.05). However, no significant differences were found in the total content of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids among all groups. Based on the research findings, it is recommended that the optimal level of Antarctic krill meal in diets is 20%.
ABSTRACT
BACKGROUND: The world's population is getting older. This issue is accompanied by a rise in the number of older people suffering from dementia and disability, for whom oral hygiene care is challenging. Nurses' attitudes toward providing oral care (POC) are critical for the elderly, while few studies have investigated the determinant factors of nurses' attitudes by identifying the current work pressure, resilience and self-efficacy in geriatric care facilities (GCFs). It is of great significance to explore the nurses' attitudes toward POC and associated influencing factors related to psychological aspects including resilience, self-efficacy, and stress from the workplace. METHODS: Attitudes for Providing Mouth Care (A-PMC) in Chinese version were used in this cross-sectional study with 160 nurses in 2 GCFs. Data were collected using online questionnaires and analyzed by multiple linear regression analysis. Statistically significant values were considered at p < 0.05. RESULTS: A total of 160 nurses participated in this study, with an average age of 32.86 ± 7.43. The mean score for the A-PMC was 2.81 ± 0.47. The score of A-PMC was negatively correlated with work pressure (r=-0.332, p < 0.01), and positively correlated with resilience (r = 0.735, p < 0.01) and self-efficacy (r = 0.425, p < 0.01) respectively. Multiple linear regression analyses identified that the potential influencing factors of A-PMC were education background, work hours every shift, self-efficacy, work pressure and resilience. CONCLUSIONS: The study results indicate nurses' attitudes regarding PMC were at a low level, which is influenced by many factors. To improve nurses' attitudes toward PMC and the oral hygiene (OH) of the elderly in GCFs, it is necessary to increase nurses' education and training, establish a reasonable and effective incentive mechanism to improve nurses' work motivation and other intervention measures to reduce work pressure.
Subject(s)
Attitude of Health Personnel , Nurses , Humans , Aged , Adult , Cross-Sectional Studies , Surveys and Questionnaires , Oral HygieneABSTRACT
Acute kidney injury (AKI) is the main obstacle that limits the use of cisplatin in cancer treatment. Proton pump inhibitors (PPIs), the most commonly used class of medications for gastrointestinal complications in cancer patients, have been reported to cause adverse renal events. However, the effect of PPIs on cisplatin-induced AKI remains unclear. Herein, the effect and mechanism of lansoprazole (LPZ), one of the most frequently prescribed PPIs, on cisplatin-induced AKI were investigated in vivo and in vitro. C57BL/6 mice received a single intraperitoneal (i.p.) injection of cisplatin (18 mg/kg) to induce AKI, and LPZ (12.5 or 25 mg/kg) was administered 2 hours prior to cisplatin administration and then once daily for another 2 days via i.p. injection. The results showed that LPZ significantly aggravated the tubular damage and further increased the elevated levels of serum creatinine and blood urea nitrogen induced by cisplatin. However, LPZ did not enhance cisplatin-induced tubular apoptosis, as evidenced by a lack of significant change in mRNA and protein expression of Bax/Bcl-2 ratio and TUNEL staining. Notably, LPZ increased the number of necrotic renal tubular cells compared to that by cisplatin treatment alone, which was further confirmed by the elevated necroptosis-associated protein expression of RIPK1, p-RIPK3 and p-MLKL. Furthermore, LPZ deteriorated cisplatin-induced inflammation, as revealed by the increased mRNA expression of pro-inflammatory factors including, NLRP3, IL-1ß, TNF-α and caspase 1, as well as neutrophil infiltration. Consistently, in in vitro study, LPZ increased HK-2 cell death and enhanced inflammation, compared with cisplatin treatment alone. Collectively, our results demonstrate that LPZ aggravates cisplatin-induced AKI, and necroptosis may be involved in the exacerbation of kidney damage.
Subject(s)
Antineoplastic Agents/adverse effects , Cisplatin/adverse effects , Kidney Tubular Necrosis, Acute/etiology , Kidney Tubular Necrosis, Acute/metabolism , Lansoprazole/adverse effects , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Apoptosis/drug effects , Disease Models, Animal , Drug Synergism , Kidney Tubular Necrosis, Acute/pathology , MiceABSTRACT
Parkinson disease-associated mutations within the GTPase domain Ras of complex proteins (ROC) of leucine rich repeat kinase 2 (LRRK2) result in an abnormal over-activation of its kinase domain. However, the mechanisms involved remain unclear. Recent study has shown that LRRK2 G-domain cycles between monomeric and dimeric conformations upon binding to GTP or guanosine diphosphate, and that the Parkinson's disease (PD)-associated R1441C/G/H mutations impair the G-domain monomer-dimer dynamics and trap the G-domain in a constitutive monomeric conformation. That led us to question whether other disease-associated mutations in G-domain would also affect its conformation. Here, we report that another PD-associated N1437H mutation also impairs its monomer-dimer conformational dynamics and GTPase activity. In contrast with mutations at R1441, ROCN1437H was found to be locked in a stable dimeric conformation in solution and its GTPase activity was â¼4-fold lower than that of the wild-type. Furthermore, the N1437H mutation reduced the GTP binding affinity by â¼2.5-fold when compared with other pathogenic G-domain mutations. Moreover, ROCN1437H was found to have a slower GTP dissociation rate, indicating that N1437H might interrupt the nucleotide exchange cycle. Taken together, our data support that conformational dynamics is important for LRRK2 GTPase activity and that the N1437H mutation impairs GTPase activity by locking the ROC domain in a persistently dimeric state.-Huang, X., Wu, C., Park, Y., Long, X., Hoang, Q. Q., Liao, J. The Parkinson's disease-associated mutation N1437H impairs conformational dynamics in the G domain of LRRK2.
Subject(s)
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/chemistry , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , Parkinson Disease/genetics , Blotting, Western , Chromatography, Gel , Circular Dichroism , Electrophoresis, Polyacrylamide Gel , GTP Phosphohydrolases/chemistry , GTP Phosphohydrolases/genetics , GTP Phosphohydrolases/metabolism , Humans , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Mutation/genetics , Protein ConformationABSTRACT
The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m2) and cisplatin (30-35 mg/m2 or 40-50 mg/m2) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Lung Neoplasms/drug therapy , Vinorelbine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Humans , Injections , Quality of Life , Randomized Controlled Trials as Topic , Treatment Outcome , Vinorelbine/administration & dosage , Vinorelbine/adverse effectsABSTRACT
MAIN CONCLUSION: The possible molecular mechanisms regulating strawberry fruit ripening were revealed by plant hormone quantification, exogenous hormone application, and RNA-sequencing. Fruit ripening involves a complex interplay among plant hormones. Strawberry is a model for studies on non-climacteric fruit ripening. However, the knowledge on how plant hormones are involved in strawberry ripening is still limited. To understand hormonal actions in the ripening process, we performed genome-wide transcriptome and hormonal analysis for the five major hormones (abscisic acid and catabolites, auxins, cytokinins, gibberellins, and ethylene) in achenes and receptacles (flesh) at different ripening stages of the woodland strawberry Fragaria vesca. Our results demonstrate that the pre-turning stage (a stage with white flesh and red achenes defined in this study) is the transition stage from immature to ripe fruits. The combinatorial analyses of hormone content, transcriptome data, and exogenous hormone treatment indicate that auxin is synthesized predominantly in achenes, while abscisic acid (ABA), bioactive free base cytokinins, gibberellins, and ethylene are mainly produced in receptacles. Furthermore, gibberellin may delay ripening, while ethylene and cytokinin are likely involved at later stages of the ripening process. Our results also provide additional evidence that ABA promotes ripening, while auxin delays it. Although our hormone analysis demonstrates that the total auxin in receptacles remains relatively low and unchanged during ripening, our experimental evidence further indicates that ABA likely enhances expression of the endoplasmic reticulum-localized auxin efflux carrier PIN-LIKES, which may subsequently reduce the auxin level in nucleus. This study provides a global picture for hormonal regulation of non-climacteric strawberry fruit ripening and also evidence for a possible mechanism of ABA and auxin interaction in the ripening process.
Subject(s)
Fragaria/genetics , Gene Expression Regulation, Plant , Plant Growth Regulators/metabolism , Plant Proteins/metabolism , Transcriptome , Abscisic Acid/analysis , Abscisic Acid/metabolism , Cytokinins/analysis , Cytokinins/metabolism , Ethylenes/analysis , Ethylenes/metabolism , Fragaria/physiology , Fruit/genetics , Fruit/physiology , Gibberellins/analysis , Gibberellins/metabolism , Indoleacetic Acids/analysis , Indoleacetic Acids/metabolism , Plant Growth Regulators/analysis , Plant Proteins/geneticsABSTRACT
It is shown that metallothionein-stabilized copper nanoclusters (MT-CuNCs) display catalase-like activity. In the presence of either lead(II) or mercury(II), the catalase-like activity is converted to a peroxidase-like activity. On addition of Pb(II) or Hg(II), the inhibitory effect of MT-CuNCs on the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB) with H2O2 is weakened. On the other hand, the catalytic effect of the nanoclusters on the chromogenic reaction is increased. The system MT-CuNCs-Pb(II)/Hg(II) exhibits high affinity for the substrates TMB and H2O2. Their catalytic behavior follows Michaelis-Menten kinetics. Based on these findings, a method was developed for visual detection (via the blue coloration formed) and spectrophotometric determination (at 450 nm) of Pb(II) and Hg(II). The linear range for Pb(II) extends from 0.7 to 96 µM, and the linear ranges for Hg(II) from 97 nM to 2.3 µM and from 3.1 µM to 15.6 µM. The detection limits are 142 nM for Pb(II) and 43.8 nM for Hg(II). Graphical abstract Metallothionein-stabilized copper nanoclusters (MT-CuNCs) display catalase-like activity. On addition of Pb(II) or Hg(II), the catalase-like activity is converted to a peroxidase-like activity. The latter catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2.
Subject(s)
Colorimetry/methods , Copper/chemistry , Lead/analysis , Mercury/analysis , Metal Nanoparticles/chemistry , Metallothionein/chemistry , Benzidines/chemistry , Catalysis , Chromogenic Compounds/chemistry , Hydrogen Peroxide/chemistry , Kinetics , Limit of Detection , Spectrometry, Fluorescence/methodsABSTRACT
During male gametogenesis in cereals, the generative cell undergoes a positioning process that parallels the dynamics of the central vacuole, which is believed to be associated with generative cell movement in the male gametophyte. However, the impact of the generative cell positioning and the central vacuole dynamics on male gametogenesis has remained poorly understood. Here, we report that OsGCD1 (GAMETE CELLS DEFECTIVE1) dysfunction influenced pollen development and disrupted pollen germination. Loss of function of OsGCD1 altered the central vacuole dynamics and the generative cell was mispositioned. Nevertheless, twin sperm cells were generated normally, indicating that gametogenesis does not rely on positional information as long as a generative cell is produced. The normal vacuole dynamics seems necessary only for pollen maturation and germination. Our findings also indicate that osgcd1 mutation resulted in rice male sterility in which pollen has full cell viability and generated normal gametes, but lacks the potential to germinate.
Subject(s)
Gametogenesis/physiology , Oryza/physiology , Pollen/physiology , Vacuoles/metabolism , Germination , Mutation/genetics , Plant Proteins/metabolismABSTRACT
Chemical composition of secondary metabolites is of great importance for quality control of agricultural products. Black sesame seeds are significantly more expensive than white sesame seeds, because it is thought that black sesame seeds are more beneficial to human health than white sesame seeds. However, the differences in nutrient composition between black sesame seeds and white sesame seeds are still unknown. The current study examined the levels of different metabolites in black and white sesame seeds via the use of a novel metabolomics strategy. Using widely targeted metabolomics data, we obtained the structure and content of 557 metabolites, out of which 217 metabolites were identified, and discovered 30 metabolic pathways activated by the secondary metabolites in both black and white sesame seeds. Our results demonstrated that the main pathways that were differentially activated included: phenylpropanoid biosynthesis, tyrosine metabolism, and riboflavin metabolism. More importantly, the biomarkers that were significantly different between black seeds and white sesame seeds are highly related to the functions recorded in traditional Chinese medicine. The results of this study may serve as a new theoretical reference for breeding experts to promote the genetic improvement of sesame seeds, and therefore the cultivation of higher quality sesame varieties.
Subject(s)
Metabolome , Metabolomics , Nutrition Assessment , Sesamum/anatomy & histology , Sesamum/metabolism , Chromatography, Liquid , Humans , Medicine, Chinese Traditional , Metabolomics/methods , Seeds/anatomy & histology , Seeds/metabolism , Tandem Mass SpectrometryABSTRACT
Rice fertility is critical for rice reproduction and is thus a focus of interest. Most studies have addressed male sterility and its relation to rice production. The mechanisms of regulation of embryogenesis and endosperm development are essential for rice reproduction, but remain largely unknown. Here, we report a functional analysis of the rice gene OsGCD1, which encodes a highly conserved homolog of Arabidopsis GCD1 (GAMETE CELLS DEFECTIVE1). OsGCD1 mutants were generated using the CRISPR/Cas9 system and subjected to functional analysis. The homozygote mutants cannot be obtained, whereas heterozygotes showed altered phenotypes. In the majority of aborted seeds, the endosperm nucleus divided a limited number of times. The free nuclei were distributed only at the micropylar end of embryo sacs, and their oriented positioning was blocked. In addition, aleurone differentiation was interrupted. The embryo developed slowly, and pattern formation, particularly the dorsal-ventral pattern and symmetry establishment, of embryos was disturbed. Thus, the embryos showed various morphological and structural dysplasias. Our findings reveal that OsGCD1 is essential for rice fertility and is required for dorsal-ventral pattern formation and endosperm free nucleus positioning, suggesting a critical role in sexual reproduction of both monocotyledon and dicotyledon plants.
Subject(s)
Body Patterning , Endosperm/embryology , Endosperm/metabolism , Oryza/embryology , Oryza/physiology , Plant Proteins/metabolism , Amino Acid Sequence , Apoptosis/genetics , Base Sequence , CRISPR-Cas Systems/genetics , Cloning, Molecular , Fertility , Gene Expression Regulation, Developmental , Gene Expression Regulation, Plant , Genes, Plant , Mutagenesis/genetics , Mutation/genetics , Oryza/genetics , Plant Proteins/chemistry , Plant Proteins/genetics , Sequence Analysis, DNAABSTRACT
We previously reported that a novel motor protein belonging to the kinesin-12 family, NtKRP, displays critical roles in regulating embryo and seed size establishment. However, it remains unknown exactly how NtKRP contributes to this developmental process. Here, we report that a 60S ribosomal protein NtRPL17 directly interacts with NtKRP. The phenotypes of NtRPL17 RNAi lines show notable embryo and seed size reduction. Structural observations of the NtRPL17-silenced embryos/seeds reveal that the embryo size reduction is due to a decrease in cell number. In these embryos, cell division cycle progression is delayed at the G2/M transition. These phenotypes are similar to that in NtKRP-silenced embryos/seeds, indicating that NtKRP and NtRPL17 function as partners in the same regulatory pathway during seed development and specifically regulate cell cycle progression to control embryo/seed size. This work reveals that NtRPL17, as a widely distributed ribosomal protein, plays a critical role in seed development and provides a new clue in the regulation of seed size. Confirmation of the interaction between NtKRP and NtRPL17 and their co-function in the control of the cell cycle also suggests that the mechanism might be conserved in both plants and animals.
Subject(s)
Kinesins/genetics , Nicotiana/growth & development , Nicotiana/genetics , Plant Proteins/genetics , Ribosomal Proteins/genetics , Kinesins/metabolism , Plant Proteins/metabolism , Ribosomal Proteins/metabolism , Seedlings/genetics , Seedlings/growth & development , Seeds/genetics , Seeds/growth & development , Nicotiana/metabolismABSTRACT
Plant embryogenesis begins with an asymmetric division of the zygote, producing apical and basal cells with distinct cell fates. The asymmetric zygote division is thought to be critical for embryo pattern formation; however, the molecular mechanisms regulating this process, especially maintaining the accurate position and proper orientation of cell division plane, remain poorly understood. Here, we report that a dynamin-related protein in Nicotiana tabacum, NtDRP, plays a critical role in maintaining orientation of zygotic division plane. Down-regulation of NtDRP caused zygotic cell division to occur in different, incorrect orientations and resulted in disruption of suspensor formation, and even development of twin embryos. The basal cell lineage totally integrated with the apical cell lineage into an embryo-like structure, suggesting that NtDRP is essential to accurate zygotic division orientation and differentiation of basal cell lineage toward suspensor formation. We also reveal that NtDRP plays its role by modulating microtubule spatial organization and spindle orientation during early embryogenesis. Thus, we revealed that NtDRP is involved in orientation of the asymmetric zygotic division and differentiation of distinct suspensor and embryo domains, as well as subsequent embryo pattern formation.