A novel OsGST gene encoding 9glutathione reductase negatively regulates cadmium accumulation in rice.

Cadmium (Cd) accumulates in rice and then moves up the food chain, causing serious health problems for humans. Glutathione S-transferase (GST) binds exogenous hazardous compounds to glutathione (GSH), which performs a variety of roles in plant responses to Cd stress. Here, Cd stimulated the transcripts of a novel OsGST gene, and the OsGST protein, which was localized in the nucleus and cytoplasm, was also induced by Cd. In OsGST deletion mutant lines generated by CRISPR/Cas9, more Cd was accumulated, and Cd hypersensitive phenotypes were observed, while transgenic lines overexpressing OsGST exhibited enhanced Cd tolerance and less Cd accumulation. Further analysis indicated that the osgst mutants exhibited considerably greater reactive oxygen species (ROS) and higher GSH level, and the antioxidant activity associated genes' expression were down-regulated, imply that OsGST controlled rice Cd accumulation and resistance through preserving the equilibrium of the GSH and redox in rice.

Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents.

Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)2PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through 1H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)2PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of 1H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by 31P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (Rs)". Significantly, this class of CSAs based on (alkaloid)2linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.

A NAC transcription factor represses a module associated with xyloglucan content and regulates aluminum tolerance.

The transcriptional regulation of aluminum (Al) tolerance in plants is largely unknown, although Al toxicity restricts agricultural yields in acidic soils.. Here, we identified a NAM, ATAF1/2, and cup-shaped cotyledon 2 (NAC) transcription factor that participates in Al tolerance in Arabidopsis (Arabidopsis thaliana). Al substantially induced the transcript and protein levels of ANAC070, and loss-of-function anan070 mutants showed remarkably increased Al sensitivity, implying a beneficial role of ANAC070 in plant tolerance to Al toxicity. Further investigation revealed that more Al accumulated in the roots of anac070 mutants, especially in root cell walls, accompanied by a higher hemicellulose and xyloglucan level, implying a possible interaction between ANAC070 and genes that encode proteins responsible for the modification of xyloglucan, including xyloglucan endo-transglycosylases/hydrolase (XTH) or ANAC017. Yeast one hybrid analysis revealed a potential interaction between ANAC070 and ANAC017, but not for other XTHs. Furthermore, dual-luciferase reporter assay, RT-qPCR, and GUS analysis revealed that ANAC070 could directly repress the transcript levels of ANAC017, and knockout of ANAC017 in the anac070 mutant partially restored its Al sensitivity phenotype, indicating that ANAC070 contributes to Al tolerance mechanisms other than suppression of ANAC017 expression. Further analysis revealed that the core transcription factor SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1) and its target genes, which control Al tolerance in Arabidopsis, may also be involved in ANAC070-regulated Al tolerance. In summary, we identified a transcription factor, ANAC070, that represses the ANAC017-XTH31 module to regulate Al tolerance in Arabidopsis.

A novel aldo-keto reductase gene, OsAKR1, from rice confers higher tolerance to cadmium stress in rice by an in vivo reactive aldehyde detoxification.

Elevated levels of cadmium (Cd) have the ability to impede plant development. Aldo-keto reductases (AKRs) have been demonstrated in a number of plant species to improve tolerance to a variety of abiotic stresses by scavenging cytotoxic aldehydes; however, only a few AKRs have been identified to improve Cd tolerance. The OsAKR1 gene was extracted and identified from rice here. After being exposed to Cd, the expression of OsAKR1 dramatically rose in both roots and shoots, although more pronounced in roots. According to a subcellular localization experiment, the nucleus and cytoplasm are where OsAKR1 is primarily found. Mutants lacking OsAKR1 exhibited Cd sensitive phenotype than that of the wild-type (WT) Nipponbare (Nip), and osakr1 mutants exhibited reduced capacity to scavenge methylglyoxal (MG). Furthermore, osakr1 mutants exhibited considerably greater hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels, and increased catalase (CAT) activity in comparison to Nip. The expression of three isomeric forms of CAT was found to be considerably elevated in osakr1 mutants during Cd stress, as demonstrated by quantitative real-time PCR analysis, when compared to Nip. These results imply that OsAKR1 controlled rice's ability to withstand Cd by scavenging harmful aldehydes and turning on the reactive oxygen species (ROS) scavenging mechanism.

Brassinosteroid decreases cadmium accumulation via regulating gibberellic acid accumulation and Cd fixation capacity of root cell wall in rice (Oryza sativa).

The precise mechanism behind the association between plants' reactions to cadmium (Cd) stress and brassinosteroid (BR) remains unclear. In the current investigation, Cd stress quickly increased the endogenous BR concentration in the rice roots. Exogenous BR also increased the hemicellulose level in the root cell wall, which in turn increased its capacity to bind Cd. Simultaneously, the transcription level of genes responsible for root Cd absorption was decreased, including Natural Resistance-Associated Macrophage Protein 1/5 (OsNRAMP1/5) and a major facilitator superfamily gene called OsCd1. Ultimately, the increased expression of Heavy Metal ATPase 3 (OsHMA3) and the decreased expression of OsHMA2, which was in charge of separating Cd into vacuoles and translocating Cd to the shoots, respectively, led to a decrease in the amount of Cd that accumulated in the rice shoots. In contrast, transgenic rice lines overexpressing OsGSK2 (a negative regulator in BR signaling) accumulated more Cd, while OsGSK2 RNA interference (RNAi) rice line accumulated less Cd. Furthermore, BR increased endogenous Gibberellic acid (GA) level, and applying GA could replicate its alleviative effect. Taken together, BR decreased Cd accumulation in rice by mediating the cell wall's fixation capacity to Cd, which might relied on the buildup of the GA.

Genetic control of DNA methylation is largely shared across European and East Asian populations.

DNA methylation is an ideal trait to study the extent of the shared genetic control across ancestries, effectively providing hundreds of thousands of model molecular traits with large QTL effect sizes. We investigate cis DNAm QTLs in three European (n = 3701) and two East Asian (n = 2099) cohorts to quantify the similarities and differences in the genetic architecture across populations. We observe 80,394 associated mQTLs (62.2% of DNAm probes with significant mQTL) to be significant in both ancestries, while 28,925 mQTLs (22.4%) are identified in only a single ancestry. mQTL effect sizes are highly conserved across populations, with differences in mQTL discovery likely due to differences in allele frequency of associated variants and differing linkage disequilibrium between causal variants and assayed SNPs. This study highlights the overall similarity of genetic control across ancestries and the value of ancestral diversity in increasing the power to detect associations and enhancing fine mapping resolution.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Auxin acts upstream of nitric oxide to regulate cell wall xyloglucan and its aluminium-binding capacity in Arabidopsis thaliana.

MAIN CONCLUSION: Auxin acts upstream of NO through NOA and XXT5 pathways to regulate the binding capacity of the root cell wall to Al. In our previous study, we identified an unknown mechanism by which 1-naphthaleneacetic acid (NAA) decreased the fixation of aluminum (Al) in the cell wall. Here, we observed that external application of the nitric oxide (NO) donor S-nitrosoglutathion (GSNO) increased the inhibition of Al on root elongation. Further analysis indicated that GSNO could induce Al accumulation in the roots and root cell walls, which is consistent with lower xyloglucan content. In comparison to the Columbia-0 (Col-0) wild type (WT), endogenous NO-reduced mutants noa1 (NOA pathway) and nia1nia2 (NR pathway) were more resistant to Al, with lower root Al content, higher xyloglucan content, and more Al accumulation in the root cell walls. By contrast, the xxt5 mutant with reduced xyloglucan content exhibited an Al-sensitive phenotype. Interestingly, Al treatment increased the endogenous auxin and NO levels, and the auxin levels induced under Al stress further stimulated NO production. Auxin application reduced Al retention in hemicellulose and decreased the xyloglucan content, similar to the effects observed with GSNO. In yucca and aux1-7 mutants, exogenous application of NO resulted in responses similar to those of the WT, whereas exogenous auxin had little effect on the noa1 mutant under Al stress. In addition, as auxin had similar effects on the nia1nia2 mutant and the WT, exogenous auxin and NO had little effect on the xxt5 mutant under Al stress, further confirming that auxin acts upstream of NO through NOA and XXT5 pathways to regulate the binding capacity of the root cell wall to Al.

Exome sequencing in retinal dystrophy patients reveals a novel candidate gene ER membrane protein complex subunit 3.

Inherited retinal dystrophies (IRDs) are a heterogeneous group of visual disorders caused by different pathogenic mutations in genes and regulatory sequences. The endoplasmic reticulum (ER) membrane protein complex (EMC) subunit 3 (EMC3) is the core unit of the EMC insertase that integrates the transmembrane peptides into lipid bilayers, and the function of its cytoplasmic carboxyl terminus remains to be elucidated. In this study, an insertional mutation c.768insT in the C-terminal coding region of EMC3 was identified and associated with dominant IRDs in a five-generation family. This mutation caused a frameshift in the coding sequence and a gain of an additional 16 amino acid residues (p.L256F-fs-ext21) to form a helix structure in the C-terminus of the EMC3 protein. The mutation is heterozygous with an incomplete penetrance, and cosegregates in all patients examined. This finding indicates that the C-terminus of EMC3 is essential for EMC functions and that EMC3 may be a novel candidate gene for retinal degenerative diseases.

Auxin is involved in cadmium accumulation in rice through controlling nitric oxide production and the ability of cell walls to bind cadmium.

Although auxin has been linked to plants' responses to cadmium (Cd) stress, the exact mechanism is yet elusive. The objective of the current investigation was to determine the role and the mechanism of auxin in controlling rice's Cd accumulation. Rice roots with Cd stress have higher endogenous auxin levels, and exogenous auxin combined Cd treatment could reduce root cell wall's hemicellulose content when compared with Cd treatment alone, which in turn reduced its fixation of Cd, as well as decreased the expression of OsCd1 (a major facilitator superfamily gene), OsNRAMP1/5 (Natural Resistance-Associated Macrophage Protein 1/5), OsZIP5/9 (Zinc Transporter 5/9), and OsHMA2 (Heavy Metal ATPase 2) that participated in Cd uptake and root to shoot translocation. Furthermore, less Cd accumulated in the shoots as a result of auxin's impact in increasing the expression of OsCAL1 (Cadmium accumulation in Leaf 1), OsABCG36/OsPDR9 (G-type ATP-binding cassette transporter/Pleiotropic drug resistance 9), and OsHMA3, which were in charge of Cd efflux and sequestering into vacuoles, respectively. Additionally, auxin decreased endogenous nitric oxide (NO) levels and antioxidant enzyme activity, while treatment of a NO scavenger-cPTIO-reduced auxin's alleviatory effects. In conclusion, the rice's ability to tolerate Cd toxicity was likely increased by the auxin-accelerated cell wall Cd exclusion mechanism, a pathway that controlled by the buildup of NO.

Salylic acid minimize cadmium accumulation in rice through regulating the fixation capacity of the cell wall to cadmium.

Although salylic acid (SA) has been linked to how plants react to cadmium (Cd) stress, the exact mechanism is still unknown. The endogenous SA concentration in the rice (Oryza sativa L.) roots was enhanced by Cd stress in the current investigation, and exogenous SA reduced the hemicellulose content in root cell wall, which in turn inhibited its Cd binding capacity. What's more, exogenous SA also decreased the transcription level of genes such as Natural Resistance-Associated Macrophage Protein 5 (OsNRAMP5) and a major facilitator superfamily gene-OsCd1 that responsible for root Cd absorption. Finally, less Cd was accumulated in the rice as a result of the higher expression of Heavy Metal ATPase 3 (OsHMA3), Cation/Ca exchanger 2 (OsCCX2) and Pleiotropic Drug Resistance 9 (OsPDR9/OsABCG36) that were responsible for separating Cd into vacuole and getting Cd out of cells, respectively. In contrast, mutant with low SA level accumulated more Cd. Additionally, SA enhanced endogenous nitric oxide (NO) levels, and its alleviatory effects were mimicked by a NO donor, sodium nitroprusside (SNP). In conclusion, SA enhanced rice's Cd resistance through regulating the binding capacity of the cell wall to Cd, a pathway that might dependent on the NO accumulation.

A dual nociceptin and mu opioid receptor agonist exhibited robust antinociceptive effect with decreased side effects.

The compelling demand of a consummate analgesic medication without addiction is rising due to the clinical mistreatment. Additionally, the series of severe untoward effects usually deterred the utilization while coping with serious pain. As a possible turning point, we revealed that compound 14 is a dual agonist of mu opioid receptor (MOR) and nociceptin-orphanin FQ opioid peptide (NOP) receptor in this study. More importantly, compound 14 achieves pain relieving at very small doses, meanwhile, reduces several unwanted side effects such as constipation, reward, tolerance and withdrawal effects. Here, we evaluated the antinociception and side effects of this novel compound from wild type and humanized mice to further develop a safer prescription analgesic drug.

Detection and discrimination of pathogenic bacteria with nanomaterials-based optical biosensors: A review.

Pathogenic bacteria can pose a great threat to food safety and human health. It is therefore imperative to develop a rapid, portable, and sensitive determination and discrimination method for pathogenic bacteria. Over the past few years, various nanomaterials (NMs) have been employed as desirable nanoprobes because they possess extraordinary properties that can be used for optical signal enabled detection and identification of bacteria. By means of modification, NMs can, depending on different mechanisms, sense targets directly or indirectly, which then provides an essential support for the detection and differentiation of pathogenic bacteria. In this review, recent application of NMs-based optical biosensors for food safety bacterial detection and discrimination is performed, mainly in but not limited to noble metal NMs, fluorescent NMs, and point-of-care testing (POCT). This review also focuses on future trends in bacterial detection and discrimination, and machine learning in performing intelligent rapid detection and multiple accurate identification of bacteria.

Involvement of the 4-coumarate:coenzyme A ligase 4CL4 in rice phosphorus acquisition and rhizosphere microbe recruitment via root growth enlargement.

MAIN CONCLUSION: The 4-coumarate:coenzyme A ligase 4CL4 is involved in enhancing rice P acquisition and use in acid soil by enlarging root growth and boosting functional rhizosphere microbe recruitment. Rice (Oryza sativa L.) cannot easily acquire phosphorus (P) from acid soil, where root growth is inhibited and soil P is fixed. The combination of roots and rhizosphere microbiota is critical for plant P acquisition and soil P mobilization, but the associated molecular mechanism in rice is unclear. 4CL4/RAL1 encodes a 4-coumarate:coenzyme A ligase related to lignin biosynthesis in rice, and its dysfunction results in a small rice root system. In this study, soil culture and hydroponic experiments were conducted to examine the role of RAL1 in regulating rice P acquisition, fertilizer P use, and rhizosphere microbes in acid soil. Disruption of RAL1 markedly decreased root growth. Mutant rice plants exhibited decreased shoot growth, shoot P accumulation, and fertilizer P use efficiency when grown in soil-but not under hydroponic conditions, where all P is soluble and available for plants. Mutant ral1 and wild-type rice rhizospheres had distinct bacterial and fungal community structures, and wild-type rice recruited some genotype-specific microbial taxa associated with P solubilization. Our results highlight the function of 4CL4/RAL1 in enhancing rice P acquisition and use in acid soil, namely by enlarging root growth and boosting functional rhizosphere microbe recruitment. These findings can inform breeding strategies to improve P use efficiency through host genetic manipulation of root growth and rhizosphere microbiota.

The value of bile acid spectrum in the evaluation of hepatic injury in children with infectious mononucleosis caused by Epstein Barr virus infection.

Background: Infectious mononucleosis (IM) is an acute infectious disease, caused by Epstein-Barr virus (EBV) infection, which can invade various systemic systems, among which hepatic injury is the most common. In this study, ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to detect serum bile acid spectrum in IM children quantitatively, and to investigate its role in the early assessment of hepatic injury. Methods: This case-control study was conducted at Yuhuan People's Hospital. A total of 60 IM children and 30 healthy children were included in the study. Among 60 children with IM, 30 had hepatic injury, and 30 without hepatic injury. The clinical and laboratory data were analyzed, and the serum bile acid spectrum and lymphocyte subsets were evaluated in the three groups. Results: There were statistically significant differences in cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid(GDCA), glycolithocholic acid (GLCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA), tauroursodeoxycholic acid(TUDCA), percentage of NK cells, CD4+ and CD8+ in IM hepatic injury group, without hepatic injury group, and the healthy control group (P < 0.05). The percentage of NK cells was positively correlated with TCA (P < 0.05); it was negatively correlated with CDCA, DCA, LCA, GCDCA, GDCA, GLCA, TDCA, UDCA, GUDCA, TUDCA (P < 0.05). CD4+ was positively correlated with CA, TCA and TCDCA (P < 0.05); it was negatively correlated with CDCA, DCA, LCA, GCDCA, GDCA, GLCA, TDCA, UDCA, GUDCA and TUDCA (P < 0.05). CD8+ was positively correlated with CDCA, DCA, LCA, GCDCA, GDCA, GLCA, TDCA, UDCA, GUDCA and TUDCA (P < 0.05); it was negatively correlated with CA, TCA and TCDCA (P < 0.05). ROC curve analysis showed that CD8+, GDCA and GLCA had high predictive value for hepatic injury in IM patients. Conclusions: UPLC-MS/MS method can sensitively detect the changes in serum bile acid spectrum before hepatic injury in children with IM, which is helpful for early assessment of hepatic injury in children with IM. The changes in lymphocyte subsets in IM children are related to some bile acid subfractions, which may be related to IM hepatic injury.

A self-designed device integrated with a Fermat spiral microfluidic chip for ratiometric and automated point-of-care testing of anthrax biomarker in real samples.

A desirable lanthanide-based ratiometric fluorescent probe was designed and integrated into a self-designed Fermat spiral microfluidic chip (FS-MC) for the automated determination of a unique bacterial endospore biomarker, dipicolinic acid (DPA), with high selectivity and sensitivity. Here, a blue emission wavelength at 425 nm was generated in the Fermat spiral structure by mixing the europium (Eu3+) and luminol to form the Eu3+/Luminol sensing probe. DPA in the reservoir can be used to specifically bind to Eu3+ under the negative pressure and transfer energy from DPA to Eu3+ sequentially via an antenna effect, thus resulting in a significant increase in the red fluorescence emission peak at 615 nm. According to the fluorescence intensity ratio (F615/F425), a good linearity can be obtained with increasing the concentration of DPA from 0 to 200 µM with a limit of detection as low as 10.11 nM. Interestingly, the designed FS-MC can achieve rapid detection of DPA in only 1 min, reducing detection time and improving sensitivity. Furthermore, a self-designed device integrated with the FS-MC and a smartphone color picker APP was employed for the rapid automatic point-of-care testing (POCT) of DPA in the field, simplifying complex processes and reducing testing times, thus confirming the great promise of this ready-to-use measurement platform for in situ inspection.

Melatonin reduces cadmium accumulation via mediating the nitric oxide accumulation and increasing the cell wall fixation capacity of cadmium in rice.

Melatonin (MT) is participated in plants' response to cadmium (Cd) tolerance, although its work model remains elusive. Here, the function of MT in adjusting Cd accumulation in rice was investigated. 'Nipponbare' (Nip) was cultured in the -Cd (1/2 Kimura B), -Cd + MT (1/2 Kimura B with 1 µM MT), +Cd (1/2 Kimura B plus 1 µM Cd) and +Cd + MT (1/2 Kimura B with 1 µM Cd and 1 µM MT) nutrient solutions for 7 d. Cd markedly induced the endogenous MT accumulation in rice roots and shoots, even within 1 h. MT applied exogenously elevated the hemicelluloses level, which in turn increased the cell wall's binding capacity to Cd. Furthermore, MT applied exogenously down-regulated the transcription level of Natural Resistance-Associated Macrophage Protein 1 (OsNRAMP1), OsNRAMP5, a major facilitator superfamily gene (OsCd1), and IRON-REGULATED TRANSPORTER 1 (OsIRT1), all of which were responsible for Cd intake, thus less Cd was entered into roots. Moreover, MT applied exogenously also up-regulated transcription level of Cadmium accumulation in Leaf 1 (OsCAL1) and Heavy Metal ATPase 3 (OsHMA3), two genes both attributed to the decreased Cd accumulation in shoots through expelling Cd out of cells and chelating Cd in the vacuoles, respectively. In addition, MT applied exogenously further aggravated the production of nitric oxide (NO) that induced by Cd, while application of a NO donor-SNP mimicked this alleviatory effect of the MT, indicating MT decreased rice Cd accumulation relied on the accumulation of NO.

Acromicric dysplasia caused by a mutation of fibrillin 1 in a family: A case report.

BACKGROUND: Acromicric dysplasia (AD) is a rare skeletal dysplasia. Its incidence is < 1/1000000, and only approximately 60 cases are reported worldwide. It is a disease characterized by severe short stature, short hands and feet, facial abnormalities, normal intelligence, and bone abnormalities. Unlike other skeletal dysplasia, AD has a mild clinical phenotype, mainly characterized by short stature. Extensive endocrine examination has not revealed a potential cause. The clinical effect of growth hormone therapy is still uncertain. CASE SUMMARY: We report a clinical phenotype of AD associated with mutations in the fibrillin 1 (FBN1) (OMIM 102370) gene c.5183C>T (p. Ala1728Val) in three people from a Chinese family. A 4-year-old member of the family first visited the hospital because of slow growth and short stature for 2 years, but no abnormalities were found after a series of laboratory tests, echocardiography, pituitary magnetic resonance imaging, and ophthalmological examination. Recombinant human growth hormone (rhGH) was used to treat the patient for > 5 years. The efficacy of rhGH was apparent in the first year of treatment; the height increased from -3.64 standard deviation score (SDS) to -2.88 SDS, while the efficacy weakened from the second year. However, long-term follow-up is required to clarify the efficacy of rhGH. CONCLUSION: FBN1-related AD has genetic heterogeneity and/or clinical variability, which brings challenges to the evaluation of clinical treatment. rhGH is effective for treatment of AD, but long-term follow-up is needed to clarify the effect.

The endo-beta mannase MAN7 contributes to cadmium tolerance by modulating root cell wall binding capacity in Arabidopsis thaliana.

The heavy metal cadmium (Cd) is detrimental to crop growth and threatens human health through the food chain. To cope with Cd toxicity, plants employ multiple strategies to decrease Cd uptake and its root-to-shoot translocation. However, genes that participate in the Cd-induced transcriptional regulatory network, including those encoding transcription factors, remain largely unidentified. In this study, we demonstrate that ENDO-BETA-MANNASE 7 (MAN7) is necessary for the response of Arabidopsis thaliana to toxic Cd levels. We show that MAN7 is responsible for mannase activity and modulates mannose content in the cell wall, which plays a role in Cd compartmentalization in the cell wall under Cd toxicity conditions. Additionally, the repression of root growth by Cd was partially reversed via exogenous application of mannose, suggesting that MAN7-mediated cell wall Cd redistribution depends on the mannose pathway. Notably, we identified a basic leucine zipper (bZIP) transcription factor, bZIP44, that acts upstream of MAN7 in response to Cd toxicity. Transient dual-luciferase assays indicated that bZIP44 directly binds to the MAN7 promoter region and activates its transcription. Loss of bZIP44 function was associated with greater sensitivity to Cd treatment and higher accumulation of the heavy metal in roots and shoots. Moreover, MAN7 overexpression relieved the inhibition of root elongation seen in the bzip44 mutant under Cd toxicity conditions. This study thus reveals a pathway showing that MAN7-associated Cd tolerance in Arabidopsis is controlled by bZIP44 upon Cd exposure.