Marginal zone lymphoma with severe rashes: A case report.

BACKGROUND: Marginal zone lymphoma (MZL) is an indolent subtype of non-Hodgkin lymphoma (NHL), which is rare clinically with severe rashes as the initial symptom. CASE SUMMARY: This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge. First-line treatment with rituximab combined with zanubrutinib had poor effects. However, after switching to obinutuzumab combined with zanubrutinib, the case was alleviated, and the rashes disappeared. CONCLUSION: For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody (mAb) combination therapy, switching to a type II anti-CD20 mAb combination regimen may be considered. This approach may provide a new perspective in the treatment of MZL.

A Novel Low Molecule Peptides-calcium Chelate from Silkworm Pupae Protein Hydrolysate: Preparation, Antioxidant Activity, and Bioavailability.

BACKGROUND: The antioxidant properties of active peptides from silkworm pupae protein hydrolysate are of interest, and it serves as a novel source of calcium supplement. METHODS: Optimize the preparation parameters of silkworm pupae bioactive peptide-calcium chelate, and investigate the mechanism and bioavailability of silkworm pupae active peptide as a transport carrier to promote calcium ion absorption using simulated gastrointestinal digestion and Caco-2 monolayer cell model. RESULTS: The optimal process parameters for preparing peptide calcium chelate were the peptide calcium mass ratio of 3:1, pH of 6.7, a temperature of 35.6°C, and time of 32.8 min by Box-Behnken design, and the calciumchelating rate reached 84.67%. The DPPH radical scavenging activity of silkworm pupae protein hydrolysatecalcium chelate was 79.36 ± 4.31%, significantly higher than silkworm pupae protein hydrolysate (61.00 ± 9.56%). Fourier transform infrared spectroscopy shows that the COO-, N-H, C-H, and C-O groups participated in the formation of silkworm pupae protein hydrolysate-calcium chelate. The particle size of the silkworm pupae protein hydrolysate-calcium chelate was 970.75 ± 30.12 nm, which was significantly higher than that of silkworm pupae protein hydrolysate (253.14 ± 5.72 nm). The silkworm pupae protein hydrolysate-calcium chelate showed a calcium dissolution rate of 71.01 ± 1.91% in the simulated intestinal phase, significantly higher than that of CaCl2 (59.34 ± 1.24%). In the Caco-2 cell monolayers, the silkworm pupae protein hydrolysatecalcium chelate was more favorable for calcium transport. CONCLUSION: A novel silkworm pupa protein hydrolysate-calcium chelate with high antioxidant activity was successfully prepared to improve the bioavailability of calcium.

Histidine kinase MHZ1/OsHK1 interacts with ethylene receptors to regulate root growth in rice.

Ethylene plays essential roles during adaptive responses to water-saturating environments in rice, but knowledge of its signaling mechanism remains limited. Here, through an analysis of a rice ethylene-response mutant mhz1, we show that MHZ1 positively modulates root ethylene responses. MHZ1 encodes the rice histidine kinase OsHK1. MHZ1/OsHK1 is autophosphorylated at a conserved histidine residue and can transfer the phosphoryl signal to the response regulator OsRR21 via the phosphotransfer proteins OsAHP1/2. This phosphorelay pathway is required for root ethylene responses. Ethylene receptor OsERS2, via its GAF domain, physically interacts with MHZ1/OsHK1 and inhibits its kinase activity. Genetic analyses suggest that MHZ1/OsHK1 acts at the level of ethylene perception and works together with the OsEIN2-mediated pathway to regulate root growth. Our results suggest that MHZ1/OsHK1 mediates the ethylene response partially independently of OsEIN2, and is directly inhibited by ethylene receptors, thus revealing mechanistic details of ethylene signaling for root growth regulation.

E3 ubiquitin ligase SOR1 regulates ethylene response in rice root by modulating stability of Aux/IAA protein.

Plant hormones ethylene and auxin synergistically regulate plant root growth and development. Ubiquitin-mediated proteolysis of Aux/IAA transcriptional repressors by the E3 ubiquitin ligase SCFTIR1/AFB triggers a transcription-based auxin signaling. Here we show that rice (Oryza sativa L.) soil-surface rooting 1 (SOR1), which is a RING finger E3 ubiquitin ligase identified from analysis of a rice ethylene-insensitive mutant mhz2/sor1-2, controls root-specific ethylene responses by modulating Aux/IAA protein stability. SOR1 physically interacts with OsIAA26 and OsIAA9, which are atypical and canonical Aux/IAA proteins, respectively. SOR1 targets OsIAA26 for ubiquitin/26S proteasome-mediated degradation, whereas OsIAA9 protects the OsIAA26 protein from degradation by inhibiting the E3 activity of SOR1. Auxin promotes SOR1-dependent degradation of OsIAA26 by facilitating SCFOsTIR1/AFB2-mediated and SOR1-assisted destabilization of OsIAA9 protein. Our study provides a candidate mechanism by which the SOR1-OsIAA26 module acts downstream of the OsTIR1/AFB2-auxin-OsIAA9 signaling to modulate ethylene inhibition of root growth in rice seedlings.

Ethylene-Inhibited Jasmonic Acid Biosynthesis Promotes Mesocotyl/Coleoptile Elongation of Etiolated Rice Seedlings.

Elongation of the mesocotyl and coleoptile facilitates the emergence of rice (Oryza sativa) seedlings from soil and is affected by various genetic and environment factors. The regulatory mechanism underlying this process remains largely unclear. Here, we examined the regulation of mesocotyl and coleoptile growth by characterizing a gaoyao1 (gy1) mutant that exhibits a longer mesocotyl and longer coleoptile than its original variety of rice. GY1 was identified through map-based cloning and encodes a PLA1-type phospholipase that localizes in chloroplasts. GY1 functions at the initial step of jasmonic acid (JA) biosynthesis to repress mesocotyl and coleoptile elongation in etiolated rice seedlings. Ethylene inhibits the expression of GY1 and other genes in the JA biosynthesis pathway to reduce JA levels and enhance mesocotyl and coleoptile growth by promoting cell elongation. Genetically, GY1 acts downstream of the OsEIN2-mediated ethylene signaling pathway to regulate mesocotyl/coleoptile growth. Through analysis of the resequencing data from 3000 rice accessions, we identified a single natural variation of the GY1 gene, GY1376T , which contributes to mesocotyl elongation in rice varieties. Our study reveals novel insights into the regulatory mechanism of mesocotyl/coleoptile elongation and should have practical applications in rice breeding programs.

MAOHUZI6/ETHYLENE INSENSITIVE3-LIKE1 and ETHYLENE INSENSITIVE3-LIKE2 Regulate Ethylene Response of Roots and Coleoptiles and Negatively Affect Salt Tolerance in Rice.

Ethylene plays important roles in plant growth, development, and stress responses. The ethylene signaling pathway has been studied extensively, mainly in Arabidopsis (Arabidopsis thaliana). However, the molecular mechanism of ethylene signaling is largely unknown in rice (Oryza sativa). Previously, we have isolated a set of rice ethylene-response mutants. Here, we characterized the mutant maohuzi6 (mhz6). Through map-based cloning, we found that MHZ6 encodes ETHYLENE INSENSITIVE3-LIKE1 (OsEIL1), a rice homolog of ETHYLENE INSENSITIVE3 (EIN3), which is the master transcriptional regulator of ethylene signaling in Arabidopsis. Disruption of MHZ6/OsEIL1 caused ethylene insensitivity mainly in roots, whereas silencing of the closely related OsEIL2 led to ethylene insensitivity mainly in coleoptiles of etiolated seedlings. This organ-specific functional divergence is different from the functional features of EIN3 and EIL1, both of which mediate the incomplete ethylene responses of Arabidopsis etiolated seedlings. In Arabidopsis, EIN3 and EIL1 play positive roles in plant salt tolerance. In rice, however, lack of MHZ6/OsEIL1 or OsEIL2 functions improves salt tolerance, whereas the overexpressing lines exhibit salt hypersensitivity at the seedling stage, indicating that MHZ6/OsEIL1 and OsEIL2 negatively regulate salt tolerance in rice. Furthermore, this negative regulation by MHZ6/OsEIL1 and OsEIL2 in salt tolerance is likely attributable in part to the direct regulation of HIGH-AFFINITY K(+) TRANSPORTER2;1 expression and Na(+) uptake in roots. Additionally, MHZ6/OsEIL1 overexpression promotes grain size and thousand-grain weight. Together, our study provides insights for the functional diversification of MHZ6/OsEIL1 and OsEIL2 in ethylene response and finds a novel mode of ethylene-regulated salt stress response that could be helpful for engineering salt-tolerant crops.

Ethylene responses in rice roots and coleoptiles are differentially regulated by a carotenoid isomerase-mediated abscisic acid pathway.

Ethylene and abscisic acid (ABA) act synergistically or antagonistically to regulate plant growth and development. ABA is derived from the carotenoid biosynthesis pathway. Here, we analyzed the interplay among ethylene, carotenoid biogenesis, and ABA in rice (Oryza sativa) using the rice ethylene response mutant mhz5, which displays a reduced ethylene response in roots but an enhanced ethylene response in coleoptiles. We found that MHZ5 encodes a carotenoid isomerase and that the mutation in mhz5 blocks carotenoid biosynthesis, reduces ABA accumulation, and promotes ethylene production in etiolated seedlings. ABA can largely rescue the ethylene response of the mhz5 mutant. Ethylene induces MHZ5 expression, the production of neoxanthin, an ABA biosynthesis precursor, and ABA accumulation in roots. MHZ5 overexpression results in enhanced ethylene sensitivity in roots and reduced ethylene sensitivity in coleoptiles. Mutation or overexpression of MHZ5 also alters the expression of ethylene-responsive genes. Genetic studies revealed that the MHZ5-mediated ABA pathway acts downstream of ethylene signaling to inhibit root growth. The MHZ5-mediated ABA pathway likely acts upstream but negatively regulates ethylene signaling to control coleoptile growth. Our study reveals novel interactions among ethylene, carotenogenesis, and ABA and provides insight into improvements in agronomic traits and adaptive growth through the manipulation of these pathways in rice.

Ethylene-induced inhibition of root growth requires abscisic acid function in rice (Oryza sativa L.) seedlings.

Ethylene and abscisic acid (ABA) have a complicated interplay in many developmental processes. Their interaction in rice is largely unclear. Here, we characterized a rice ethylene-response mutant mhz4, which exhibited reduced ethylene-response in roots but enhanced ethylene-response in coleoptiles of etiolated seedlings. MHZ4 was identified through map-based cloning and encoded a chloroplast-localized membrane protein homologous to Arabidopsis thaliana (Arabidopsis) ABA4, which is responsible for a branch of ABA biosynthesis. MHZ4 mutation reduced ABA level, but promoted ethylene production. Ethylene induced MHZ4 expression and promoted ABA accumulation in roots. MHZ4 overexpression resulted in enhanced and reduced ethylene response in roots and coleoptiles, respectively. In root, MHZ4-dependent ABA pathway acts at or downstream of ethylene receptors and positively regulates root ethylene response. This ethylene-ABA interaction mode is different from that reported in Arabidopsis, where ethylene-mediated root inhibition is independent of ABA function. In coleoptile, MHZ4-dependent ABA pathway acts at or upstream of OsEIN2 to negatively regulate coleoptile ethylene response, possibly by affecting OsEIN2 expression. At mature stage, mhz4 mutation affects branching and adventitious root formation on stem nodes of higher positions, as well as yield-related traits. Together, our findings reveal a novel mode of interplay between ethylene and ABA in control of rice growth and development.

Identification of rice ethylene-response mutants and characterization of MHZ7/OsEIN2 in distinct ethylene response and yield trait regulation.

Ethylene plays essential roles in adaptive growth of rice plants in water-saturating environment; however, ethylene signaling pathway in rice is largely unclear. In this study, we report identification and characterization of ethylene-response mutants based on the specific ethylene-response phenotypes of etiolated rice seedlings, including ethylene-inhibited root growth and ethylene-promoted coleoptile elongation, which is different from the ethylene triple-response phenotype in Arabidopsis. We establish an efficient system for screening and a set of rice mutants have been identified. Genetic analysis reveals that these mutants form eight complementation groups. All the mutants show insensitivity or reduced sensitivity to ethylene in root growth but exhibit differential responses in coleoptile growth. One mutant group mhz7 has insensitivity to ethylene in both root and coleoptile growth. We identified the corresponding gene by a map-based cloning method. MHZ7 encodes a membrane protein homologous to EIN2, a central component of ethylene signaling in Arabidopsis. Upon ethylene treatment, etiolated MHZ7-overexpressing seedlings exhibit enhanced coleoptile elongation, increased mesocotyl growth and extremely twisted short roots, featuring enhanced ethylene-response phenotypes in rice. Grain length was promoted in MHZ7-transgenic plants and 1000-grain weight was reduced in mhz7 mutants. Leaf senescent process was also affected by MHZ7 expression. Manipulation of ethylene signaling may improve adaptive growth and yield-related traits in rice.

The ethylene receptor ETR2 delays floral transition and affects starch accumulation in rice.

Ethylene regulates multiple aspects of plant growth and development in dicotyledonous plants; however, its roles in monocotyledonous plants are poorly known. Here, we characterized a subfamily II ethylene receptor, ETHYLENE RESPONSE2 (ETR2), in rice (Oryza sativa). The ETR2 receptor with a diverged His kinase domain is a Ser/Thr kinase, but not a His kinase, and can phosphorylate its receiver domain. Mutation of the N box of the kinase domain abolished the kinase activity of ETR2. Overexpression of ETR2 in transgenic rice plants reduced ethylene sensitivity and delayed floral transition. Conversely, RNA interference (RNAi) plants exhibited early flowering and the ETR2 T-DNA insertion mutant etr2 showed enhanced ethylene sensitivity and early flowering. The effective panicles and seed-setting rate were reduced in the ETR2-overexpressing plants, while thousand-seed weight was substantially enhanced in both the ETR2-RNAi plants and the etr2 mutant compared with controls. Starch granules accumulated in the internodes of the ETR2-overexpressing plants, but not in the etr2 mutant. The GIGANTEA and TERMINAL FLOWER1/CENTRORADIALIS homolog (RCN1) that cause delayed flowering were upregulated in ETR2-overexpressing plants but downregulated in the etr2 mutant. Conversely, the alpha-amylase gene RAmy3D was suppressed in ETR2-overexpressing plants but enhanced in the etr2 mutant. Thus, ETR2 may delay flowering and cause starch accumulation in stems by regulating downstream genes.

Characterization of an NBS-LRR resistance gene homologue from soybean.

Conserved motifs such as the nucleotide-binding site (NBS) were found in many characterized plant disease resistance genes. Based on the NBS domain, resistance gene analogs have been isolated in our previous study and were used as probes to screen a soybean (Glycine max) cDNA library. A full-length cDNA, KR4, was isolated by screening the library and rapid amplification of cDNA ends method. Sequence analysis revealed that the cDNA was 3818 bp in length and the open reading frame coded for a polypeptide of 1211 amino acids with an NBS and five leucine-rich repeats domains, which were identified by Pfam protein analysis. Sequence alignment showed that KR4 was similar to 12 protein of tomato. Southern analysis indicated that the KR4 gene had low copies in soybean genome and it was mapped on the molecular linkage group E. Its expression was also investigated and it was found that KR4 was induced by exogenous salicylic acid and responded upon infection of soybean mosaic virus strain N3.

Spatial expression and characterization of a putative ethylene receptor protein NTHK1 in tobacco.

A putative ethylene receptor gene NTHK1 encodes a protein with a putative signal peptide, three transmembrane segments, a putative histidine kinase domain and a putative receiver domain. The receiver domain was expressed in an Escherichia coli expression system, purified and used to generate polyclonal antibodies for immunohistochemistry analysis. The spatial expression of the NTHK1 protein was then investigated. We found that NTHK1 was abundant during flower and ovule development. It was also expressed in glandular hairs, stem, and in leaves that had been wounded. The NTHK1 gene was further introduced into the tobacco plant and we found that, in different transgenic lines, the NTHK1 gene was transcribed to various degrees. Upon ACC treatment, the etiolated transgenic seedlings showed reduced ethylene sensitivity when compared with the control, indicating that NTHK1 is a functional ethylene receptor in plants.