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15 pages, 932 KB  
Systematic Review
Androgenetic Alopecia and Risks of Overall and Aggressive Prostate Cancer: An Updated Systematic Review and Meta-Analysis
by David G. Hanelin, Sapir Amar and Ilir Agalliu
Cancers 2025, 17(21), 3581; https://doi.org/10.3390/cancers17213581 - 6 Nov 2025
Viewed by 2495
Abstract
Background: Androgenetic alopecia, also known as male pattern baldness (MPB), is a common hair loss disorder among middle-aged men. MPB shares similar risk factors with prostate cancer (PrCa), including advancing age, family history, and sex hormones. Several studies have examined the associations between [...] Read more.
Background: Androgenetic alopecia, also known as male pattern baldness (MPB), is a common hair loss disorder among middle-aged men. MPB shares similar risk factors with prostate cancer (PrCa), including advancing age, family history, and sex hormones. Several studies have examined the associations between MPB and PrCa; however, the evidence remains unclear. We carried out an updated meta-analysis of epidemiological studies that examined the relationship between age at onset and patterns of MPB (either frontal, vertex, or both) and their associations with risks of total and aggressive PrCa. Methods: A literature search was performed using PubMed and Web of Science databases for epidemiological studies published between 1 January 2000 and 31 December 2024 that examined the associations between MPB and PrCa. From each eligible study, relevant data were extracted on study design and population, sample size, prevalence of MPB at various ages, and their association with PrCa. Pooled relative risks (RR) and corresponding 95% confidence intervals (CI) were calculated using the Der-Simonian and Laird random-effects models. Heterogeneity across studies was assessed by I2 statistics, while the quality of studies was evaluated using the Newcastle–Ottawa Scale. Results: A total of 19 observational studies, including 17,810 cases and 146,806 controls/non-cases, were analyzed. The prevalence of MPB increased from 5% to 65% with aging and varied across the studies. Both frontal and vertex MPB were associated with a pooled RR of 1.08 (95% CI 1.02–1.14) for total PrCa, but there was no association with frontal-only MPB. Younger-onset MPB (<40 years old) was also associated with an RR = 1.13 (95% CI 0.96–1.31) for PrCa, although results were not statistically significant. Vertex-only MPB was associated with more aggressive PrCa (pooled RR = 1.14; 95% CI 1.02–1.25); however, there was substantial heterogeneity in the definition of aggressive PrCa across the studies. Conclusions: Men with both frontal and vertex MPB have a modestly elevated risk of PrCa. However, most studies were conducted in Caucasian men and they did not evaluate effect modifications by genetic variations in androgen metabolism pathway genes or changes in serum levels of androgens with aging. Large prospective cohort studies with more accurate longitudinal assessment of hair loss patterns are needed to better understand the complex relationship between genetic susceptibility, endogenous hormones, MPB, and subsequent risk of PrCa. Full article
(This article belongs to the Special Issue Urological Cancer: Epidemiology and Genetics)
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16 pages, 7825 KB  
Article
Genome-Wide Characterization and Identification of Auxin Response Factor (ARF) Gene Family Reveals the Regulation of RrARF5 in AsA Metabolism in Rosa roxburghii Tratt. Fruits
by Tu Feng, Zhengliang Sun, Mingchun Liu, Hong Zhao, Yizhong Zhang, Pedro Garcia-Caparros, Bin Yang and Yingdie Yang
Biology 2025, 14(9), 1156; https://doi.org/10.3390/biology14091156 - 1 Sep 2025
Viewed by 855
Abstract
Rosa roxburghii Tratt., a fruit crop known for its high Vitamin C content and other nutritional compounds, has not yet been studied for its auxin response factor (ARF) family members. ARFs are important proteins in auxin-mediated pathways, playing a vital role [...] Read more.
Rosa roxburghii Tratt., a fruit crop known for its high Vitamin C content and other nutritional compounds, has not yet been studied for its auxin response factor (ARF) family members. ARFs are important proteins in auxin-mediated pathways, playing a vital role in plant physiological and biochemical processes such as plant development, and flower and fruit maturation. In the present study, we identified 14 ARF genes (designated as RrARFs) in R. roxburghii, which are distributed across seven chromosomes and grouped into four subfamilies. An analysis of cis-acting elements revealed that these genes might be involved in various biological processes, including plant development, flower development, light responses, cell cycle regulation, phytohormone responses, and responses to abiotic and biotic stresses. A gene expression analysis demonstrated differential expression of RrARF genes across different tissues and stages of fruit development, with four members showing higher expression during the fruit ripening stages. Furthermore, a coexpression analysis identified that RrARF5 was highly coexpressed with RrMDHAR1, a key enzyme involved in Vitamin C biosynthesis. Moreover, transactivation assays and transient overexpression experiments confirmed that RrARF5 activates the transcription of RrMDHAR1. The findings of this study suggest a potential role of the ARF gene family in Vitamin C accumulation in R. roxburghii and enhance our understanding of the diverse regulatory function of the ARF gene family in plants. Full article
(This article belongs to the Section Plant Science)
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12 pages, 3609 KB  
Article
RrYUC10 Positively Regulates Adventitious Root Formation in Rosa rugosa Stem Cuttings
by Mengjuan Bai, Yu Xi, Junqing Xue, Xiangfeng Xu, Mengmeng Xu and Liguo Feng
Horticulturae 2025, 11(9), 1027; https://doi.org/10.3390/horticulturae11091027 - 1 Sep 2025
Viewed by 1434
Abstract
Vegetative propagation through stem cuttings represents the primary mode of reproduction in Rosa species. While numerous studies have reported physiological factors affecting cutting rooting, the genes regulating the formation of adventitious roots in roses have not yet been fully explored and studied. In [...] Read more.
Vegetative propagation through stem cuttings represents the primary mode of reproduction in Rosa species. While numerous studies have reported physiological factors affecting cutting rooting, the genes regulating the formation of adventitious roots in roses have not yet been fully explored and studied. In this study, we demonstrate that Rosa rugosa ‘Feng Hua’ exhibits an indirect rooting pattern, requiring callus formation prior to root primordium differentiation. Phytohormone profiling revealed exceptionally high concentrations of auxin precursors, particularly tryptophan (Trp), in both callus and root tissues. Therefore, we identified and analyzed the members of the YUCCA family, which are the key rate-limiting enzymes in the tryptophan-dependent IAA biosynthesis pathway. A total of 11 RrYUCs family genes were identified, with RT-qPCR analysis showing that RrYUC10 was highly expressed in callus and root tissues. Functional studies confirmed its critical role in adventitious root formation: virus-induced gene silencing (VIGS) of RrYUC10 significantly inhibited AR development, whereas its overexpression enhanced rooting. Our findings have provided a molecular theoretical basis for the rooting of cuttings in roses. Full article
(This article belongs to the Section Propagation and Seeds)
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21 pages, 9699 KB  
Article
Genome-Wide Identification of the ARF Gene Family in Safflower (Carthamus tinctorius L.) and Their Response Patterns to Exogenous Hormone Treatments
by Shuwei Qin, Xinrong Wen, Mengyuan Ma, Jiaxing Wang, Jianhang Zhang, Meihui Huang, Kexin Sun, Ya Zhao, Meng Zhao, Asigul Ismayil, Min Liu and Aiping Cao
Int. J. Mol. Sci. 2025, 26(8), 3773; https://doi.org/10.3390/ijms26083773 - 16 Apr 2025
Cited by 1 | Viewed by 1368
Abstract
Auxin response factors (ARFs) are a class of transcription factors widely present in plants. As an important economic crop, research on the effects of safflower ARFs on endogenous auxin and effective components is relatively limited. In this study, a total of 23 ARF [...] Read more.
Auxin response factors (ARFs) are a class of transcription factors widely present in plants. As an important economic crop, research on the effects of safflower ARFs on endogenous auxin and effective components is relatively limited. In this study, a total of 23 ARF genes were identified from the safflower genome. Sequence alignment and domain analysis indicated the presence of conserved B3 and Auxin_resp domains in these ARFs. Phylogenetic analysis indicated that CtARF could be classified into five subfamilies, a conclusion also supported by gene structure, consensus motifs, and domain compositions. Transcriptome data showed that ARFs are expressed in all flower colors, but the expression levels of ARF family members vary among different flower colors. CtARF19 had relatively higher expression in deep red flowers, CtARF3 had higher expression in white flowers, CtARF2/12 had higher expression in yellow flowers, and CtARF21/22 had higher expression in light red flowers. Protein–protein interaction network analysis indicated that ARF family members (CtARF2/3/4/5/15/18/19/22) are located within the interaction network. Cis-acting element analysis suggested that CtARF genes may be regulated by hormone treatment (AuxRR-core) and abiotic stress, and the results of qRT-PCR also confirmed this. Additionally, the content of endogenous auxin and active components in safflower with different flower colors significantly changed upon treatment with hormones that affect IAA content. In summary, our study provides valuable insights into the biological functions of CtARF genes under exogenous hormone conditions and their effects on active components. Full article
(This article belongs to the Special Issue Research on Plant Genomics and Breeding: 2nd Edition)
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13 pages, 4073 KB  
Article
Resequencing and Transcriptome Analyses Reveal Variations and Expression Patterns of the RR Gene Family in Cucumber
by Ke Su, Wenhong Ao, Zhaolong Sun, Jing Li, Yu Gao, Defang Gan and Jingjing Yang
Genes 2025, 16(4), 409; https://doi.org/10.3390/genes16040409 - 31 Mar 2025
Viewed by 865
Abstract
Background: Cucumber (Cucumis sativus L.) is an important economic crop worldwide. Response regulators (RRs) play crucial roles in plant growth, development, and responses to both biotic and abiotic stresses. Methods: Combined analysis of 182 re-sequencing and transcriptome datasets was conducted to investigate [...] Read more.
Background: Cucumber (Cucumis sativus L.) is an important economic crop worldwide. Response regulators (RRs) play crucial roles in plant growth, development, and responses to both biotic and abiotic stresses. Methods: Combined analysis of 182 re-sequencing and transcriptome datasets was conducted to investigate CsRR variations, with subsequent RT-qPCR experiments confirming its functional significance. Results: In this study, 18 CsRR genes were identified and classified into three groups according to their protein structures: A-ARRs (3), B-ARRs (8), and PRRs (7). Resequencing uncovered critical mutations (non-synonymous SNPs, frameshift, and stop-gain variants) in CsRR genes. Transcriptome data revealed that five genes responded to abiotic stress and four responded to biotic stress. CsPRR1 was upregulated in both resistant and susceptible lines at five dpi, downregulated in resistant plants at nine dpi, and showed no significant difference at 11 dpi. CsPRR2 was consistently upregulated in both lines at 5, 9, and 11 dpi. CsPRR3 was upregulated in resistant lines at nine dpi but downregulated at 11 dpi. CsARR8 was significantly downregulated in both lines at 9 and 11 dpi. Notably, CsPRR2 demonstrated dual functionality related to (i) the regulation of immature fruit skin color via a stop-gain InDel and (ii) resistance to Foc, as the gene was upregulated in both resistant and susceptible lines after inoculation with the pathogen. Conclusions: This study integrated resequencing and transcriptomic data to comprehensively characterize CsRR genes, establishing a foundation for further exploration of their functional mechanisms in cucumber. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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19 pages, 3554 KB  
Article
The Impact Aerobic and Anaerobic Incubations of Poultry Litter Have on Class 1 Integron Resistome and Microbiome
by John J. Maurer, Alexa Hoke, Keshav C. Das, Jian Wu, Mark A. Williams, Sydney Kinstler, Casey Ritz, Gregory P. Pittman, Roy Berghaus and Margie D. Lee
Agriculture 2025, 15(4), 398; https://doi.org/10.3390/agriculture15040398 - 13 Feb 2025
Cited by 1 | Viewed by 1773
Abstract
Animal manure is a desirable fertilizer because of its rich nitrogen, but it also contains a large and diverse reservoir of antimicrobial resistance (AMR) genes (ARGs). To reduce this AMR reservoir, five treatments (passive aeration, forced aeration, static or anaerobic incubations, autoclaving) were [...] Read more.
Animal manure is a desirable fertilizer because of its rich nitrogen, but it also contains a large and diverse reservoir of antimicrobial resistance (AMR) genes (ARGs). To reduce this AMR reservoir, five treatments (passive aeration, forced aeration, static or anaerobic incubations, autoclaving) were assessed for their impact on the poultry litter resistome. Bacterial DNA was extracted from the litter and the qPCR-estimated copy number of 16S rrs, class1 integrons (intI1) and associated resistance genes (aadA, sul1). Then, 16S amplicon metagenomic sequencing was used to determine community diversity and composition. Depending on incubation conditions, class 1 integrons and their associated ARGs were reduced by 0.5 to 1.0 Log10/g poultry litter. Only autoclaving reduced integrons and associated AMR genes by three Log10. Changes in AMR abundance reflected fluctuations in litter bacteriome composition at the family, genus, and sequence variant level. There was a negative correlation between class 1 integron and AMR genes, with genera belonging to Actinobacteria, Firmicutes, and Proteobacteria phyla. While these poultry litter treatments failed to reduce AMR abundance, aerobic and anaerobic treatments reduced taxons that contained pathogenic species. The approach to remediating resistance in poultry litter may be more effective if is focused on reducing bacterial pathogens. Full article
(This article belongs to the Section Farm Animal Production)
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17 pages, 20035 KB  
Article
Comparative Analysis of Ca2+/Cation Antiporter Gene Family in Rosa roxburghii and Enhanced Calcium Stress Tolerance via Heterologous Expression of RrCAX1a in Tobacco
by Tuo Zeng, Liyong Zhu, Wenwen Su, Lei Gu, Hongcheng Wang, Xuye Du, Bin Zhu, Caiyun Wang and Di Wu
Plants 2024, 13(24), 3582; https://doi.org/10.3390/plants13243582 - 22 Dec 2024
Cited by 1 | Viewed by 1340
Abstract
Rosa roxburghii, a calciphilic species native to the mountainous regions of Southwest China, is renowned for its high vitamin C and bioactive components, making it valuable for culinary and medicinal uses. This species exhibits remarkable tolerance to the high-calcium conditions typical of [...] Read more.
Rosa roxburghii, a calciphilic species native to the mountainous regions of Southwest China, is renowned for its high vitamin C and bioactive components, making it valuable for culinary and medicinal uses. This species exhibits remarkable tolerance to the high-calcium conditions typical of karst terrains. However, the underlying mechanisms of this calcium resilience remain unclear. The Ca2+/cation antiporter (CaCA) superfamily plays a vital role in the transport of Ca2+ and other cations and is crucial for plant tolerance to metal stress. However, the roles and evolutionary significance of the CaCA superfamily members in R. roxburghii remain poorly understood. This study identified 22 CaCA superfamily genes in R. roxburghii, categorized into four subfamilies. The gene structures of these RrCaCAs show considerable conservation across related species. Selection pressure analysis revealed that all RrCaCAs are subject to purifying selection. The promoter regions of these genes contain numerous hormone-responsive and stress-related elements. qRT-PCR analyses demonstrated that H+/cation exchanger (CAX) RrCAX1a and RrCAX3a were highly responsive to Ca2+ stress, cation/Ca2+ exchanger (CCX) RrCCX4 to Mg2+ stress, and RrCCX11a to Na+ stress. Subcellular localization indicated that RrCAX1a is localized to the plant cell membrane, and its stable transformation in tobacco confirmed its ability to confer enhanced resistance to heavy Ca2+ stresses, highlighting its crucial role in the high-calcium tolerance mechanisms of R. roxburghii. This research establishes a foundation for further molecular-level functional analyses of the adaptation mechanisms of R. roxburghii to high-calcium environments. Full article
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12 pages, 5357 KB  
Article
C2H2 Zinc Finger Protein Family Analysis of Rosa rugosa Identified a Salt-Tolerance Regulator, RrC2H2-8
by Yong Xu, Yuqing Shi, Weijie Zhang, Kaikai Zhu, Liguo Feng and Jianwen Wang
Plants 2024, 13(24), 3580; https://doi.org/10.3390/plants13243580 - 22 Dec 2024
Cited by 6 | Viewed by 1315
Abstract
Rosa rugosa is a representative aromatic species. Wild roses are known for their strong tolerance to highly salty environments, whereas cultivated varieties of roses exhibit lower salt stress tolerance, limiting their development and industrial expansion. Previous studies have shown that C2H2-type zinc finger [...] Read more.
Rosa rugosa is a representative aromatic species. Wild roses are known for their strong tolerance to highly salty environments, whereas cultivated varieties of roses exhibit lower salt stress tolerance, limiting their development and industrial expansion. Previous studies have shown that C2H2-type zinc finger proteins play a crucial role in plants’ resistance to abiotic stresses. In this study, 102 C2H2-type zinc finger genes (RrC2H2s) were identified in R. rugosa via a comprehensive approach. These genes were categorized into three lineages, and their motif constitutions were grouped into four classes. RrC2H2s were distributed across all seven rose chromosomes, with 15 paralogous gene pairs identified within synteny regions. Additionally, 43 RrC2H2s showed differential expression across various tissues under salt stress, with RrC2H2-8 being the only gene consistently repressed in all tissues. Subcellular localization analysis revealed that the RrC2H2-8 protein was localized in the nucleus. The heterologous expression of RrC2H2-8 in Arabidopsis significantly improved its growth under salt stress compared to the wild-type (WT) plants. Furthermore, the malondialdehyde content in the roots of transgenic Arabidopsis was significantly lower than that in the WT, suggesting that RrC2H2-8 enhanced salt tolerance by reducing cellular damage. This study provides a systematic understanding of the RrC2H2 family and identifies RrC2H2-8 as a regulator of salt tolerance, laying a foundation for future research on the mechanisms of salt stress regulation by RrC2H2. Full article
(This article belongs to the Section Plant Molecular Biology)
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20 pages, 11429 KB  
Article
Genome-Wide Analysis of C2H2 Zinc Finger Gene Family and Exploration of Genes Related to Prickle Development in Zanthoxylum armatum
by Nuo Wang, Renhua Huang, Hualin Zou, Yuwei Yi, Jiabao Ye, Weiwei Zhang, Feng Xu and Yongling Liao
Horticulturae 2024, 10(12), 1371; https://doi.org/10.3390/horticulturae10121371 - 20 Dec 2024
Viewed by 1624
Abstract
Zanthoxylum armatum (Z. armatum) is a significant economic tree species known for its medicinal and edible properties. However, the presence of prickles on Z. armatum poses a considerable challenge to the advancement of its industry. Numerous studies have indicated that the [...] Read more.
Zanthoxylum armatum (Z. armatum) is a significant economic tree species known for its medicinal and edible properties. However, the presence of prickles on Z. armatum poses a considerable challenge to the advancement of its industry. Numerous studies have indicated that the C2H2 zinc finger protein (C2H2-ZFPs) families are crucial in the development of plant trichomes or prickles. This study identified 78 ZaC2H2 genes from the Z. armatum genome, categorizing them into three groups and analyzing their protein physicochemical properties, chromosomal locations, conserved domains, and gene structures. The evolutionary analysis indicates that the amplification of ZaC2H2 genes primarily results from whole-genome duplication or segmental duplication, and these genes have undergone strong purifying selection pressure throughout their evolutionary history. The analysis of cis-acting elements revealed that they contain various hormone response elements, such as ABRE, AuxRR, the CGTCA motif, GARE motifs, and TCA elements, which are responsive to ABA, IAA, MeJA, GA, and SA signals. RT-qPCR was employed to assess the expression levels of the candidate genes ZaC2H2-45, ZaC2H2-46, ZaC2H2-49, and ZaC2H2-55 under the treatment of five hormones. The results indicated that the expression levels of the ZaC2H2-46 and ZaC2H2-55 genes were significantly up-regulated under NAA, SA, and MeJA treatments. These results will help to further understand the characteristics of the ZaC2H2 gene family and provide a theoretical basis for studying the development of prickles. Full article
(This article belongs to the Section Genetics, Genomics, Breeding, and Biotechnology (G2B2))
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14 pages, 10118 KB  
Article
RrWRKY1, a Transcription Factor, Is Involved in the Regulation of the Salt Stress Response in Rosa rugosa
by Fengqi Zang, Qichao Wu, Zhe Li, Ling Li, Xiaoman Xie, Boqiang Tong, Shuhan Yu, Zhaoan Liang, Chunxue Chu, Dekui Zang and Yan Ma
Plants 2024, 13(21), 2973; https://doi.org/10.3390/plants13212973 - 24 Oct 2024
Cited by 3 | Viewed by 1642
Abstract
Salt stress has become a major environmental problem affecting plant growth and development. Some WRKY transcription factors have been reported to be involved in the salt stress response in plants. However, there are few studies on the involvement of WRKYs in the salt [...] Read more.
Salt stress has become a major environmental problem affecting plant growth and development. Some WRKY transcription factors have been reported to be involved in the salt stress response in plants. However, there are few studies on the involvement of WRKYs in the salt stress response in Rosa rugosa. In this study, we isolated a salt tolerance gene, RrWRKY1, from R. rugosa. RrWRKY1 was found to belong to Group I of the WRKY family, and it was specifically expressed in leaves and petals. RrWRKY1 expression was upregulated under NaCl stress in rose leaves. After silencing RrWRKY1 in R. rugosa, transgenic plants showed dry leaves and black and brown veins, indicating sensitivity to salt stress. At the same time, the transcription levels of the salt tolerance-related genes RrNHX1, RrABF2, RrRD22, RrNCED1, and RrHKT1 also changed significantly. The superoxide dismutase (SOD) and peroxidase (POD) activities decreased, the proline content decreased, and the malondialdehyde (MDA) content in the gene-silenced plants increased, indicating that RrWRKY1 regulates the salt tolerance of R. rugosa. In addition, the overexpression of RrWRKY1 in Arabidopsis thaliana improved the germination rate and the average of the main root and lateral root lengths, and the transgenic plants had a larger number of lateral roots than the WT plants under salt stress. This study provides candidate gene resources for salinity tolerance breeding and a theoretical basis for analyzing the salinity tolerance mechanism of the WRKY gene. Full article
(This article belongs to the Special Issue Abiotic Stress Responses in Plants)
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16 pages, 4102 KB  
Article
The TIR1/AFB Family in Solanum melongena: Genome-Wide Identification and Expression Profiling under Stresses and Picloram Treatment
by Wenchao Du, Umer Karamat, Liuqing Cao, Yunpeng Li, Haili Li, Haoxin Li, Lai Wei, Dongchen Yang, Meng Xia, Qiang Li and Xueping Chen
Agronomy 2024, 14(7), 1413; https://doi.org/10.3390/agronomy14071413 - 28 Jun 2024
Cited by 1 | Viewed by 1791
Abstract
TIR1/AFB proteins are a class of auxin receptors with key roles in plant development and biotic and abiotic stress responses; several have been identified as targets of the auxin-mimicking herbicide picloram. In this study, we identified five putative TIR1/AFB gene family members in [...] Read more.
TIR1/AFB proteins are a class of auxin receptors with key roles in plant development and biotic and abiotic stress responses; several have been identified as targets of the auxin-mimicking herbicide picloram. In this study, we identified five putative TIR1/AFB gene family members in the important vegetable crop Solanum melongena (eggplant) and characterized them using bioinformatics tools and gene expression analyses. Phylogenetic analysis of the TIR1/AFBs classified them into three subgroups based on their Arabidopsis and Solanum lycopersicum homologs. AFB6 homologs were present only in S. melongena and S. lycopersicum, whereas AFB2/3 homologs were found only in Arabidopsis. One pair of S. melongena TIR1 homologs were located in syntenic regions in the genome and appeared to have arisen by segmental duplication. Promoter analysis revealed 898 cis-elements in the TIR1/AFB promoters, 125 of which were related to hormones, stress, light, or growth responses, but only SmAFB5 had a cis-acting regulatory element involved in auxin responsiveness (AuxRR-core). RNA sequencing and expression profiling showed that the TIR1/AFB genes were differentially expressed at different growth stages and in response to light, temperature, and drought. Only SmTIR1A expression was significantly induced by picloram treatment and different growth stages. TIR1/AFB expression is regulated by microRNAs (miRNAs) in other plant species, and we identified 6 or 29 miRNAs that potentially targeted the five TIR1/AFB genes on the basis of comparisons with S. lycopersicum and S. tuberosum miRNAs, respectively. Three-dimensional protein structure predictions revealed that all the TIR1/AFB proteins were very similar in structure, differing only in the numbers of alpha helices and in one angle linking an α helix and a β sheet. For measuring the function of TIR1/AFB genes in response to drought, SmAFB5 was selected, and knockdown by virus-induced gene silence (VIGS) 35S::SmAFB5 lines showed resistance to drought compared to controls. These analyses provide insight into the potential functions of TIR1/AFBs during growth and in response to stress; they highlight differences among the SmTIR1/AFBs that may be useful for eggplant breeding. Full article
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17 pages, 3420 KB  
Review
Mezigdomide—A Novel Cereblon E3 Ligase Modulator under Investigation in Relapsed/Refractory Multiple Myeloma
by Monique A. Hartley-Brown, Clifton C. Mo, Omar Nadeem, Shonali Midha, Jacob P. Laubach and Paul G. Richardson
Cancers 2024, 16(6), 1166; https://doi.org/10.3390/cancers16061166 - 15 Mar 2024
Cited by 12 | Viewed by 7363
Abstract
Mezigomide is an oral cereblon E3 ligase modulator (CELMoD) that is under clinical investigation in patients with relapsed/refractory (RR) multiple myeloma (MM). Like other CELMoD compounds, mezigdomide acts by altering the conformation of cereblon within the cullin 4A ring ligase–cereblon (CRL4CRBN) E3 ubiquitin [...] Read more.
Mezigomide is an oral cereblon E3 ligase modulator (CELMoD) that is under clinical investigation in patients with relapsed/refractory (RR) multiple myeloma (MM). Like other CELMoD compounds, mezigdomide acts by altering the conformation of cereblon within the cullin 4A ring ligase–cereblon (CRL4CRBN) E3 ubiquitin ligase complex, thereby recruiting novel protein substrates for selective proteasomal degradation. These include two critical lymphoid transcription factors, Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3), also known as Ikaros and Aiolos, which have important roles in the development and differentiation of hematopoietic cells, in MM pathobiology, and in suppressing the expression of interferon-stimulating genes and T-cell stimulation. Among the CELMoDs, mezigdomide has the greatest cereblon-binding potency, plus the greatest potency for the degradation of Ikaros and Aiolos and subsequent downstream antimyeloma effects. Preclinical studies of mezigdomide have demonstrated its anti-proliferative and apoptotic effects in MM, along with its immune-stimulatory effects and its synergistic activity with other antimyeloma agents, including in lenalidomide-/pomalidomide-resistant MM cell lines and mouse xenograft models. Early-phase clinical trial data indicate notable activity in heavily pretreated patients with RRMM, including those with triple-class-refractory disease, together with a tolerable and manageable safety profile. This review summarizes current preclinical and clinical findings with mezigdomide and its potential future roles in the treatment of MM. Full article
(This article belongs to the Section Cancer Therapy)
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15 pages, 4822 KB  
Article
Genome-Wide Identification and Expression Profiling of the Response Regulator (RR) Gene Family in Pecan Reveals Its Possible Association with Callus Formation during Grafting
by Yan Zhang, Zhanhui Jia, Guoming Wang, Mengxin Hou, Min Zhai, Longjiao Hu, Jiping Xuan and Zhenghai Mo
Forests 2024, 15(3), 473; https://doi.org/10.3390/f15030473 - 3 Mar 2024
Cited by 1 | Viewed by 1871
Abstract
Response regulator (RR) is the core component of cytokinin (CK) signaling, and it regulates the expression of numerous downstream CK-responsive genes. However, the knowledge regarding the pecan RR (CiRR) gene family is still limited. In this study, we first monitored trans-zeatin [...] Read more.
Response regulator (RR) is the core component of cytokinin (CK) signaling, and it regulates the expression of numerous downstream CK-responsive genes. However, the knowledge regarding the pecan RR (CiRR) gene family is still limited. In this study, we first monitored trans-zeatin riboside (tZR) content in the graft union 0, 7, 14, and 32 days after grafting and then conducted genome-wide analysis and expression profiling of the CiRR gene family using an available genome sequence and RNA-seq dataset, aiming to better understand the roles of CK during pecan grafting. The dynamic contents of tZR showed an increased trend during the specific period for both the scion and rootstock. There were 20 CiRRs in the pecan genome, including 12 type A CiRRs, 5 type B members, and 3 type C genes. All members contained a receiver domain and type B CiRRs possessed an additional Myb-like DNA-binding domain. Promoter analysis showed that the CiRR gene family contained cis-elements associated with growth and development, hormones, and stress. A total of 10 genes, including CiRR18/9/4a/14a/12c/5/12b/14b/2b/2a, were abundantly expressed in the samples of different tissues, drought stress, and kernel development. There were 12 genes (CiRR5/18/4a/12b/2b/12c/14b/2a/14a/4b/9/11a) showing active expressions during grafting, and weighted gene co-expression network analysis (WGCNA) grouped them into six modules. Among them, CiRR14a and CiRR12b were the hub genes for the turquoise and brown modules, respectively. Functional annotation indicated that the turquoise module was associated with gene transcription and translation, while the brown module was related to cell proliferation. Our results suggest that the CiRR gene family central to CK signaling is probably involved in callus formation during pecan grafting. Full article
(This article belongs to the Special Issue Advances in Tree Germplasm Innovation and High-Efficiency Propagation)
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16 pages, 13303 KB  
Article
Genome-Wide Identification of the RR Gene Family and Its Expression Analysis in Response to TDZ Induction in Rhododendron delavayi
by Lvchun Peng, Xuejiao Li, Yan Gao, Weijia Xie, Lu Zhang, Jie Song, Shifeng Li and Zhengxiong Zhao
Plants 2023, 12(18), 3250; https://doi.org/10.3390/plants12183250 - 13 Sep 2023
Cited by 6 | Viewed by 2057
Abstract
The cytokinin response regulator (RR) gene is essential for cytokinin signal transduction, which plays a crucial role in plant growth and development. Here, we applied bioinformatics to Rhododendron delavayi’s genome to identify its RR gene family and systematically analyzed their gene characteristics, [...] Read more.
The cytokinin response regulator (RR) gene is essential for cytokinin signal transduction, which plays a crucial role in plant growth and development. Here, we applied bioinformatics to Rhododendron delavayi’s genome to identify its RR gene family and systematically analyzed their gene characteristics, phylogenetic evolution, chromosomal localization, collinearity analysis, promoter cis-elements, and expression patterns. Overall, 33 RdRR genes were distinguished and classified into three types. All these genes harbored motif 5 (YEVTTVNSGLEALELLRENKB), the most conserved one, along with the plant-conserved domain (REC domain), and could be mapped to 10 chromosomes with four gene pairs of segmental replication events but no tandem replication events; 13 RdRR genes showed collinearity with Arabidopsis thaliana genes. Promoter analysis revealed multiple hormone-related cis-elements in the RR genes. After a TDZ (thidiazuron) treatment, 13 genes had higher expression levels than the control, whose magnitude of change depended on the developmental stage of leaves’ adventitious buds. The expression levels of RdRR14, RdRR17, RdRR20, and RdRR24 agreed with the average number of adventitious buds post-TDZ treatment. We speculate that these four genes could figure prominently in bud regeneration from R. delavayi leaves in vitro. This study provides detailed knowledge of RdRRs for research on cytokinin signaling and RdRR functioning in R. delavayi. Full article
(This article belongs to the Special Issue Flower Germplasm Resource and Genetic Breeding)
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Article
GA20ox Family Genes Mediate Gibberellin and Auxin Crosstalk in Moso bamboo (Phyllostachys edulis)
by Yucong Bai, Yali Xie, Miaomiao Cai, Jutang Jiang, Chongyang Wu, Huifang Zheng and Jian Gao
Plants 2023, 12(15), 2842; https://doi.org/10.3390/plants12152842 - 1 Aug 2023
Cited by 7 | Viewed by 3374
Abstract
Moso bamboo (Phyllostachys edulis) is one of the fastest growing plants. Gibberellin (GA) is a key phytohormone regulating growth, but there are few studies on the growth of Moso bamboo regulated by GA. The gibberellin 20 oxidase (GA20ox) gene [...] Read more.
Moso bamboo (Phyllostachys edulis) is one of the fastest growing plants. Gibberellin (GA) is a key phytohormone regulating growth, but there are few studies on the growth of Moso bamboo regulated by GA. The gibberellin 20 oxidase (GA20ox) gene family was targeted in this study. Chromosomal distribution and collinearity analysis identified 10 GA20ox genes evenly distributed on chromosomes, and the family genes were relatively conservative in evolution. The genetic relationship of GA20ox genes had been confirmed to be closest in different genera of plants in a phylogenetic and selective pressure analysis between Moso bamboo and rice. About 1/3 GA20ox genes experienced positive selective pressure with segmental duplication being the main driver of gene family expansion. Analysis of expression patterns revealed that only six PheGA20ox genes were expressed in different organs of shoot development and flowers, that there was redundancy in gene function. Underground organs were not the main site of GA synthesis in Moso bamboo, and floral organs are involved in the GA biosynthesis process. The auxin signaling factor PheARF47 was located upstream of PheGA20ox3 and PheGA20ox6 genes, where PheARF47 regulated PheGA20ox3 through cis-P box elements and cis-AuxRR elements, based on the result that promoter analysis combined with yeast one-hybrid and dual luciferase detection analysis identified. Overall, we identified the evolutionary pattern of PheGA20ox genes in Moso bamboo and the possible major synthesis sites of GA, screened for key genes in the crosstalk between auxin and GA, and laid the foundation for further exploration of the synergistic regulation of growth by GA and auxin in Moso bamboo. Full article
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