Microtubule-associated protein SlMAP70 interacts with IQ67-domain protein SlIQD21a to regulate fruit shape in tomato.

Tomato (Solanum lycopersicum) fruit shape is related to microtubule organization and the activity of microtubule-associated proteins (MAPs). However, insights into the mechanism of fruit shape formation from a cell biology perspective remain limited. Analysis of the tissue expression profiles of different microtubule regulators revealed that functionally distinct classes of MAPs, including members of the plant-specific MICROTUBULE-ASSOCIATED PROTEIN 70 (MAP70) and IQ67 DOMAIN (IQD, also named SUN in tomato) families, are differentially expressed during fruit development. SlMAP70-1-3 and SlIQD21a are highly expressed during fruit initiation, which relates to the dramatic microtubule pattern rearrangements throughout this developmental stage of tomato fruits. Transgenic tomato lines overexpressing SlMAP70-1 or SlIQD21a produced elongated fruits with reduced cell circularity and microtubule anisotropy, while their loss-of-function mutants showed the opposite phenotype, harboring flatter fruits. Fruits were further elongated in plants coexpressing both SlMAP70-1 and SlIQD21a. We demonstrated that SlMAP70s and SlIQD21a physically interact and that the elongated fruit phenotype is likely due to microtubule stabilization induced by the SlMAP70-SlIQD21a interaction. Together, our results identify SlMAP70 proteins and SlIQD21a as important regulators of fruit elongation and demonstrate that manipulating microtubule function during early fruit development provides an effective approach to alter fruit shape.

Molecular classification reveals the sensitivity of lung adenocarcinoma to radiotherapy and immunotherapy: multi-omics clustering based on similarity network fusion.

BACKGROUND: Due to individual differences in tumors and immune systems, the response rate to immunotherapy is low in lung adenocarcinoma (LUAD) patients. Combinations with other therapeutic strategies improve the efficacy of immunotherapy in LUAD patients. Although radioimmunotherapy has been demonstrated to effectively suppress tumors, the underlying mechanisms still need to be investigated. METHODS: Total RNA from LUAD cells was sequenced before and after radiotherapy to identify differentially expressed radiation-associated genes. The similarity network fusion (SNF) algorithm was applied for molecular classification based on radiation-related genes, immune-related genes, methylation data, and somatic mutation data. The changes in gene expression, prognosis, immune cell infiltration, radiosensitivity, chemosensitivity, and sensitivity to immunotherapy were assessed for each subtype. RESULTS: We used the SNF algorithm and multi-omics data to divide TCGA-LUAD patients into three subtypes. Patients with the CS3 subtype had the best prognosis, while those with the CS1 and CS2 subtypes had poorer prognoses. Among the strains tested, CS2 exhibited the most elevated immune cell infiltration and expression of immune checkpoint genes, while CS1 exhibited the least. Patients in the CS2 subgroup were more likely to respond to PD-1 immunotherapy. The CS2 patients were most sensitive to docetaxel and cisplatin, while the CS1 patients were most sensitive to paclitaxel. Experimental validation of signature genes in the CS2 subtype showed that inhibiting the expression of RHCG and TRPA1 could enhance the sensitivity of lung cancer cells to radiation. CONCLUSIONS: In summary, this study identified a risk classifier based on multi-omics data that can guide treatment selection for LUAD patients.

Exploring the influence of a single-nucleotide mutation in EIN4 on tomato fruit firmness diversity through fruit pericarp microstructure.

Tomato (Solanum lycopersicum) stands as one of the most valuable vegetable crops globally, and fruit firmness significantly impacts storage and transportation. To identify genes governing tomato firmness, we scrutinized the firmness of 266 accessions from core collections. Our study pinpointed an ethylene receptor gene, SlEIN4, located on chromosome 4 through a genome-wide association study (GWAS) of fruit firmness in the 266 tomato core accessions. A single-nucleotide polymorphism (SNP) (A → G) of SlEIN4 distinguished lower (AA) and higher (GG) fruit firmness genotypes. Through experiments, we observed that overexpression of SlEIN4AA significantly delayed tomato fruit ripening and dramatically reduced fruit firmness at the red ripe stage compared with the control. Conversely, gene editing of SlEIN4AA with CRISPR/Cas9 notably accelerated fruit ripening and significantly increased fruit firmness at the red ripe stage compared with the control. Further investigations revealed that fruit firmness is associated with alterations in the microstructure of the fruit pericarp. Additionally, SlEIN4AA positively regulates pectinase activity. The transient transformation assay verified that the SNP (A → G) on SlEIN4 caused different genetic effects, as overexpression of SlEIN4GG increased fruit firmness. Moreover, SlEIN4 exerts a negative regulatory role in tomato ripening by impacting ethylene evolution through the abundant expression of ethylene pathway regulatory genes. This study presents the first evidence of the role of ethylene receptor genes in regulating fruit firmness. These significant findings will facilitate the effective utilization of firmness and ripening traits in tomato improvement, offering promising opportunities for enhancing tomato storage and transportation capabilities.

EARLY FLOWERING is a dominant gain-of-function allele of FANTASTIC FOUR 1/2c that promotes early flowering in tomato.

Flowering time, an important factor in plant adaptability and genetic improvement, is regulated by various genes in tomato (Solanum lycopersicum). In this study, we characterized a tomato mutant, EARLY FLOWERING (EF), that developed flowers much earlier than its parental control. EF is a dominant gain-of-function allele with a T-DNA inserted 139 bp downstream of the stop codon of FANTASTIC FOUR 1/2c (FAF1/2c). The transcript of SlFAF1/2c was at elevated levels in the EF mutant. Overexpressing SlFAF1/2c in tomato plants phenocopied the early flowering trait of the EF mutant. Knocking out SlFAF1/2c in the EF mutant reverted the early flowering phenotype of the mutant to the normal flowering time of the wild-type tomato plants. SlFAF1/2c promoted the floral transition by shortening the vegetative phase rather than by reducing the number of leaves produced before the emergence of the first inflorescence. The COP9 signalosome subunit 5B (CSN5B) was shown to interact with FAF1/2c, and knocking out CSN5B led to an early flowering phenotype in tomato. Interestingly, FAF1/2c was found to reduce the accumulation of the CSN5B protein by reducing its protein stability. These findings imply that FAF1/2c regulates flowering time in tomato by reducing the accumulation and stability of CSN5B, which influences the expression of SINGLE FLOWER TRUSS (SFT), JOINTLESS (J) and UNIFLORA (UF). Thus, a new allele of SlFAF1/2c was discovered and found to regulate flowering time in tomato.

Defective mutations in STAY-GREEN 1, PHYTOENE SYNTHASE 1, and MYB12 genes lead to formation of green ripe fruit in tomato.

Modern tomatoes produce colorful mature fruits, but many wild tomato ancestors form green or gray green ripe fruits. Here, tomato cultivar 'Lvbaoshi' (LBS) that produces green ripe fruits was found to contain three recessive loci responsible for fruit development. The colorless peel of LBS fruits was caused by a 603 bp deletion in the promoter of SlMYB12. The candidate genes of the remaining two loci were identified as STAY-GREEN 1 (SlSGR1) and PHYTOENE SYNTHASE 1 (SlPSY1). SGR1 and PSY1 co-suppression by RNAi converted the pink fruits into green ripe fruits in transgenic plants. An amino acid change in PSY1 and a deletion in the promoter of SGR1 were also identified in several wild tomatoes bearing green or gray ripe fruits. Overexpression of PSY1 from green ripe fruit wild tomatoes in LBS plants could only partially rescue the green ripe fruit phenotype of LBS, and transgenic lines expressing ProSGR1::SGR1 from Solanum pennellii also failed to convert purple-flesh into red-flesh fruits. This work uncovers a novel regulatory mechanism by which SlMYB12, SlPSY1, and SlSGR1 control fruit color in cultivated and some wild tomato species.

A mutation in a C2H2-type zinc finger transcription factor contributed to the transition toward self-pollination in cultivated tomato.

The degree of stigma exsertion has a major influence on self-pollination efficiency in tomato, and its improvement is essential for raising productivity and for fixing advantageous traits in cultivated tomato. To study the evolution of stigma exsertion degree in tomato, we searched for genes associated with this trait and other aspects of flower morphology, including the lengths of anthers, styles, and ovaries. We performed a genome-wide association on 277 tomato accessions and discovered a novel stigma exsertion gene (SE3.1). We reannotated the structure of the gene, which encodes a C2H2-type zinc finger transcription factor. A mutation of the lead single nucleotide polymorphism creates a premature termination codon in SE3.1 and an inserted stigma in cultivated tomatoes. SE3.1 is essential for the conversion of flush stigmas to inserted stigmas. This conversion has a major impact on the rate of self-fertilization. Intriguingly, we found that both SE3.1 and Style2.1 contribute to the transition from stigma exsertion to insertion during the domestication and improvement of tomato. Style2.1 controls the first step of exserted stigmas to flush stigmas, and SE3.1 controls the second step of flush stigmas to inserted stigmas. We provide molecular details for the two-step process that controls the transition from stigma exsertion to insertion, which is of great agronomic importance in tomato.

SERCA2 protects against cisplatin-induced damage of auditory cells: Possible relation with alleviation of ER stress.

AIMS: SERCA2, one of the P-type pumps encoded by gene ATP2A2, is the only calcium reflux channel of the endoplasmic reticulum (ER) and participates in maintaining calcium homeostasis. The present study was designed to explore SERCA2 expression pattern in auditory hair cells and the possible mechanism underlying the effects of SERCA2 on cisplatin-induced ototoxicity. MAIN METHODS: The SERCA2 expression pattern in cochlea hair cells and HEI-OC1 cells was measured by Western blot (WB) and immunofluorescence staining. The apoptosis and its related factors were detected by TUNEL assay and WB. The expression levels of ER stress-related factors, ATF6, PERK, IRE1α, and GRP78, were measured via WB. As for the determination of SERCA2 overexpression and knockdown, plasmids and lentiviral vectors were constructed, respectively. KEY FINDINGS: We found that SERCA2 was highly expressed in cochlea hair cells and HEI-OC1 cells. Of note, the level of SERCA2 expression in neonatal mice was remarkably higher than that in adult mice. Under the exposure of 30 µM cisplatin, SERCA2 was down-regulated significantly compared with the control group. In addition, cisplatin administration triggered the occurrence of ER stress and apoptosis. Those events were reversed by overexpressing SERCA2. On the contrary, SERCA2 knockdown could aggravate the above processes. SIGNIFICANCE: The findings from the present study disclose, for the first time, that SERCA2 is abundantly expressed in cochlea hair cells, and the suppression of SERCA2 caused by cisplatin could trigger ER homeostasis disruption, thereby implying that SERCA2 might be a promising target to prevent cisplatin-induced cytotoxicity of hair cells.

CRISPR/Cas13a-triggered entropy-driven amplification for colorimetric and fluorescent dual-mode detection of microRNA.

MicroRNAs (miRNAs) are crucial biomarkers for the early detection and monitoring of disease progression of chronic obstructive pulmonary disease (COPD). Herein, we have devised a method for detecting miRNA using a combination of colorimetric and graphene oxide-based fluorescent techniques. The target miRNA in our design could precisely activate the trans-cleavage activity of the CRISPR-Cas13a system. The activated Cas13a enzyme cuts the "rUrU" section in the P1 probe, generating a nicking site to induce entropy-driven amplification (EDA). One of the available EDA products has the capability to unfold the hairpin probe, thereby initiating the catalytic hairpin assembly, exposing the G-quadruplex structure, facilitating the subsequent color response. The fuel strand labeled with Cy3 successfully established a double-stranded DNA structure with DNA3, and consequently the Cy3 would not be quenched by graphene oxide (GO). The implementation of the dual-mode technique in this method yields greater benefits in terms of improving the precision and consistency of the miRNA measurements. The developed method has the capability to fluorescently measure miRNA-21 levels down to a concentration of 5.8 fM. In addition, the analysis of miRNA targets from clinical samples using this method demonstrates its promising utility in the fields of biomedical research of COPD.

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OBJECTIVES: To explore the risk factors associated with cow's milk protein allergy (CMPA) in infants. METHODS: This study was a multicenter prospective nested case-control study conducted in seven medical centers in Beijing, China. Infants aged 0-12 months were included, with 200 cases of CMPA infants and 799 control infants without CMPA. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for the occurrence of CMPA. RESULTS: Univariate logistic regression analysis showed that preterm birth, low birth weight, birth from the first pregnancy, firstborn, spring birth, summer birth, mixed/artificial feeding, and parental history of allergic diseases were associated with an increased risk of CMPA in infants (P<0.05). Multivariate logistic regression analysis revealed that firstborn (OR=1.89, 95%CI: 1.14-3.13), spring birth (OR=3.42, 95%CI: 1.70-6.58), summer birth (OR=2.29, 95%CI: 1.22-4.27), mixed/artificial feeding (OR=1.57, 95%CI: 1.10-2.26), parental history of allergies (OR=2.13, 95%CI: 1.51-3.02), and both parents having allergies (OR=3.15, 95%CI: 1.78-5.56) were risk factors for CMPA in infants (P<0.05). CONCLUSIONS: Firstborn, spring birth, summer birth, mixed/artificial feeding, and a family history of allergies are associated with an increased risk of CMPA in infants.

SlBBX20 attenuates JA signalling and regulates resistance to Botrytis cinerea by inhibiting SlMED25 in tomato.

Jasmonic acid (JA) plays an important role in regulating plant growth and defence responses. Here, we show that a transcription factor that belongs to the B-box (BBX) family named SlBBX20 regulates resistance to Botrytis cinerea in tomato by modulating JA signalling. The response to JA was significantly suppressed when SlBBX20 was overexpressed in tomato. By contrast, the JA response was enhanced in SlBBX20 knockout lines. RNA sequencing analysis provided more evidence that SlBBX20 modulates the expression of genes that are involved in JA signalling. We found that SlBBX20 interacts with SlMED25, a subunit of the Mediator transcriptional co-activator complex, and prevents the accumulation of the SlMED25 protein and transcription of JA-responsive genes. JA contributes to the defence response against necrotrophic pathogens. Knocking out SlBBX20 or overexpressing SlMED25 enhanced tomato resistance to B. cinerea. The resistance was impaired when SlBBX20 was overexpressed in plants that also overexpressed SlMED25. These data show that SlBBX20 attenuates JA signalling by regulating SlMED25. Interestingly, in addition to developing enhanced resistance to B. cinerea, SlBBX20-KO plants also produced higher fruit yields. SlBBX20 is a potential target gene for efforts that aim to develop elite crop varieties using gene editing technologies.

SlTCP24 and SlTCP29 synergistically regulate compound leaf development through interacting with SlAS2 and activating transcription of SlCKX2 in tomato.

The complexity of compound leaves results primarily from the leaflet initiation and arrangement during leaf development. However, the molecular mechanism underlying compound leaf development remains a central research question. SlTCP24 and SlTCP29, two plant-specific transcription factors with the conserved TCP motif, are shown here to synergistically regulate compound leaf development in tomato. When both of them were knocked out simultaneously, the number of leaflets significantly increased, and the shape of the leaves became more complex. SlTCP24 and SlTCP29 could form both homodimers and heterodimers, and such dimerization was impeded by the leaf polarity regulator SlAS2, which interacted with SlTCP24 and SlTCP29. SlTCP24 and SlTCP29 could bind to the TCP-binding cis-element of the SlCKX2 promoter and activate its transcription. Transgenic plants with SlTCP24 and SlTCP29 double-gene knockout had a lowered transcript level of SlCKX2 and an elevated level of cytokinin. This work led to the identification of two key regulators of tomato compound leaf development and their targeted genes involved in cytokinin metabolic pathway. A model of regulation of compound leaf development was proposed based on observations of this study.

Gender differences in alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period (October 20, 2020-April 5, 2021) in China.

BACKGROUND: This study aimed to assess the prevalence and the gender-specific risk factors of alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period in China. METHOD: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was used to identify respondents with alcohol abuse/dependence. A questionnaire on basic demographics and mental distresses (learning burnout, depression symptoms, anxiety symptoms, excessive daytime sleepiness, and history of mental disorders) was used. The logistic regression model was used to explore the associations between the above characteristics and alcohol abuse/dependence. RESULTS: A total of 3,412 medical undergraduates were included in the analysis. Males showed a higher prevalence of alcohol abuse/dependence than females (16.6% vs 7.4%, p < 0.001). Alcohol abuse/dependence was associated with learning burnout (OR: 2.168, p < 0.001) and having a partner (OR: 1.788 p = 0.001) among female medical undergraduates. Among male medical undergraduates, excessive daytime sleepiness (OR: 1.788 p = 0.001) and older age (OR: 1.788, p = 0.001) were independently associated with alcohol abuse/dependence. CONCLUSION: Alcohol abuse/dependence was common among medical undergraduates during the post-COVID­19 pandemic period. Substantial gender differences in the prevalence and risk factors of alcohol abuse/dependence were found among medical undergraduates in this study, which highlighted the need for timely gender-specific screening and interventions. However, the cross-sectional design adopted in this study has limited the examination of causality, thus further longitudinal studies are warranted.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) protects hair cells from cisplatin-induced ototoxicity in vitro: possible relation to the activities of p38 MAPK signaling pathway.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) gene encodes rate-limiting enzyme in cholesterol biosynthesis, which is related to cell proliferation and mitochondrial function. The present study was designed to explore the expression of HMGCR in murine cochlear hair cells and HEI-OC1 cells and the possible mechanisms underpinning the actions of HMGCR in cisplatin-induced ototoxicity, with special attention given to p38 mitogen-activated protein kinase (MAPK) activities in vitro. The expressions of HMGCR, p-p38, cleaved caspase-3 and LC3B was measured by immunofluorescence and western blot. JC-1 staining and MitoSOX Red were used to detect mitochondria membrane potential (MMP) and reactive oxygen species (ROS) levels respectively. The apoptosis of auditory cells was assessed by TUNEL staining and flow cytometry. Protein levels of bcl2/bax and beclin1 were examined by western blot. We found that HMGCR was widely expressed in the auditory cells, of both neonatal mice and 2-month-old mice, in cytoplasm, nucleus and stereocilia. Moreover, 30 µM cisplatin elicited the formation of ROS, which, in turn, led to HMGCR reduction, activating p38 kinase-related apoptosis and autophagy in auditory cells. Meanwhile, co-treatment with ROS scavenger at a concentration of 2 mM, N-acetyl-L-cysteine (NAC), could alleviate the aforementioned changes. In addition, HMGCR silencing resulted in higher p38 MAPK-mediated apoptosis and autophagy under cisplatin injury. Taken together, we demonstrate that, for the first time, that HMGCR is expressed in the cochlear. Furthermore, HMGCR exerts protective benefit on auditory cells against cisplatin-mediated injury stimulated by ROS, culminating in regulation of p38 MAPK-dependent apoptosis and autophagy.

Safety and efficacy of precision hepatectomy in the treatment of primary liver cancer.

BACKGROUND: The aim of this study was to investigate the safety and efficacy of precision hepatectomy in the treatment of primary liver cancer. METHODS: An randomized controlled trial of 98 patients with primary liver cancer admitted to our hospital from February 2020 to February 2021 were analyzed for the study, and they were divided into 49 cases each in the control group (conventional hepatectomy) and the study group (precision hepatectomy) according to the different surgical methods. The surgical condition, complications and follow-up results of the two groups were counted, and the liver function and immune function of the two groups were observed before and 1 week after surgery. RESULTS: The operation time, intraoperative bleeding, hospitalization time and anal venting time in the study group were less than those in the control group (P < 0.05). One week after surgery, AST, TBiL, ALT and ALB levels decreased, with in the study group significantly higher than those in the control group (P < 0.05); CD4+, CD3 + and CD4+/CD8 + levels were significantly higher in the study group (P < 0.05). The incidence of complications in the study group was significantly lower than that in the control group (P < 0.05). After 2 years of follow-up, the recurrence rate and mortality rate of the study group were lower than those of the control group (P < 0.05); the difference was not statistically significant when comparing the metastasis rate between the two groups (P > 0.05). CONCLUSION: Precision hepatectomy can effectively treat primary liver cancer with high safety and could be promoted in clinical practice.

Genome-Wide Identification and Expression Analysis of Calmodulin and Calmodulin-like Genes, Revealing CaM3 and CML13 Participating in Drought Stress in Phoebe bournei.

Calmodulin (CaM) and calmodulin-like (CML) proteins are major Ca2+ sensors involved in the regulation of plant development and stress responses by converting Ca2+ signals into appropriate cellular responses. However, characterization and expression analyses of CaM/CML genes in the precious species, Phoebe bournei, remain limited. In this study, five PbCaM and sixty PbCML genes were identified that only had EF-hand motifs with no other functional domains. The phylogenetic tree was clustered into 11 subgroups, including a unique clade of PbCaMs. The PbCaMs were intron-rich with four EF-hand motifs, whereas PbCMLs had two to four EF-hands and were mostly intronless. PbCaMs/CMLs were unevenly distributed across the 12 chromosomes of P. bournei and underwent purifying selection. Fragment duplication was the main driving force for the evolution of the PbCaM/CML gene family. Cis-acting element analysis indicated that PbCaMs/CMLs might be related to hormones, growth and development, and stress response. Expression analysis showed that PbCaMs were generally highly expressed in five different tissues and under drought stress, whereas PbCMLs showed specific expression patterns. The expression levels of 11 candidate PbCaMs/CMLs were responsive to ABA and MeJA, suggesting that these genes might act through multiple signaling pathways. The overexpression of PbCaM3/CML13 genes significantly increased the tolerance of yeast cells to drought stress. The identification and characterization of the CaM/CML gene family in P. bournei laid the foundation for future functional studies of these genes.

Cyanidin-3-O-glucoside Contributes to Leaf Color Change by Regulating Two bHLH Transcription Factors in Phoebe bournei.

Anthocyanins produce different-colored pigments in plant organs, which provide ornamental value. Thus, this study was conducted to understand the mechanism of anthocyanin synthesis in ornamental plants. Phoebe bournei, a Chinese specialty tree, has high ornamental and economic value due to its rich leaf color and diverse metabolic products. Here, the metabolic data and gene expression of red P. bournei leaves at the three developmental stages were evaluated to elucidate the color-production mechanism in the red-leaved P. bournei species. First, metabolomic analysis identified 34 anthocyanin metabolites showing high levels of cyanidin-3-O-glucoside (cya-3-O-glu) in the S1 stage, which may suggest that it is a characteristic metabolite associated with the red coloration of the leaves. Second, transcriptome analysis showed that 94 structural genes were involved in anthocyanin biosynthesis, especially flavanone 3'-hydroxy-lase (PbF3'H), and were significantly correlated with the cya-3-O-glu level. Third, K-means clustering analysis and phylogenetic analyses identified PbbHLH1 and PbbHLH2, which shared the same expression pattern as most structural genes, indicating that these two PbbHLH genes may be regulators of anthocyanin biosynthesis in P. bournei. Finally, overexpression of PbbHLH1 and PbbHLH2 in Nicotiana tabacum leaves triggered anthocyanin accumulation. These findings provide a basis for cultivating P. bournei varieties that have high ornamental value.

Equivalent magnitude-dependent discomfort under vertical vibration up to 100 Hz.

The effect of vibration magnitude on frequency-dependence of discomfort of human body is always overlooked with respect to the comfort equivalence contours, particularly for high-magnitude vibration in wideband frequency. In this study, the magnitude effect of vertical vibration on discomfort of human body is investigated experimentally. Nineteen male subjects are involved in the jury test of vibration discomfort in the vertical direction with 2-5 m/s2 in magnitude up to 100 Hz. It is shown that the growth rate of discomfort may exceed 1 due to the high-magnitude vibration employed. In this condition that the rate varies around 1, the Stevens' power law is not capable to properly represent the relationship between the subjective discomfort and the vibration magnitude. It means the equivalent comfort contours are not only dependent on the frequency range but also related to the vibration magnitude. Frequency weightings of vibration discomfort are influenced by the excitation magnitude. Practitioner summary: The occupant comfort to vertical whole-body vibration is affected by vibration magnitude. This study provides the effect of vibration magnitude on frequency-dependence of discomfort to whole-body vibration. It is suggested to propose variable frequency weightings for vibration discomfort evaluation under different magnitudes to achieve better comfort design.

Torque response of seated human body to sinusoidal lateral and roll dual-axis vibration.

The biodynamic response of 14 subjects to sinusoidal dual-axis vibration in lateral and roll directions is studied. The root mean square of human response is detected by measuring the torque at the seat pan. The effects of phase difference, magnitude, and frequency on the biodynamic responses are investigated. The consistency between human responses to dual-axis and single-axis is studied. With increasing phase difference, human response is found to reach the maximum when the vibrations are anti-phase and then decrease to the minimum when they are in-phase. Besides, the dominance of the lateral excitation is confirmed in the dual-axis vibration. Finally, the principle of equivalence between lateral-roll dual-axis vibration and roll single-axis vibration is established. With the equivalence method, the biodynamic characteristics of the human body to multi-axis vibration are expected to be measured and represented with a much simpler test and dynamic model.Practitioner summary: Proposed equivalence uses one index to evaluate the compound discomfort caused by the roll and lateral vibration. Overestimation of discomfort due by summing the effects of them calculated separately can be avoided. After the equivalence, evaluation of discomfort and modelling of the human body can be carried out only in roll direction.

The tomato CONSTANS-LIKE protein SlCOL1 regulates fruit yield by repressing SFT gene expression.

BACKGROUND: CONSTANS (CO) and CONSTANS-LIKE (COL) transcription factors have been known to regulate a series of cellular processes including the transition from the vegetative growth to flower development in plants. However, their role in regulating fruit yield in tomato is poorly understood. RESULT: In this study, the tomato ortholog of Arabidopsis CONSTANS, SlCOL1, was shown to play key roles in the control of flower development and fruit yield. Suppression of SlCOL1 expression in tomato was found to lead to promotion of flower and fruit development, resulting in increased tomato fruit yield. On the contrary, overexpression of SlCOL1 disturbed flower and fruit development, and significantly reduced tomato fruit yield. Genetic and biochemical evidence indicated that SlCOL1 controls inflorescence development by directly binding to the promoter region of tomato inflorescence-associated gene SINGLE-FLOWER TRUSS (SFT) and negatively regulating its expression. Additionally, we found that SlCOL1 can also negatively regulate fruit size in tomato. CONCLUSIONS: Tomato SlCOL1 binds to the promoter of the SFT gene, down-regulates its expression, and plays a key role in reducing the fruit size.

Disruption of C/EBPß-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain.

BACKGROUND: Growing evidence shows that C-Type Lectin Domain Containing 7A (Clec7a) may be involved into neuroinflammatory injury of various neurological diseases. However, its roles in neuropathic pain remain unclear. METHODS: A chronic constriction injury (CCI) rat model was constructed, and gene expression profilings in spinal cord tissues of CCI-insulted rats were detected by both microarray and RNA-seq studies. A series of bioinformatics analyses identified C/EBPß-Clec7a to be a candidate axis involved into neuropathic pain. Then, its roles in mechanical allodynia, and pathological and molecular changes during CCI progression were determined by various gain-of-function and loss-of-function experiments in vivo and in vitro. RESULTS: Significant upregulation of Clec7a at both mRNA and protein levels were verified in spinal cord tissues of CCI-insulted rats. Clec7a knockdown markedly attenuated CCI-induced mechanical allodynia, obstructed Syk, ERK and JNK phosphorylation, inhibited NLRP3 inflammasome and caspase-1 activation, GSDMD cleavage, and consequently reduced the release of pro-inflammatory cytokines (all P < 0.05). Mechanically, the rat Clec7a promoter was predicted to bind with transcription factor C/EBPß, confirmed by Luciferase assay and ChIP-qPCR. Both in vivo and in vitro assays demonstrated that C/EBPß knockdown significantly suppressed CCI- or LPS/ATP-induced Clec7a upregulation, and subsequently reduced Syk, ERK and JNK phosphorylation, NLRP3 oligomerization, caspase-1 activation, GSDMD expression and pyroptosis, which were markedly reversed by the co-transfection of Clec7a expression vector. CONCLUSIONS: This pre-clinical investigation reveals that C/EBPß-Clec7a axis may be a potential target for relieving neuropathic pain through alleviating neuroinflammation, paving its way for clinical translation as a promising approach for neuropathic pain therapy.