CsRAXs negatively regulate leaf size and fruiting ability through auxin glycosylation in cucumber.

Leaves are the main photosynthesis organ that directly determines crop yield and biomass. Dissecting the regulatory mechanism of leaf development is crucial for food security and ecosystem turn-over. Here, we identified the novel function of R2R3-MYB transcription factors CsRAXs in regulating cucumber leaf size and fruiting ability. Csrax5 single mutant exhibited enlarged leaf size and stem diameter, and Csrax1/2/5 triple mutant displayed further enlargement phenotype. Overexpression of CsRAX1 or CsRAX5 gave rise to smaller leaf and thinner stem. The fruiting ability of Csrax1/2/5 plants was significantly enhanced, while that of CsRAX5 overexpression lines was greatly weakened. Similarly, cell number and free auxin level were elevated in mutant plants while decreased in overexpression lines. Biochemical data indicated that CsRAX1/5 directly promoted the expression of auxin glucosyltransferase gene CsUGT74E2. Therefore, our data suggested that CsRAXs function as repressors for leaf size development by promoting auxin glycosylation to decrease free auxin level and cell division in cucumber. Our findings provide new gene targets for cucumber breeding with increased leaf size and crop yield.

Knowledge, Attitudes and Practices Towards Psoriasis Among Patients and Their Family Members.

Purpose: KAP studies serve to enhance health consciousness and furnish foundational data for appraising, strategizing, and enacting disease management and prejudice eradication initiatives. There remains a dearth of published studies elucidating the dimensions of knowledge, attitudes, and practices among psoriasis patients in China. To investigate the knowledge, attitudes and practices (KAP) towards psoriasis among patients and their family members in Northern China. Methods: This web-based, cross-sectional study was conducted among psoriasis patients and their family members through a self-administered questionnaire. Results: Among patients (n=260), their mean KAP scores were 9.76±5.69 (range: 0-19), 35.64±11.48 (range: 14-70), and 56.73±10.98 (range: 16-80), respectively. Among family members (n=237), their mean KAP scores were 11.93±5.34 (range: 0-19), 35.80±4.34 (range: 8-40), and 37.04±4.38 (range: 8-40), respectively. Structural equation modeling (SEM) analysis for patients indicated significant and negative path relations between knowledge and attitudes (ß=-2.271, P<0.001), and between knowledge and practice (ß=-0.398, P<0.001). Extended SEM analysis, which divides knowledge into K1, K2, and K3 parts, showed negative path relations between K3 and attitude (ß=-1.300, P=0.002), between attitude and practice (ß=-0.634, P<0.001). Moreover, SEM for family members showed positive path relations between knowledge and attitude (ß=1.536, P<0.001), between attitude and practice (ß=0.682, P<0.001). Conclusion: Patients in Northern China demonstrated insufficient knowledge, negative attitude, and proactive practice, while their family members had insufficient knowledge, positive attitude, and proactive practice toward psoriasis. It is recommended to implement educational interventions addressing knowledge gaps among patients and families.

Deep learning-based arterial subtraction images improve the detection of LR-TR algorithm for viable HCC on extracellular agents-enhanced MRI.

PURPOSE: To determine the role of deep learning-based arterial subtraction images in viability assessment on extracellular agents-enhanced MRI using LR-TR algorithm. METHODS: Patients diagnosed with HCC who underwent locoregional therapy were retrospectively collected. We constructed a deep learning-based subtraction model and automatically generated arterial subtraction images. Two radiologists evaluated LR-TR category on ordinary images and then evaluated again on ordinary images plus arterial subtraction images after a 2-month washout period. The reference standard for viability was tumor stain on the digital subtraction hepatic angiography within 1 month after MRI. RESULTS: 286 observations of 105 patients were ultimately enrolled. 157 observations were viable and 129 observations were nonviable according to the reference standard. The sensitivity and accuracy of LR-TR algorithm for detecting viable HCC significantly increased with the application of arterial subtraction images (87.9% vs. 67.5%, p < 0.001; 86.4% vs. 75.9%, p < 0.001). And the specificity slightly decreased without significant difference when the arterial subtraction images were added (84.5% vs. 86.0%, p = 0.687). The AUC of LR-TR algorithm significantly increased with the addition of arterial subtraction images (0.862 vs. 0.768, p < 0.001). The arterial subtraction images also improved inter-reader agreement (0.857 vs. 0.727). CONCLUSION: Extended application of deep learning-based arterial subtraction images on extracellular agents-enhanced MRI can increase the sensitivity of LR-TR algorithm for detecting viable HCC without significant change in specificity.

The AGAMOUS-LIKE 16-GENERAL REGULATORY FACTOR 1 module regulates axillary bud outgrowth via catabolism of abscisic acid in cucumber.

Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.

Unlocking the Transcriptional Control of NCAPG in Bovine Myoblasts: CREB1 and MYOD1 as Key Players.

Muscle formation directly determines meat production and quality. The non-SMC condensin I complex subunit G (NCAPG) is strongly linked to the growth features of domestic animals because it is essential in controlling muscle growth and development. This study aims to elucidate the tissue expression level of the bovine NCAPG gene, and determine the key transcription factors for regulating the bovine NCAPG gene. In this study, we observed that the bovine NCAPG gene exhibited high expression levels in longissimus dorsi and spleen tissues. Subsequently, we cloned and characterized the promoter region of the bovine NCAPG gene, consisting of a 2039 bp sequence, through constructing the deletion fragment double-luciferase reporter vector and site-directed mutation-identifying core promoter region with its key transcription factor binding site. In addition, the key transcription factors of the core promoter sequence of the bovine NCAPG gene were analyzed and predicted using online software. Furthermore, by integrating overexpression experiments and the electrophoretic mobility shift assay (EMSA), we have shown that cAMP response element binding protein 1 (CREB1) and myogenic differentiation 1 (MYOD1) bind to the core promoter region (-598/+87), activating transcription activity in the bovine NCAPG gene. In conclusion, these findings shed important light on the regulatory network mechanism that underlies the expression of the NCAPG gene throughout the development of the muscles in beef cattle.

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF-α and IL-23p19 bioactivities.

BACKGROUND: Inflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non-response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF-α (tumour necrosis factor-α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond. METHODS: We designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage-expressed membrane TNF-α (hmTNF-α) and IL-23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb-Fc.  Our study encompassed in vitro and in vivo characterization of BsNb and BsNb-Fc. RESULTS: BsNb-Fc exhibited an improved serum half-life, targeting capability and effector function than BsNb. It's demonstrated that BsNb-Fc exhibited superior anti-inflammatory effects compared to the anti-TNF-α mAb (infliximab, IFX) combined with anti-IL-12/IL-23p40 mAb (ustekinumab, UST) by Transwell co-culture assays. Notably, in murine models of acute colitis brought on by 2,4,6-trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb-Fc effectively alleviated colitis severity. Additionally, BsNb-Fc outperformed the IFX&UST combination in TNBS-induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS. CONCLUSION: These findings highlight an enhanced efficacy and improved biostability of BsNb-Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF-α inhibition. KEY POINTS: A bispecific nanobody (BsNb) was created to target TNF-α and IL-23p19, exhibiting high affinity and remarkable stability. BsNb-Fc inhibited the release of cytokines in CD4+T cells during co-culture experiments. BsNb-Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination.

GLABRA 2 regulates ETHYLENE OVERPRODUCER 1 accumulation during nutrient deficiency-induced root hair growth.

Root hairs (RHs), extensive structures of root epidermal cells, are important for plant nutrient acquisition, soil anchorage, and environmental interactions. Excessive production of the phytohormone ethylene (ET) leads to substantial root hair growth, manifested as tolerance to plant nutrient deficiencies. However, the molecular basis of ET production during root hair growth in response to nutrient starvation remains unknown. Herein, we found that a critical transcription factor, GLABRA 2 (GL2), inhibits ET production during root hair growth in Arabidopsis (Arabidopsis thaliana). GL2 directly binds to the promoter of the gene encoding ET OVERPRODUCER 1 (ETO1), one of the most important ET-production-regulation factors, in vitro and in vivo, and then regulates the accumulation and function of ETO1 in root hair growth. The GL2-regulated-ETO1 module is required for promoting root hair growth under nitrogen, phosphorus, or potassium deficiency. Genome-wide analysis revealed numerous genes, such as ROOT HAIR DEFECTIVE 6-LIKE 4, ETHYLENE-INSENSITIVE 3-LIKE 2, ROOT HAIR SPECIFIC 13, are involved in the GL2-regulated-ETO1 module. Our work reveals a key transcription mechanism in the control of ET production during root hair growth under three major nutrient deficiencies.

Interactions and effects of a stannous-containing sodium fluoride dentifrice on oral pathogens and the oral microbiome.

Numerous studies have investigated the effects of stannous ions on specific microbes and their efficacy in reducing dental plaque. Nonetheless, our understanding of their impact on the oral microbiome is still a subject of ongoing exploration. Therefore, this study sought to evaluate the effects of a stannous-containing sodium fluoride dentifrice in comparison to a zinc-containing sodium fluoride dentifrice and a control group on intact, healthy oral biofilms. Utilizing the novel 2bRAD-M approach for species-resolved metagenomics, and FISH/CLSM with probes targeting periodontal and caries associated species alongside Sn2+ and Zn2+ ions, we collected and analyzed in situ biofilms from 15 generally healthy individuals with measurable dental plaque and treated the biofilms with dentifrices to elucidate variations in microbial distribution. Although significant shifts in the microbiome upon treatment were not observed, the use of a stannous-containing sodium fluoride dentifrice primarily led to an increase in health-associated commensal species and decrease in pathogenic species. Notably, FISH/CLSM analysis highlighted a marked reduction in representative species associated with periodontitis and caries following treatment with the use of a stannous-containing sodium fluoride dentifrice, as opposed to a zinc-containing sodium fluoride dentifrice and the control group. Additionally, Sn2+ specific intracellular imaging reflected the colocalization of Sn2+ ions with P. gingivalis but not with other species. In contrast, Zn2+ ions exhibited non-specific binding, thus suggesting that Sn2+ could exhibit selective binding toward pathogenic species. Altogether, our results demonstrate that stannous ions could help to maintain a healthy oral microbiome by preferentially targeting certain pathogenic bacteria to reverse dysbiosis and underscores the importance of the continual usage of such products as a preventive measure for oral diseases and the maintenance of health.

Bisphenol chemicals in colostrum from Shanghai, China during 2006-2019: Concentration, temporal variation, and potential influence on birth parameters.

Bisphenol A (BPA) and its alternatives bisphenol S (BPS) and bisphenol F (BPF) are identified as endocrine disruptors that have negative impacts on infant growth. Their temporal variations in human milk and potential effects on fetal growth are not well known. In this study, colostrum collecting at four time points between 2006 and 2019 and paired urine in 2019 from Shanghai, China, were analyzed for eight bisphenols. The total concentrations in colostrum in 2019 were up to 3.43 ng/mL, with BPA being dominant, followed by BPS and BPF. BPA levels in colostrum noticeably decreased from 2010 to 2013. Additionally, obvious percentage changes in bisphenols were observed in 2019. The BPA concentrations in paired colostrum and urine were not significantly correlated. High levels of BPA in colostrum were linked to a significant reduction in birth head circumference in 2019 (p = 0.031). BPA and BPS in colostrum might have similar negative effect on fetal growth in 2019, but these effects were generally non-significant. Further studies are needed to testify the potential impact. The hazard indexes for infants in the first week of life were below 1, suggesting no obvious health risks. However, the high contribution from BPA still warrants further attention.

TL1A promotes metastasis and EMT process of colorectal cancer.

Background: Metastasis is the major problem of colorectal cancer (CRC) and is correlated with the high mortality. Tumor necrosis factor-like cytokine 1A (TL1A) is a novel regulatory factor for inflammatory diseases. This work aimed to investigate the role of TL1A in CRC metastasis. Method: AOM/DSS-induced mouse model, xenograft tumor model and metastasis murine model were established to mimic the colitis-associated CRC and investigate CRC growth and metastasis in vivo. Colon tissues were assessed by hematoxylin/eosin (HE) staining and immunohistochemistry (IHC). CRC cell metastasis in vivo was observed using in vivo imaging system (IVIS). Cell viability and proliferation were examined using cell counting kit 8 (CCK-8) and EdU experiments. The expression of tumor growth factor ß (TGFß) and metastatic biomarkers were detected using western blotting experiment. The in vitro cell metastasis was measured by Transwell. Results: Knockdown of TL1A notably suppressed the generation of colonic tumors in azoxymethane/dextran sodium sulfate (AOM/DSS) model, suppressed in vivo CRC cell growth, as well as lung and liver metastasis. The inflammation response and inflammatory cell infiltration in tumor sites were decreased by TL1A depletion. The in vitro CRC cell growth and metastasis was also suppressed by shTL1A, along with altered expression of epithelial mesenchymal transition (EMT) biomarkers. TL1A depletion suppressed the level of the TGF-ß1 receptor (TßRI) and phosphorylation of Smad3 in CRC cells. Stimulation with TGF-ß recovered the CRC cell migration and invasion that suppressed by shTL1A. Conclusion: Our work implicated TL1A as a promoter of CRC generation and metastasis and defines TGF-ß/Smad3 signaling as mediator of TL1A-regualated CRC cell metastasis.

[Trametenolic acid inhibits migration and invasion of hepatocellular carcinoma HepG2.2.15 cells via RhoC/ROCK1 pathway].

This study investigated the effect of trametenolic acid(TA) on the migration and invasion of human hepatocellular carcinoma HepG2.2.15 cells by using Ras homolog gene family member C(RhoC) as the target and probed into the mechanism, aiming to provide a basis for the utilization of TA. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of HepG2.2.15 cells exposed to TA, and scratch and Transwell assays to examine the cell migration and invasion. The pull down assay was employed to determine the impact of TA on RhoC GTPase activity. Western blot was employed to measure the effect of TA on the transport of RhoC from cytoplasm to cell membrane and the expression of RhoC/Rho-associated kinase 1(ROCK1)/myosin light chain(MLC)/matrix metalloprotease 2(MMP2)/MMP9 pathway-related proteins. RhoC was over-expressed by transient transfection of pcDNA3.1-RhoC. The changes of F-actin in the cytoskeleton were detected by Laser confocal microscopy. In addition, the changes of cell migration and invasion, expression of proteins in the RhoC/ROCK1/MLC/MMP2/MMP9 pathway, and RhoC GTPase activity were detected. The subcutaneously transplanted tumor model of BALB/c nude mice and the low-, medium-, and high-dose(40, 80, and 120 mg·kg~(-1), respectively) TA groups were established and sorafenib(20 mg·kg~(-1)) was used as the positive control. The tumor volume and weight in each group were measured, and the expression of related proteins in the tumor tissue was determined by Western blot. The results showed that TA inhibited the proliferation of HepG2.2.15 cells in a concentration-dependent manner, with the IC_(50) of 66.65 and 23.09 µmol·L~(-1) at the time points of 24 and 48 h, respectively. The drug administration groups had small tumors with low mass. The tumor inhibition rates of sorafenib and low-, medium-and high-dose TA were 62.23%, 26.48%, 55.45%, and 62.36%, respectively. TA reduced migrating and invading cells and inhibited RhoC protein expression and RhoC GTPase activity in a concentration-dependent manner, dramatically reducing RhoC and membrane-bound RhoC GTPase. The expression of ROCK1, MLC, p-MLC, MMP2, and MMP9 downstream of RhoC can be significantly inhibited by TA, as confirmed in both in vitro and in vivo experiments. After HepG2.2.15 cells were transfected with pcDNA3.1-RhoC to overexpress RhoC, TA down-regulated the protein levels of RhoC, ROCK1, MLC, p-MLC, MMP2, and MMP9 and decreased the activity of RhoC GTPase, with the inhibition level comparable to that before overexpression. In summary, TA can inhibit the migration and invasion of HepG2.2.15 cells. It can inhibit the RhoC/ROCK1/MLC/MMP2/MMP9 signaling pathway by suppressing RhoC GTPase activity and down-regulating RhoC expression. This study provides a new idea for the development of autophagy modulators targeting HSP90α to block the proliferation and inhibit the invasion and migration of hepatocellular carcinoma cells via multiple targets of active components in traditional Chinese medicines.

In Vitro Profiling of Toxicity Effects of Different Environmental Factors on Skin Cells.

The skin is constantly exposed to a variety of environmental threats. Therefore, the influence of environmental factors on skin damage has always been a matter of concern. This study aimed to investigate the cytotoxic effects of different environmental factors, including cooking oil fumes (COFs), haze (PM2.5), and cigarette smoke (CS), on epidermal HaCaT cells and dermal fibroblast (FB) cells. Cell viability, intracellular reactive oxygen species (ROS) generation, inflammatory cytokine levels, and collagen mRNA expression were used as toxicity endpoints. Additionally, the effects of ozone (O3) on cell viability and release of inflammatory cytokines in 3D epidermal cells were also examined. The results showed that the organic extracts of CS, COFs, and PM2.5 significantly inhibited the viability of HaCaT and FB cells at higher exposure concentrations. These extracts also increased intracellular ROS levels in FB cells. Furthermore, they significantly promoted the release of inflammatory cytokines, such as IL-1α and TNF-α, in HaCaT cells and down-regulated the mRNA expression of collagen I, III, IV, and VII in FB cells. Comparatively, SC organic extracts exhibited stronger cytotoxicity to skin cells compared to PM2.5 and COFs. Additionally, O3 at all test concentrations significantly inhibited the viability of 3D epidermal cells in a concentration-dependent manner and markedly increased the levels of TNF-α and IL-1α in 3D epidermal cells. These findings emphasize the potential cytotoxicity of COFs, PM2.5, CS, and O3 to skin cells, which may lead to skin damage; therefore, we should pay attention to these environmental factors and take appropriate measures to protect the skin from their harmful effects.

The learning curve of the MS-TRAM/DIEP breast reconstruction by dual-trained breast surgeons.

BACKGROUND: Breast cancer surgeries involving MS-TRAM/DIEP breast reconstruction has traditionally been collaborative efforts between breast surgeons and plastic surgeons. However, in our institution, this procedure is performed by dual-trained breast surgeons who are proficient in both breast surgery and MS-TRAM/DIEP breast reconstruction. This study aims to provide insights into the learning curve associated with this surgical approach. MATERIALS AND METHODS: We included eligible breast cancer patients who underwent MS-TRAM/DIEP breast reconstruction by dual-trained breast surgeons between 2015 and 2020 at our institution. We present the learning curve of this surgical approach, with a focus on determining factors affecting flap harvesting time, surgery time, and ischemic time. Additionally, we assessed the surgical complication rates. RESULTS: A total of 147 eligible patients were enrolled in this study. Notably, after 30 cases, a statistically significant reduction of 1.7 h in surgery time and 21 min in ischemic time was achieved, signifying the attainment of a plateau in the learning curve. And the major and minor complications were comparable between the early and after 30 cases. CONCLUSION: This study explores the learning curve and feasibility experienced by dual-trained breast surgeons in performing MS-TRAM/DIEP breast reconstruction. TRIAL REGISTRATION: NCT05560633.

The influence of sleep factors and dietary habits on the disease pattern of ulcerative colitis patients with long and short disease courses - a multicentre cross-sectional analysis.

BACKGROUND: Ulcerative colitis (UC) is a disease characterized by chronic relapsing-remitting inflammatory disorders and is associated with environmental changes. AIM: To explore the disease patterns of Chinese UC patients and to determine controllable related environmental factors. METHODS: This multicentre cross-sectional study was performed using a questionnaire survey. Data on clinical characteristics and environmental factors were collected. Patients with a disease course ≥5 years were defined as the long course group, and those with a disease course < 5 years were defined as the short course group. RESULTS: A total of 588 effective questionnaires were collected. The proportion of the chronic continuous pattern was the highest among patients with a long disease course (46.8%), and in patients with a short disease course, the proportion of the active to remission pattern was the highest (53.3%). In patients with a long disease course, a higher proportion of patients with adequate sleep was found in the active to remission pattern than in the chronic intermittent (72.1% vs. 43.3%, p = 0.008) and chronic continuous (72.1% vs. 52.4%, p = 0.016) patterns. In patients with a short disease course, the frequency of shellfish and shrimp was higher in the chronic continuous pattern group than in the active to remission pattern group (P = 0.001 and 0.017 respectively). CONCLUSIONS: For early diagnosis patients, dietary guidance should be actively carried out. With the prolongation of the disease course, attention should be given to the sleep quality of patients.

1.UC exhibits various disease patterns, which may be associated with differences in patient prognosis and treatment response.2.Environmental factors, especially sleep and dietary factors, correlated strongly with disease patterns, which varied in different disease courses.3.Early diagnosis patients should receive active dietary guidance, while patients with a prolonged disease course require attention to their sleep quality and appropriate drug interventions when necessary.

Changes of putative pathogenic species within the water bacterial community in large-scale drinking water treatment and distribution systems.

Although the management of microbes in drinking water is of paramount importance for public health, there remain challenges in comprehensively examining pathogenic bacteria in the water supply system at the species level. In this study, high-throughput sequencing of nearly full-length 16S rRNA genes was performed to investigate the changes of the water bacterial community in three large-scale drinking water treatment plants (DWTPs) and their corresponding distribution systems during winter and summer. Our findings revealed significant differences in the bacterial community structure between winter and summer water samples for each DWTP and its distribution management area (DMA). In the groundwater-fed DWTP, selective enrichment of mycobacterial species was observed in both seasons, and the subsequent DMA also exhibited strong selection for specific mycobacterial species. In one of the surface water-fed DWTPs, certain Legionella species present in the source water in winter were selectively enriched in the bacterial community after pre-oxidation, although they were susceptible to the subsequent purification steps. A variety of putative pathogenic species (n = 83) were identified based on our pathogen identification pipeline, with the dominant species representing opportunistic pathogens commonly found in water supply systems. While pathogen removal primarily occurred during the purification processes of DWTPs, especially for surface water-fed plants, the relative abundance of pathogenic bacteria in the DMA water flora was lower than that in the DWTP effluent flora, indicating a diminished competitiveness of pathogens within the DMA ecosystem.

RAB27B-regulated exosomes mediate LSC maintenance via resistance to senescence and crosstalk with the microenvironment.

The fate of leukaemia stem cells (LSCs) is determined by both their inherent mechanisms and crosstalk with their niches. Although LSCs were confirmed to be eradicated by restarting senescence, the specific key regulators of LSC resistance to senescence and remodelling of the niche to obtain a microenvironment suitable for stemness remain unknown. Here, we found that RAB27B, a gene regulating exosome secretion, was overexpressed in LSCs and associated with the poor prognosis of acute myeloid leukaemia (AML) patients. The increased RAB27B in LSCs prevented their senescence and maintained their stemness in vitro and in vivo. Mechanically, the increased RAB27B expression in LSCs selectively promoted the loading and release of exosomes rich in senescence-inducing proteins by direct combination. Furthermore, RAB27B-regulated LSC-derived exosomes remodelled the niche and induced senescence of mesenchymal stem cells (MSCs) with increased RAB27B expression ex vivo and in vivo. The increased RAB27B in the senescent MSCs conversely promoted LSC maintenance ex vivo and in vivo via selective excretion of exosomes rich in stemness-promoting proteins. Therefore, we identified the specifically increased RAB27B in LSCs and their educated senescent MSCs as a hub molecule for LSC resistance to senescence and maintenance through crosstalk with its niche via selective exosome excretion.

The exocyst subunit CsExo70B promotes both fruit length and disease resistance via regulating receptor kinase abundance at plasma membrane in cucumber.

Plant defence against pathogens generally occurs at the expense of growth and yield. Uncoupling the inverse relationship between growth and defence is of great importance for crop breeding, while the underlying genes and regulatory mechanisms remain largely elusive. The exocytosis complex was shown to play an important role in the trafficking of receptor kinases (RKs) to the plasma membrane (PM). Here, we found a Cucumis sativus exocytosis subunit Exo70B (CsExo70B) regulates the abundance of both development and defence RKs at the PM to promote fruit elongation and disease resistance in cucumber. Knockout of CsExo70B resulted in shorter fruit and susceptibility to pathogens. Mechanistically, CsExo70B associates with the developmental RK CsERECTA, which promotes fruit longitudinal growth in cucumber, and contributes to its accumulation at the PM. On the other side, CsExo70B confers to the spectrum resistance to pathogens in cucumber via a similar regulatory module of defence RKs. Moreover, CsExo70B overexpression lines showed an increased fruit yield as well as disease resistance. Collectively, our work reveals a regulatory mechanism that CsExo70B promotes both fruit elongation and disease resistance by maintaining appropriate RK levels at the PM and thus provides a possible strategy for superior cucumber breeding with high yield and robust pathogen resistance.

Flexible molecularly imprinted fiber library for the metabolic analysis of bisphenol F and ecological risk evaluation.

Bisphenol F (BPF) has evoked global attentions due to its ubiquity and detrimental effects. Herein, a flexible molecularly imprinted fiber library was firstly proposed for the metabolic analysis of BPF in aquatic ecosystems. The library includes flexible single fibers and fiber arrays to precisely identify BPF and its metabolites with a wide range of polarities. Compared to commercial polyacrylate, the performance increased 11.56-570.98-fold. The adsorption capacity and the LogKow value were positively related. These arrays were used for the acquisition of environmental metabolomics data from aquatic ecosystems. In-depth data analysis showed that risk quotient was lower than 0.76, and bioaccumulation factor was lower than 2000 L/kg. Distribution concentration of BPF and its metabolites changed seasonally, and accumulation in sediment was much larger than that in surface water and hydrobionts. The risk is gradually increasing in sediment, but it does not reach high risk. The likelihood of bioaccumulation of parent compounds was greater than its metabolites. The library can be used in the metabolic diagnosis of pollutants with a broad range of polarities, providing a new method to acquire data for further ecological risk assessment, and offering a revolutionary strategy for environmental metabolomics investigation in aquatic ecosystems.

The work experience of male nursing teachers in Chinese universities: a phenomenological study.

Background: With the increase in the number of male nursing staff, more and more highly educated male nursing staff are joining the nursing higher education industry. Nevertheless, male nursing teachers in China are still a very small group in the education industry, but they have made important contributions to nursing education in China. Work experience is a key factor in the stability of the professional team and the quality of education. However, there is little research on the professional feelings of Chinese male nursing teachers. Objective: Explore the true feelings of male nursing teachers in Chinese universities about their work, understand their actual work difficulties, their sources of work stress and methods of coping with stress under the Chinese cultural background, and combine their professional expectations to provide ways to solve these problems, and help male nursing educators better apply nursing education work. Methods: This study uses an interpretive and exploratory qualitative research design method, in which the participants of male nursing teachers are selected from 30 universities with nursing majors in Zhejiang Province by the method of purpose sampling, and semi-structured in-depth interviews were used to collect data. A Van Manen process was used for data analysis. The 10th respondents were saturated. Results: Five themes were extracted in this study, namely realistic difficulties of career, positive feelings of career, sources of occupational stress, coping methods for occupational stress, and career development expectations. Conclusions: Male nursing teachers in universities can actively adjust their thoughts and behaviors and face negative professional feelings due to gender factors. But they still need more comprehension and support from educational institutions and society. The support of leaders and universities can help them better adjust to professional development and maintain a rational and stable nursing teacher team.

Follicular fluid C3a-peptide promotes oocyte maturation through F-actin aggregation.

BACKGROUND: Immature cumulus-oocyte complexes are retrieved to obtain mature oocytes by in vitro maturation (IVM), a laboratory tool in reproductive medicine to obtain mature oocytes. Unfortunately, the efficiency of IVM is not satisfactory. To circumvent this problem, we therefore intended to commence with the composition of ovarian follicular fluid (FF), an important microenvironment influencing oocyte growth. It is well known that FF has a critical role in oocyte development and maturation. However, the components in human FF remain largely unknown, particularly with regard to small molecular peptides. RESULTS: In current study, the follicular fluid derived from human mature and immature follicles were harvested. The peptide profiles of FF were further investigated by using combined ultrafiltration and LC-MS/MS. The differential peptides were preliminary determined by performing differentially expressed analysis. Human and mouse oocyte culture were used to verify the influence of differential peptides on oocyte development. Constructing plasmids, cell transfecting, Co-IP, PLA etc. were used to reveal the detail molecular mechanism. The results from differentially expressed peptide as well as cultured human and mouse oocytes analyses showed that highly conserved C3a-peptide, a cleavage product of complement C3a, definitely affected oocytes development. Intriguingly, C3a-peptide possessed a novel function that promoted F-actin aggregation and spindle migration, raised the percentage of oocytes at the MII stage, without increasing the chromosome aneuploidy ratio, especially in poor-quality oocytes. These effects of C3a-peptide were attenuated by C3aR morpholino inhibition, suggesting that C3a-peptide affected oocytes development by collaborating with its classical receptor, C3aR. Specially, we found that C3aR co-localized to the spindle with ß-tubulin to recruit F-actin toward the spindle and subcortical region of the oocytes through specific binding to MYO10, a key regulator for actin organization, spindle morphogenesis and positioning in oocytes. CONCLUSIONS: Our results provide a new perspective for improving IVM culture systems by applying FF components and also provide molecular insights into the physiological function of C3a-peptide, its interaction with C3aR, and their roles in enabling meiotic division of oocytes.