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aims: To elucidate the roles of PRC2 and HDACs in cardiomyocyte hypertrophy. background: Postnatal cardiomyocytes respond to stress signals by hypertrophic growth and fetal gene reprogramming, which involves epigenetic remodeling mediated by histone methyltransferase polycomb repressive complex 2 (PRC2) and histone deacetylases (HDACs). However, it remains unclear to what extent these histone modifiers contribute to the development of cardiomyocyte hypertrophy. objective: To compare the dose-dependent effects of GSK126 and TSA, inhibitors of PRC2 and HDACs, respectively, on cardiomyocyte hypertrophy. method: Neonatal rat ventricular myocytes (NRVMs) were stimulated by phenylephrine (PE; 50μM) to induce hypertrophy in the presence or absence of the PRC2 inhibitor GSK126 or the HDACs inhibitor Trichostatin A (TSA). Histone methylation and acetylation were measured by Western blot. Cell size was determined by wheat germ agglutinin (WGA) staining. Cardiac hypertrophy markers were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). result: PE treatment induced the expression of cardiac hypertrophy markers, including natriuretic peptide A (Nppa), natriuretic peptide B (Nppb), and myosin heavy chain 7 (Myh7), in a time-dependent manner in NRVMs. Histone modifications, including H3K27me3, H3K9ac, and H3K27ac, were dynamically altered after PE treatment. Treatment with TSA and GSK126 dose-dependently repressed histone acetylation and methylation, respectively. Whereas TSA reversed the PE-induced cell size enlargement in a wide range of concentrations, cardiomyocyte hypertrophy was only inhibited by GSK126 at a higher dose (1μM). Consistently, TSA dose-dependently suppressed the induction of Nppa, Nppb, and Myh7/Myh6 ratio, while these indexes were only inhibited by GSK126 at 1μM. However, TSA, but not GSK126, caused pro-hypertrophic expression of pathological genes at the basal level. conclusion: Our data demonstrate diversified effects of TSA and GSK126 on PE-induced cardiomyocyte hypertrophy, and shed a light on the epigenetic reprogramming in the pathogenesis of cardiac hypertrophy. other: Our data systematically compared the effects of TSA and GSK126 on PE-induced cardiomyocyte hypertrophy, and demonstrate the concentration thresholds for their protective function.

Rubella is listed by the World Health Organization (WHO) as a disease that needs to be eliminated worldwide. The aim of this study was to understand the progress and challenges towards rubella elimination in Beijing, China, by analyzing molecular surveillance data combined with immunization and surveillance strategies as well as epidemiological data. With high immunization coverage under the 3-dose policy (8 months, 18 months, and 6 years) and supplementary immunization activities for the floating population, rubella incidence showed a downward trend since 2010, despite two epidemics that occurred in 2014-2015 and 2019. The reported rubella cases were generally concentrated in the age group of 15-34 years. Although citywide surveillance for congenital rubella syndrome (CRS) has been carried out since 2016, only one case has been confirmed by laboratory testing. Furthermore, molecular surveillance data showed that rubella viruses (RVs) circulating in Beijing during 2010-2020 were evidently heterogeneous; the domestic lineage 1E-L1 and multiple imported lineages, including 2B-L1, 1E-L2, and 2B-L2c, were identified in the last decade. Meanwhile, two lineage-related switches were determined, including the displacement of lineage 1E-L1 with lineage 2B-L1 around 2014 and the transition between lineage 2B-L1 and lineage 1E-L2 and 2B-L2c in 2018-2019. This RV transmission pattern was similar to that observed across the country, whereas lineages 1E-L1 and 2B-L2c were prevalent in Beijing for a shorter period. Overall, these results indicate the need to maintain routine immunization with rubella-containing vaccines, promote regular supplementaryimmunizationactivities, and enhance rubella and CRS surveillance even in order to accelerate rubella elimination in Beijing. Further, the existing immunization strategies must be optimized to further close the immunity gap.

In order to improve the impermeability of ordinary “cement–water glass” double-liquid grouting material, this study prepares a composite grouting material with sodium bentonite, cement, and water glass as the main materials, water-reducing agent, and early strength agent as activators. In this study, orthogonal tests were conducted using an L16(45) orthogonal table and the test results were analyzed using regression analysis. Using bentonite instead of partial cement, the experimental factors of the bentonite ratio, glass slurry ratio, water-reducing agent admixture, and early strength agent admixture were used to study the laws of single-factor and two-factor interactions on the initial apparent viscosity, setting time, and compressive strength of composite grouting materials. After obtaining the optimal ratio of composite grouting materials, the mechanism of formation of material strength and seepage resistance properties was revealed. The results show that the mass ratio of bentonite to cement and the mass ratio of water glass to slurry have a large effect on the material properties, and there is an interactive effect of several factors at the same time. The optimal ratio of the material is 28.42% water, 36.58% cement, 6.20% bentonite, 0.04% water-reducing agent, 0.9% early strength agent, and 27.85% water glass. The microstructural analysis shows that the denseness of the stone body structure is enhanced, and thus the strength and impermeability of the material are improved. This composite grouting material improves injectability and seepage resistance and is more suitable for underpinning grouting of weakly cemented soft rocks, but the ratio optimization method and model used in this study can be applied to other materials.

A modified separator for improving the electrochemical performance in Li-S batteries is fabricated by functional composites coating, comprised of MnO nanoflakes with rich oxygen vacancies and N doped carbon nanotubes (MnO-OVs/NCNTs). On the one hand, MnO as a polar material can anchor lithium polysulfides (LiPSs) on the interface via chemical bonding. In addition, introducing oxygen vacancies into MnO by heat treatment under a reducing atmosphere can regulate the electronic structure and provide extra active sites for further boosting the chemical adsorption capability of LiPSs, facilitating the redox reaction of LiPSs, as well as enhancing the electron transfer efficiency. On the other hand, the MnO-OVs/NCNTs layer is a barrier to block the LiPSs directly diffusing through the separator and acts as an upper collector to reduce the interface resistance reactivate the trapped sulfur species, thereby enhancing the sulfur utilization. Given these advantages, the MnO-OVs/NCNTs modified separator employed in Li-S batteries exhibit considerable capacity (1516 mAh g

We rationally designed and fabricated F-doped NTO with the morphology of hollow spheres (F-NTO HSs) compacted by interwoven nanoflakes.

The non-uniform aggregation of fast-diffused Li on an anode surface would aggravate its tip-effect-induced nucleation/growth, leading to the notorious dendrite growth in Li metal batteries (LMBs). Tuning the Li diffusion on the anode surface has been regarded previously as a mainstream method to induce its uniform deposition, while the diffusion of Li in the anode bulk is usually ignored. Here, conceptually different from the classic surface modification, we propose a molecular tunnelling strategy to construct atomic channels in graphite bulk, which enables the fast diffusion of superdense Li. Density functional theory calculations and ab initio molecular dynamics simulations prove that the bulk diffusion through atomic channels could become a new and dominating path. Its reversible and efficient diffusion has been further visualized by in situ transmission electron microscopy. As a result, when coupled with high-loading LiFePO4 cathodes (20 mg cm−2), a high areal capacity and 100% capacity retention are achieved over 370 cycles. Through this work a new strategy is developed based on the bulk-diffusion of superdense Li for dendrite-free LMBs, which can be pervasive in other high-performance energy storage systems.

Alloying Pt with transition metals can significantly improve the catalytic properties for the oxygen reduction reaction (ORR). However, the application of Pt-transition metal alloys in fuel cells is largely limited by poor long-term durability because transition metals can easily leach. In this study, we developed a nonmetallic doping approach and prepared a P-doped Pt catalyst with excellent durability for the ORR. Carbon-supported core-shell nanoparticles with a P-doped Pt core and Pt shell (denoted as PtPx@Pt/C) were synthesized via heat-treatment phosphorization of commercial Pt/C, followed by acid etching. Compositional analysis using electron energy loss spectroscopy and X-ray photoelectron spectroscopy clearly demonstrated that Pt was enriched in the near-surface region (approximately 1 nm) of the carbon-supported core-shell nanoparticles. Owning to P doping, the ORR specific activity and mass activity of the PtP1.4@Pt/C catalyst were as high as 0.62 mA cm−2 and 0.31 mA μgPt−1, respectively, at 0.90 V, and they were enhanced by 2.8 and 2.1 times, respectively, in comparison with the Pt/C catalyst. More importantly, PtP1.4@Pt/C exhibited superior stability with negligible mass activity loss (6% after 30000 potential cycles and 25% after 90000 potential cycles), while Pt/C lost 46% mass activity after 30000 potential cycles. The high ORR activity and durability were mainly attributed to the core-shell nanostructure, the electronic structure effect, and the resistance of Pt nanoparticles against aggregation, which originated from the enhanced ability of the PtP1.4@Pt to anchor to the carbon support. This study provides a new approach for constructing nonmetal-doped Pt-based catalysts with excellent activity and durability for the ORR.

Cobalt oxide (Co3O4) is currently suitable in energy storage applications because of its high capacity based on the conversion reaction mechanism. However, unmodified Co3O4 suffers from distinctly inferior rate capability and poor cycling stability. On the basis of the aforementioned considerations and density functional theory (DFT) simulations, the three-dimensional hierarchical porous structure (HPS) ultrasmall Co3O4 anchored into ionic liquid (IL) modified graphene oxide (GO) has been successfully prepared (ultrasmall/Co3O4-GA-IL). The ultrasmall/Co3O4-GA-IL consists of Co3O4 co-assembled with IL modified GO to generate the HPS which can facilitate ion transfer channels through reduction of the electron and ion transportation path and transmission impedance. In addition, N-doping graphene can enhance the inherent electrical conductivity of Co3O4, which is proved by the DFT calculations. By virtue of the novel superstructure, the ultrasmall/Co3O4-GA-IL electrode demonstrates a high reversible capacity of 1,304 mAh·g−1, an enhanced high-rate capability (715 mAh·g−1 at 5 C), and a capacity retention of 98.4% even after 500 cycles at 5 C rate, which corresponds to 0.0003% capacity loss per cycle. Pouch cells based on the cathode are further fabricated and demonstrate excellent mechanical and electrochemical properties under bent and folded state, highlighting the practical application of our deliberately designed electrode in wearable electronics.

Although lithium-sulfur batteries (LSBs) promise high theoretical energy density and potential cost effectiveness, their applications are severely impeded by the shuttling and sluggish redox kinetics of lithium polysulfides (LiPSs). In this context, a Co

Coherent beam combining technology applied to multiple vortex beams is a promising method to generate high-power vortex beams. We utilize the coherent combination of multiple Laguerre–Gaussian beams at the waist plane and propose theoretically a practical generation system for a high-power beam carrying orbital angular momentum by considering oblique incidence. The results demonstrate that the orbital angular momentum distribution of the combined field is similar to that of a single Laguerre–Gaussian beam within the Rayleigh length. Moreover, the combined field has relativistic intensity local spots that exhibit stable spatial propagation. The proposed system may potentially be applied to intense vortical fields, large scale nuclear fusion device, such as suppressing stimulated Raman scattering and filamentation when a laser beam propagates in plasma.

Two-dimensional layered materials commonly face hindered electron transfer and poor structure stability, thus limiting their application in high-rate and long-term sodium ion batteries. In the current study, we adopt finite element simulation to guide the rational design of nanostructures. By calculating the von Mises stress distribution of a series of carbon materials, we find that the hollow biconcave structure could effectively alleviate the stress concentration resulting from expansion. Accordingly, we propose a biconcave-alleviated strategy based on the Aspergillus niger-derived carbon (ANDC) to construct ANDC/MoS2 with a hollow biconcave structure. The ANDC/MoS2 is endowed with an excellent long-term cyclability as an anode of sodium ion batteries, delivering a discharge capacity of 496 mAh g-1 after 1000 cycles at 1 A g-1. A capacity retention rate of 94.5% is achieved, an increase of almost seven times compared with the bare MoS2 nanosheets. Even at a high current density of 5 A g-1, a reversible discharge capacity around 400 mAh g-1 is maintained after 300 cycles. ANDC/MoS2 could also be used for efficient lithium storage. By using in situ TEM, we further reveal that the hollow biconcave structure of ANDC/MoS2 has enabled stable and fast sodiation/desodiation.

Identifying signals that govern the differentiation of tumor-infiltrating CD8

A strategy to develop a multifunctional sodium alginate personalized scaffold with enhanced mechanical stability, osteogenesis activity and excellent anti-inflammatory activity by cryogenic 3 D printing combined with subsequent crosslinking with Sr

In the ethylene signalling pathway, EIN2 is an essential signal transducer linking ethylene perception on endoplasmic reticulum to transcriptional regulation in the nucleus, EIN3/EIL1 transcription...

Background The extent and depth of facial nonmelanoma skin cancers and the involvement of adjacent structures are critical features for surgical planning, but they are difficult to assess clinically. High-resolution MRI (HR-MRI) with microscopy coil may facilitate detailed evaluation of skin lesions. The authors performed this prospective study to determine the value of high-resolution microscopy coil MRI in the preoperative evaluation of nonmelanoma skin cancer. Materials and methods Between October 2018 and August 2019, 16 lesions from fifteen consecutive patients with facial nonmelanoma skin cancer were evaluated using high-resolution microscopy coil MRI about tumor extent, depth, margins, characteristic, and their spatial relationship with adjacent structures. The preoperative HR-MRI results were compared with the intraoperative findings and with the histopathology, with special note to the depth of invasion. Results Among the 16 lesions, HR-MRI imaging was found to provide accurate evaluation of tumor extent, depth, and margins and determine whether there was involvement of adjacent structures. The tumor depth measured on HR-MRI showed good correlation with histopathologic results (CCC: 0.973), and Bland-Altman analysis finding no significant bias existed between the two measurements. All lesions except one were completely resected with primary excision. Only one lesion required further excision. During follow-up for 3-15 months, no tumor recurrence was observed in any case. Conclusions HR-MRI is an accurate, noninvasive imaging technique that can be used as preoperative evaluation tool for facial nonmelanoma skin cancer. It can accurate predict tumor depth, margins, and involvement of structure. The valuable information it provided facilitates surgeons optimize surgical planning.

Neutralizing antibody is an important indicator of vaccine efficacy, of which IgG is the main component. IgG can be divided into four subclasses. Up to now, studies analysing the humoral response to SARS-CoV-2 vaccination have mostly focused on measuring total IgG, and the contribution of specific IgG subclasses remains elusive. The aim of this study is to investigate the kinetics of neutralizing antibodies and IgG subclasses, and to explore their relationships in people vaccinated with inactivated COVID-19 vaccine. We conducted a prospective cohort study in 174 healthy adults aged 18-59 years old who were administrated 2 doses of CoronaVac 14 days apart and a booster dose 1 year after the primary immunization, and followed up for 15 months. Blood samples were collected at various time points after primary and booster immunization. We used live SARS-CoV-2 virus neutralizing assay to determine neutralizing ability against the wild-type strain and 4 variants (Beta, Gamma, Delta and Omicron) and ELISA to quantify SARS-CoV-2 RBD-specific IgG subclasses. The results showed that the 2-dose primary immunization only achieved low neutralizing ability, while a booster shot can significantly enhance neutralizing ability against the wild-type strain, Beta, Gamma, Delta and Omicron variants. IgG1 and IgG3 were the most abundant serum antibodies, and IgG2 and IgG4 were hardly detected at any time. The ratio of IgG1/IgG3 was positively associated with the neutralization ability. The underlying mechanism requires further exploration.

This paper considers a scenario in which the Terahertz (THz) transmitter equipped with a linear antenna array wishes to focus its beam to a desired spatial region in the array near-field. The goal is to compute the achievable spatial region and determine how the system parameters such as the carrier frequency, the array dimension and the user's location affect its beam focusing performance. First, based on a theorem from analytic geometry, we show that the achievable focusing spatial region constitutes a rotated ellipse, with the x and y coordinates denoting the range and angle, respectively. In this way, the determination of the spatial region is reduced to a problem of deriving the coverage of an ellipse. The achievable coverage is then obtained in closed form, and the construction of carrier frequency offsets that can analytically control the beam focusing performance is provided. Numerical results validate the theoretical findings and demonstrate the performance of the proposed method., Comment: 14 pages,3 figures

Abscisic acid (ABA) is a phytohormone essential for plants to respond to various environmental stresses, and abscisic acid-insensitive 5 (ABI5) is a basic leucine zipper transcription factor of the ABA signaling pathway. Exogenous ABA induces cold tolerance in bananas; however, the role of MaABI5-like in ABA-induced cold tolerance remains unexplored. The present study found that exogenous ABA alleviated chilling injury of ‘Fenjiao’ banana, induced the accumulation of endogenous ABA, unsaturated fatty acids, and flavonoid content, and reduced the saturated fatty acid content. Moreover, ABA treatment upregulated the transcription levels of MaABI5-like, fatty acid desaturation genes, and flavonoid synthesis-related genes during cold storage. More interestingly, MaABI5-like directly interacted with the promoter of genes related to fatty acid desaturation (MaFAD3-1, MaFAD3-4, MaFAD3-5, MaFAD6-2, MaFAD6-3) and flavonoid synthesis (MaPAL-like, MaPAL-like1, MaC4H-like3, Ma4CL-like1, Ma4CL-like10, MaCHS6-4-like, and MaFLS) and activated their expressions. Furthermore, the transient overexpression of MaABI5-like in ‘Fenjiao’ banana fruit and ectopic expression in tomato plants enhanced cold tolerance and upregulated fatty acid desaturation and flavonoid synthesis-related gene transcript levels. The reduced expression of MaABI5-like by virus-induced gene silencing in ‘Fenjiao’ banana increased chilling injury and downregulated the expression of fatty acid desaturation and flavonoid synthesis-related genes. Thus, the study indicates that MaABI5-like regulates ABA-induced cold tolerance by increasing unsaturated fatty acid and flavonoid content.

Objectives To determine the status of immune responses after primary and booster immunization for coronavirus disease 2019 (COVID-19) variants and evaluate the differences in disease-resistance based upon titers of neutralizing antibodies (NAbs) against the variants. Methods Participants aged 18 – 59 y received two doses of inactivated COVID-19 vaccine, 14 days apart, and a booster dose after 12 m. Blood samples were collected before vaccination (baseline), 1 and 6 m after primary immunization, and at multiple instances within 21 d of booster dose. NAbs against the spike protein of Wuhan-Hu-1 and three variants were measured using pseudovirus neutralization assays. Results Out of 400 enrolled participants, 387 completed visits scheduled within 6 m of the second dose, and 346 participated received the booster dose in the follow-up research. After 1 m of primary immunization, geometric mean titers (GMTs) of NAbs peaked for Wuhan-Hu-1, while GMTs of other variants were < 30. After 6 m of primary immunization, GMTs of NAbs against all strains were < 30. After 3 d of booster immunization, GMTs were unaltered, seroconversion rates reached approximately 50% after 7 d, and GMTs of NAbs against all strains peaked at 14 d. Conclusion Two-dose of inactivated COVID-19 vaccine induced the formation of NAbs and memory-associated immune responses, and high titers of NAbs against the variants obtained after booster immunization may further improve the effectiveness of the vaccine.

Guava fruit has a short postharvest shelf life at room temperature. Melatonin is widely used for preservation of various postharvest fruit and vegetables. In this study, an optimal melatonin treatment (600 μmol·L

Background The alcohol consumption pattern, alcoholic liver disease (ALD) prevalence and related risk factors among alcohol drinkers in Beijing haven’t been fully elucidated. Hence, a cross-sectional study was conducted to investigate potential link among these factors. Methods A two-stage stratified cluster sampling was carried out in Beijing. All participants were 25 years of age or older, possessed with medical insurance, and lived in Beijing for over 6 months. As part for this investigation, participants were asked to answer a questionnaire and undergo physical examination. The questionnaire included demographic information, alcohol intake, and medical history. The physical examination included physical and Fibrotouch tests. Moreover, 10 ml blood sample was collected from each subject to examine liver functions, perform routine blood, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV). Results Overall, 74,988 residents participated in our study. The proportion of current drinkers among all participants was 46.10%. The differences in gender, region, age group, education, annual household income, and occupation among lifetime abstainers, former drinkers, non-weekly and weekly drinkers were significantly different (PPP Conclusion Compared with other cities or regions in China, the level of alcohol consumption in Beijing is at an upper middle level. But the ALD prevalence is low likely because ethanol intake is relatively low. Our analysis revealed that heavy drinking is a major risk factor for ALD development. Hence, if alcohol consumption is unavoidable, we caution against heavy drinking.

Two-dimensional layered materials commonly face hindered electron transfer and poor structure stability, thus limiting their application in high-rate and long-term sodium ion batteries. In the current study, we adopt finite element simulation to guide the rational design of nanostructures. By calculating the von Mises stress distribution of a series of carbon materials, we find that the hollow biconcave structure could effectively alleviate the stress concentration resulting from expansion. Accordingly, we propose a biconcave-alleviated strategy based on the

As an inhibitor of ethylene receptors, 1-methylcyclopropene (1-MCP) can delay the ripening of papaya. However, improper 1-MCP treatment will cause a rubbery texture in papaya. Understanding of the underlying mechanism is still lacking. In the present work, a comparative sRNA analysis was conducted after different 1-MCP treatments and identified a total of 213 miRNAs, of which 44 were known miRNAs and 169 were novel miRNAs in papaya. Comprehensive functional enrichment analysis indicated that plant hormone signal pathways play an important role in fruit ripening. Through the comparative analysis of sRNAs and transcriptome sequencing, a total of 11 miRNAs and 12 target genes were associated with the ethylene and auxin signaling pathways. A total of 1741 target genes of miRNAs were identified by degradome sequencing, and nine miRNAs and eight miRNAs were differentially expressed under the ethylene and auxin signaling pathways, respectively. The network regulation diagram of miRNAs and target genes during fruit ripening was drawn. The expression of 11 miRNAs and 12 target genes was verified by RT-qPCR. The target gene verification showed that cpa-miR390a and cpa-miR396 target CpARF19-like and CpERF RAP2-12-like, respectively, affecting the ethylene and auxin signaling pathways and, therefore, papaya ripening.

Brassinosteroids act by delaying fruit ripening. The effects of different concentrations of 2,4-epibrassinolide (eBL) treatments on carambola fruit ripening were investigated. The results show that treatment of 2.8 mg L–1, eBL with 10 min effectively delays ripening and maintains the quality of carambola fruit. This is achieved by retarding color changes and firmness losses while maintaining high level of soluble protein content and vitamin C, and low organic acid content. eBL-delayed senescence may be due to the inhibition of respiration rate and enhanced antioxidant system. It is noteworthy that eBL treatment markedly reduces the content of fructose-6-phosphate (6-P-F) and enhances the activity of cytochrome oxidase (CCO), and the total activity of glucose-6-phosphate dehydrogenase (G-6-PDH) and 6-phosphate gluconate dehydrogenase (6-PGDH). eBL treatment induces the IAA and GA contents but reduces that of ABA. In general, senescence retardation and quality improvement by eBL treatment may be due to the enhanced antioxidant capacity and altered respiratory pathways.

Three-dimensional N/S co-doped succulent-like hierarchical carbon (3D NS-SHC) is synthesized by carbonization of a supramolecular cluster. In this supramolecular process, potassium citrate can act as a reliable carbon source, while the thiourea as a N/S source and then, two molecules gradually tend to generate a giant “all-in-one” precursor via hydrogen bonding verified by Independent Gradient Model (IGM) calculation. TEM and SEM images show the N/S co-doped carbon holds a novel 3D succulent-like hierarchical structure. For NS-SHC-8:8 sample, element mapping images display the uniform N/S atoms distribution. These distinct features can be related to the supramolecular polymerization which promotes in-situ N/S co-doping homogenously and conduces to build 3D structure. Typically, NS-SHC-8:8 electrode exhibits prominent specific capacitance (258.5 F g−1 at 0.5 A g−1) and excellent cycle stability (94.4% after 20000 cycles) in three-electrode system. Furthermore, an assembled quasi-solid state symmetric supercapacitor delivers good energy density (10.2 Wh kg−1 at 250 W kg−1) and steady cycle endurance (85.1% after 10000 cycles). These eximious behaviors of NS-SHC-8:8 are mainly attributed to (1) the uniform N/S atoms distribution and their synergistic effect, which brings extra Faradaic reaction to higher specific capacitance, (2) the charming 3D succulent-like hierarchical structure, which serves as a multifunctional reservoir that can accommodate the ion/charge and facilitate their migration to further promote the electrochemical performance. Above mentions suggest that this uniformly heteroatom-modified carbon material produced by supramolecular technique is promising for high-performance energy storage devices.

Bromodomain-containing proteins are known readers of histone acetylation that regulate chromatin structure and transcription. Although the functions of bromodomain-containing proteins in development, homeostasis, and disease states have been well studied, their role in self-renewal of hematopoietic stem and progenitor cells (HSPCs) remains poorly understood. Here, we performed a chemical screen using nine bromodomain inhibitors and found that the bromodomain and PHD finger-containing protein 1 (Brpf1) inhibitor OF-1 enhanced the expansion of Lin−Sca-1+c-Kit+ HSPCs ex vivo without skewing their lineage differentiation potential. Importantly, our results also revealed distinct functions of Brpf1 isoforms in HSPCs. Brpf1b promoted the expansion of HSPCs. By contrast, Brpf1a is the most abundant isoform in adult HSPCs but enhanced HSPC quiescence and decreased the HSPC expansion. Furthermore, inhibition of Brpf1a by OF-1 promoted histone acetylation and chromatin accessibility leading to increased expression of self-renewal-related genes (e.g. Mn1). The phenotypes produced by OF-1 treatment can be rescued by suppression of Mn1 in HSPCs. Our findings demonstrate that this novel bromodomain inhibitor OF-1 can promote the clinical application of HSPCs in transplantation.

Calcium ions (Ca2+) is an important element for plant cells and serve as second messengers, playing an important role in the regulation of plant physiology, specifically in postharvest fruits and vegetables. The roles of calcium and calcium-sensing receptors have been exhaustively studied in plants, and some of these receptors have been found to play a role in fruit ripening as well. However, a comprehensive overview of the manner in which calcium participates in regulating fruit development, ripening and the molecular mechanisms underlying fruit physiology and ripening have not been conducted. In this study, we reviewed the comprehensive roles of calcium in fruit development and ripening, attempting to elucidate the possible physiological and molecular mechanisms in fruit ripening. The roles of calcium sensors, including calmodulin (CaM), calmodulin-like (CML) proteins, calcineurin B-like proteins (CBL), and calcium-dependent protein kinases (CDPK), are discussed in fruit development and ripening. The interaction between the calcium signal and phytohormone signal pathways in fruit development and fruit ripening was also reviewed. The integral associations among calcium, calcium sensors, and fruit ripening were highlighted. This study provides a comprehensive overview of calcium signals in fruit development and ripening and may contribute to possible areas of interest for future research.