Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.

Horizontally Transferred Salivary Protein Promotes Insect Feeding by Suppressing Ferredoxin-Mediated Plant Defenses.

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.

Discovery of novel co-degradation CK1α and CDK7/9 PROTACs with p53 activation for treating acute myeloid leukemia.

Reactivating p53 activity to restore its anticancer function is an attractive cancer treatment strategy. In this study, we designed and synthesized a series of novel PROTACs to reactivate p53 via the co-degradation of CK1α and CDK7/9 proteins. Bioactivity studies showed that the selected PROTAC 13i exhibited potency antiproliferative activity in MV4-11 (IC50 = 0.096 ± 0.012 µM) and MOLM-13 (IC50 = 0.072 ± 0.014 µM) cells, and induced apoptosis of MV4-11 cells. Western-blot analysis showed that PROTAC 13i triple CK1α and CDK7/9 protein degradation resulted in the significantly increased expression of p53. At the same time, the transcriptional repression due to the degradation significantly reduced downstream gene expression of MYC, MDM2, BCL-2 and MCL-1, and reduced the inflammatory cytokine levels of TNF-α, IL-1ß and IL-6 in PMBCs. These results indicate the beneficial impact of simultaneous CK1α and CDK7/9 degradation for acute myeloid leukemia therapy.

Study on the Impact of Standardized Nursing During the Perioperative Period of Microballoon Compression in Patients with Trigeminal Neuralgia.

Background: Trigeminal neuralgia (TN), characterized by severe facial pain, warrants effective perioperative care. There is a critical need for evidence-based perioperative nursing interventions to enhance outcomes and well-being in patients undergoing microballoon compression for trigeminal neuralgia. Objective: This study aims to investigate the impact of standardized nursing during the perioperative period of microballoon compression in patients with trigeminal neuralgia (TN). Methods: A total of 22 TN patients admitted to our hospital from December 2021 to December 2022 underwent microballoon compression treatment. The control group (CG) received standard neurosurgical routine nursing, while the observation group (OG) received standardized nursing during the perioperative period. Comparative analysis included assessments of pain intensity, psychological status, sleep quality, overall quality of life, incidence of complications, and patient satisfaction. Results: Following nursing interventions, both groups exhibited a decrease in scores on the Neuropathic Pain Scale (NPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), and Pittsburgh Sleep Quality Index (PSQI). The OG demonstrated significantly lower scores compared to the CG (P < .05). Post-nursing, SF-36 scores decreased in both groups, with the OG displaying lower scores than the CG (P < .05). Although complications were less frequent in the OG, and patient satisfaction was higher, these differences were not statistically significant (P > .05). Conclusions: The implementation of standardized nursing during the perioperative period of microballoon compression in TN patients resulted in reduced pain intensity, improved psychological well-being, enhanced sleep quality, and better overall quality of life. These findings suggest the intervention's potential for valuable clinical application and merit further promotion.

Enhancing Fat Transplantation Efficiency in a Mouse Model through Pretreatment of Adipose-Derived Stem Cells with RIP3 Inhibitors.

BACKGROUND: Autologous fat transplantation, widely used in cosmetic and reparative surgery for volumetric enhancements, faces challenges with its inconsistent long-term survival rates. The technique's efficacy, crucial for its development, is hindered by unpredictable outcomes. Enriching fat grafts with adipose-derived stem cells (ADSCs) shows promise in improving survival efficiency. OBJECTIVES: This study aimed to explore the potential of receptor-interacting protein kinase 3 (RIP3) kinase inhibitors as a pretreatment for ADSCs in enhancing autologous fat graft retention over a long term. METHODS: ADSCs were isolated, cultured under normal or oxygen-glucose deprivation conditions, and mixed with particulate fat grafts to form distinct experimental groups in female nude mice. Fat graft mass and volume, along with underlying mechanisms, were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western blot analysis. RESULTS: The experimental group, pretreated with RIP3 kinase inhibitors, had higher graft mass and volume, greater adipocyte integrity, and increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels than control groups. Furthermore, the experimental group demonstrated lower expression of necroptosis pathway proteins in the short term and an ameliorated inflammatory response as indicated by interleukin-1 beta (IL-1ß), interleukin-10 (IL-10) mRNA levels, and histological analyses. Notably, enhanced neovascularization was evident in the experimental group. CONCLUSIONS: These findings suggest that RIP3 kinase inhibitor pretreatment of ADSCs can improve fat graft survival, promote adipocyte integrity, potentially decrease inflammation, and enhance neovascularization. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Multimodal Engineering of Catalytic Interfaces Confers Multi-Site Metal-Organic Framework for Internal Preconcentration and Accelerating Redox Kinetics in Lithium-Sulfur Batteries.

The development of highly efficient catalysts to address the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) in lithium-sulfur batteries (LSBs) remains a formidable challenge. In this study, a series of multi-site catalytic metal-organic frameworks (MSC-MOFs) were elaborated through multimodal molecular engineering to regulate both the reactant diffusion and catalysis processes. MSC-MOFs were crafted with nanocages featuring collaborative specific adsorption/catalytic interfaces formed by exposed mixed-valence metal sites and surrounding adsorption sites. This design facilitates internal preconcentration, a coadsorption mechanism, and continuous efficient catalytic conversion toward polysulfides concurrently. Leveraging these attributes, LSBs with an MSC-MOF-Ti catalytic interlayer demonstrated a 62 % improvement in discharge capacity and cycling stability. This resulted in achieving a high areal capacity (11.57 mAh cm-2 ) at a high sulfur loading (9.32 mg cm-2 ) under lean electrolyte conditions, along with a pouch cell exhibiting an ultra-high gravimetric energy density of 350.8 Wh kg-1 . Lastly, this work introduces a universal strategy for the development of a new class of efficient catalytic MOFs, promoting SRR and suppressing the shuttle effect at the molecular level. The findings shed light on the design of advanced porous catalytic materials for application in high-energy LSBs.

Metabolomics and machine learning approaches for diagnostic and prognostic biomarkers screening in sepsis.

BACKGROUND: Sepsis is a life-threatening disease with a poor prognosis, and metabolic disorders play a crucial role in its development. This study aims to identify key metabolites that may be associated with the accurate diagnosis and prognosis of sepsis. METHODS: Septic patients and healthy individuals were enrolled to investigate metabolic changes using non-targeted liquid chromatography-high-resolution mass spectrometry metabolomics. Machine learning algorithms were subsequently employed to identify key differentially expressed metabolites (DEMs). Prognostic-related DEMs were then identified using univariate and multivariate Cox regression analyses. The septic rat model was established to verify the effect of phenylalanine metabolism-related gene MAOA on survival and mean arterial pressure after sepsis. RESULTS: A total of 532 DEMs were identified between healthy control and septic patients using metabolomics. The main pathways affected by these DEMs were amino acid biosynthesis, phenylalanine metabolism, tyrosine metabolism, glycine, serine and threonine metabolism, and arginine and proline metabolism. To identify sepsis diagnosis-related biomarkers, support vector machine (SVM) and random forest (RF) algorithms were employed, leading to the identification of four biomarkers. Additionally, analysis of transcriptome data from sepsis patients in the GEO database revealed a significant up-regulation of the phenylalanine metabolism-related gene MAOA in sepsis. Further investigation showed that inhibition of MAOA using the inhibitor RS-8359 reduced phenylalanine levels and improved mean arterial pressure and survival rate in septic rats. Finally, using univariate and multivariate cox regression analysis, six DEMs were identified as prognostic markers for sepsis. CONCLUSIONS: This study employed metabolomics and machine learning algorithms to identify differential metabolites that are associated with the diagnosis and prognosis of sepsis patients. Unraveling the relationship between metabolic characteristics and sepsis provides new insights into the underlying biological mechanisms, which could potentially assist in the diagnosis and treatment of sepsis. TRIAL REGISTRATION: This human study was approved by the Ethics Committee of the Research Institute of Surgery (2021-179) and was registered by the Chinese Clinical Trial Registry (Date: 09/12/2021, ChiCTR2200055772).

The Effect of Various Temperatures on the Inflammatory Profile of Fat Graft Storage: An Experimental Study.

Fat tissue has been widely used as a filler material during plastic surgery, but unpredictable fat retention remains a significant concern. Fat tissue is vulnerable to ischemia and hypoxia, but it always has waiting time before injection in the operation theater. Apart from transferring fat tissue as quickly as possible after harvesting, washing the aspirate with cool normal saline is often used. However, the mechanisms of cool temperature acting on adipose tissue have yet to be fully elucidated. Herein, this study aims to explore the effect of preservation at different temperatures on the inflammatory profile of adipose tissue. Inguinal adipose tissue of rats was collected and cultured in vitro under 4°C, 10°C, and room temperature for 2 hours. The proportion of damaged adipocytes and an array of cytokines were determined. We observed that the damage rate of the adipocyte membrane was slightly higher at room temperature, but there was no significant difference, while we noticed increased IL-6 and MCP-1 levels in adipose tissue at room temperature ( P ＜0.01). The 4°C and 10°C cool temperatures may offer protection against proinflammatory states during the adipose tissue preserved in vitro.

Effects of G-CSF on hPDLSC proliferation and osteogenic differentiation in the LPS-induced inflammatory microenvironment.

BACKGROUND: Periodontitis is a chronic infectious disease of periodontal support tissue caused by microorganisms in dental plaque, which causes alveolar bone resorption and tooth loss. Periodontitis treatment goals include prevention of alveolar bone resorption and promotion of periodontal regeneration. We previously found that granulocyte colony-stimulating factor (G-CSF) was involved in periodontitis-related alveolar bone resorption through induction of an immune response and subsequent destruction of periodontal tissue. However, the mechanisms underlying the effects of G-CSF on abnormal bone remodeling have not yet been fully elucidated. Human periodontal ligament stem cells (hPDLSCs) are major modulators of osteogenic differentiation in periodontal tissues. Thus, the aim of this study was to investigated whether G-CSF acts effects on hPDLSC proliferation and osteogenic differentiation, as well as periodontal tissue repair. METHODS: hPDLSCs were cultured and identified by short tandem repeat analysis. The expression patterns and locations of G-CSF receptor (G-CSFR) on hPDLSCs were detected by immunofluorescence analysis. The effects of G-CSF on hPDLSCs in a lipopolysaccharide (LPS)-induced inflammatory microenvironment were investigated. Specifically, Cell-Counting Kit 8 (CCK8) and Alizarin red staining were used to examine hPDLSC proliferation and osteogenic differentiation; reverse transcription-polymerase chain reaction was performed to detect the expression patterns of osteogenesis-related genes (alkaline phosphatase [ALP], runt-related transcription factor 2 [Runx2], and osteocalcin [OCN]) in hPDLSCs; and Western blotting was used to detect the expression patterns of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) of PI3K/Akt signaling pathway. RESULTS: hPDLSCs exhibited a typical spindle-shaped morphology and good clonogenic ability. G-CSFR was mostly localized on the cell surface membrane. Analyses showed that G-CSF inhibited hPDLSC proliferation. Also, in the LPS-induced inflammatory microenvironment, G-CSF inhibited hPDLSC osteogenic differentiation and reduced the expression levels of osteogenesis-related genes. G-CSF increased the protein expression levels of hPDLSC pathway components p-PI3K and p-Akt. CONCLUSIONS: We found that G-CSFR was expressed on hPDLSCs. Furthermore, G-CSF inhibited hPDLSC osteogenic differentiation in vitro in the LPS-induced inflammatory microenvironment.

Effect of a neodymium-doped yttrium aluminium garnet laser on the physicochemical properties of contaminated titanium surfaces and macrophage polarization.

AIM(S): The objective of this study was to evaluate the changes in the physical and chemical properties of titanium surfaces contaminated by a Nd:YAG laser with different levels of energy and the regulation of macrophage polarization. MATERIALS AND METHODS: The titanium specimens were divided into four groups. The blank control group consisted of the above-mentioned contaminated titanium specimens, and the conditioned control group consisted of sandblasted and acid-etched (SLA) titanium surfaces. The blank control and condition control groups were sealed and preserved in a sterile dark box. There were two experimental groups treated with the Nd:YAG laser-one with 0.5 W and the second with 1.0 W. Surface characteristics were evaluated using scanning electron microscopy, surface profilometry, and contact angle assays. The macrophage viability and proliferation of mouse RAW246.7 were analysed, and the macrophage surface markers, macrophage cytokines, and inflammatory and anti-inflammatory genes were expressed. RESULTS: The Nd:YAG laser increased the hydrophilicity and roughness of the titanium surface after decontamination. Fewer RAW264.7 cells were observed on the titanium surface after Nd:YAG decontamination than on the contaminated titanium surface expressing the M1-type macrophage marker CCR7, whereas more cells were observed after decontamination than on the contaminated titanium surface expressing the M2-type macrophage marker CD206. Following Nd:YAG laser treatment, the secretion of the inflammatory cytokines IL-1ß and TNF-α by RAW264.7 cells on the titanium surface was decreased, whereas the secretion of the anti-inflammatory cytokines IL-4 and IL-10 was increased. RAW264.7 cells cultured for 3 days on the titanium surface after Nd:YAG decontamination treatment expressed significantly reduced levels of the inflammation-related genes IL-1ß, TNF-α, IL-6 and iNOS. The expression of the anti-inflammatory genes Arg-1, IL-4, IL-10 and TGF-ß by RAW264.7 cells was significantly up-regulated after 3 days of incubation on the titanium surface after Nd:YAG decontamination treatment. CONCLUSION(S): The Nd:YAG laser increased the hydrophilicity and roughness of the titanium surface after decontamination, and this change inhibited M1-type macrophage polarization and promoted M2-type macrophage polarization.

Design, synthesis, and biological evaluation of a novel series of 2-(2,6-dioxopiperidin-3-yl)isoquinoline-1,3(2H,4H)-dione derivatives as cereblon modulators.

In the current study, we designed and synthesised a novel series of 2-(2,6-dioxopiperidin-3-yl)isoquinoline-1,3(2H,4H)-dione derivatives as cereblon (CRBN) modulators. The results of the CCK8 assay revealed potent antiproliferative activity for the selected compound 10a against NCI-H929 (IC50=2.25 µM) and U239 (IC50=5.86 µM) cell lines. Compound 10a also can inhibit the TNF-α level (IC50=0.76 µM) in LPS stimulated PMBC and showed nearly no toxicity to this normal human cell line. The TR-FRET assay showed compound 10a having potent inhibitory activity against CRBN (IC50=4.83 µM), and the docking study confirmed a nice fitting of 10a into the active sites of CRBN. Further biology studies revealed compound 10a can increase the apoptotic events, arrest the NCI-H929 cells at G0/G1 cell cycle, and induce the ubiquitination degradation of IKZF1 and IKZF3 proteins by CRL4CRBN. These preliminary results suggested that compound 10a could serve as a potential antitumor drug and worthy of further investigation.

Comparison of Conduits Fabricated by Fresh and Predegenerated Skeletal Muscles for Peripheral Nerve Repairing.

ABSTRACT: Reconstruction of peripheral nerve injury remains a challenge for clinical medicine. Previous reports have confirmed that external oblique muscle-fabricated nerve conduit (EMC) could effectively be used to promote peripheral nerve regeneration. In this study, we compared between conduits fabricated from fresh muscle and conduits fabricated from predegenerated muscle for the repair of peripheral nerve defects in a mouse sciatic nerve transection model. We found that the number, diameter, and myelin sheath thickness of the myelinated nerve fibers of the regenerative nerve in the EMC group were larger than those of the predegenerated-EMC (P-EMC) group eight weeks after surgery. The sciatic function index and gastrocnemius wet-weight mass ratio in the EMC group were higher than those in the P-EMC group. The Bcl-2/Bax ratio and the number of Schwann cell nucleus in the proximal nerve stumps in the EMC group were greater than those in the P-EMC group. In conclusion, our results confirmed that the use of fresh skeletal muscle nerve conduit increased the Bcl-2/Bax ratio and promoted the survival of Schwann cells of the proximal nerve stump compared with that of predegenerated skeletal muscle nerve conduits, thus achieving better functional recovery after sciatic nerve defect.

Quercetin May Improve Fat Graft Survival by Promoting Fat Browning Peripherally.

BACKGROUND: Adipose browning occurs after white fat transfer. But its location and effects on fat graft survival remains controversial. This study was performed to locate the browning of fat grafts, and to explore the effects of quercetin on fat graft browning and fat graft survival. METHODS: Human fat granules were injected into the subcutaneous layer of 12 nude mice. Control group was injected with fat granules and 10% of normal saline, while quercetin group was injected with fat granules and 10% of quercetin. The graft samples (n = 6 for each group) were obtained in weeks 2, 4, 8 and 12. Weight retention rate of the grafts was calculated. Gene and protein expression of mitochondrial markers (silent information regulator 1, SIRT1; heat shock protein 60, HSP60), browning marker (uncoupling protein 1, UCP1), peroxisome proliferator-activated receptor-γ (PPAR-γ), vascular endothelial growth factor A (VEGF-A) were evaluated. Hematoxylin and eosin staining and anti-UCP1 staining were performed. RESULTS: Clusters of small multilocular beige adipocytes were observed in the periphery of fat grafts. Compared with control group, quercetin group had a higher weight retention rate, a higher gene/protein expression of SIRT1, HSP60, UCP1, PPAR-γ and VEGF-A, and a higher occurrence of peripheral adipose browning. CONCLUSIONS: Peripherally located adipose browning occurred after white fat transfer. It can be enhanced by the addition of quercetin through promoting mitochondrial function of fat cells, and may be one of the mechanisms that quercetin improves fat graft survival. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Role of Verteporfin in Prevention of Periprosthetic Capsular Fibrosis: An Experimental Study.

BACKGROUND: Capsular contracture (CC) characterized by excessive fibrosis is one of the most common complications after silicone implant surgery. Verteporfin (VP), an inhibitor of Yes-associated protein 1 (YAP1), has recently been found to reduce the fibrotic process. OBJECTIVES: The aim of this study was to use an in vivo rabbit model to evaluate the efficacy of VP for the prevention of CC. METHODS: Twenty-four New Zealand rabbits received 10-cc smooth saline silicone implants inserted in the dorsal skin and were randomly divided into 2 groups to receive 2 mL VP (1.5 mg/mL) or 2 mL phosphate-buffered saline solution instillation in the implant pocket. When the animals were killed on Day 60, capsule formation was observed both macroscopically and microscopically. Histologic evaluation included capsule thickness, fibrosis degree, and myofibroblast (α smooth muscle actin positive) content. In addition, the YAP1 expression level was examined by immunofluorescence staining. Transforming growth factor ß1, collagen I, and connective tissue growth factor expression were measured by real-time quantitative polymerase chain reaction. RESULTS: The VP-treated group exhibited thinner, more transparent capsules and less fibrosis than the control group at 60 days postsurgery (P < 0.05). Moreover, the VP treatment significantly reduced α smooth muscle actin, YAP1, transforming growth factor ß1, collagen I, and connective tissue growth factor expression levels in the capsular tissues (P < 0.05). CONCLUSIONS: VP reduced capsule formation after silicone implantation by inhibiting YAP1-mediated mechanical signaling, thereby attenuating excessive collagen deposition in the rabbit model. This preclinical study may provide a feasible strategy to prevent periprosthetic capsular fibrosis in clinical application.

Granulocyte colony-stimulating factor (G-CSF) mediates bone resorption in periodontitis.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is an important immune factor that mediates bone metabolism by regulating the functions of osteoclasts and osteoblasts. Bone loss is a serious and progressive result of periodontitis. However, the mechanisms underlying the effects of G-CSF on periodontal inflammation have yet not been completely elucidated. Here, we examined whether an anti-G-CSF antibody could inhibit bone resorption in a model of experimental periodontitis and investigated the local expression of G-CSF in periodontal tissues. METHODS: Experimental periodontitis was induced in mice using ligatures. The levels of G-CSF in serum and bone marrow were measured; immunofluorescence was then performed to analyze the localization and expression of G-CSF in periodontal tissues. Mice with periodontitis were administered anti-G-CSF antibody by tail vein injection to assess the inhibition of bone resorption. Three-dimensional reconstruction was performed to measure bone destruction-related parameters via micro-computed tomography analysis. Immunofluorescence staining was used to investigate the presence of osteocalcin-positive osteoblasts; tartrate-resistant acid phosphatase (TRAP) staining was used to observe osteoclast activity in alveolar bone. RESULTS: The level of G-CSF in serum was significantly elevated in mice with periodontitis. Immunofluorescence analyses showed that G-CSF was mostly expressed in the cell membrane of gingival epithelial cells; this expression was enhanced in the periodontitis group. Additionally, systemic administration of anti-G-CSF antibody significantly inhibited alveolar bone resorption, as evidenced by improvements in bone volume/total volume, bone surface area/bone volume, trabecular thickness, trabecular spacing, and trabecular pattern factor values. Immunofluorescence analysis revealed an enhanced number of osteocalcin-positive osteoblasts, while TRAP staining revealed reduction of osteoclast activity. CONCLUSIONS: G-CSF expression levels were significantly up-regulated in the serum and gingival epithelial cells. Together, anti-G-CSF antibody administration could alleviates alveolar bone resorption, suggesting that G-CSF may be one of the essential immune factors that mediate the bone loss in periodontitis.

Evolutionary history of the C-repeat binding factor/dehydration-responsive element-binding 1 (CBF/DREB1) protein family in 43 plant species and characterization of CBF/DREB1 proteins in Solanum tuberosum.

BACKGROUND: Plants are easily affected by temperature variations, and high temperature (heat stress) and low temperature (cold stress) will lead to poor plant development and reduce crop yields. Therefore, it is very important to identify resistance genes for improving the ability of plants to resist heat stress or cold stress by using modern biotechnology. Members of the C-repeat binding factor/Dehydration responsive element-binding 1 (CBF/DREB1) protein family are related to the stress resistance of many plant species. These proteins affect the growth and development of plants and play vital roles during environmental stress (cold, heat, drought, salt, etc.). In this study, we identified CBF/DREB1 genes from 43 plant species (including algae, moss, ferns, gymnosperms, angiosperms) by using bioinformatic methods to clarify the characteristics of the CBF/DREB1 protein family members and their functions in potato under heat and cold stresses. RESULTS: In this study, we identified 292 CBF/DREB1 proteins from 43 plant species. However, no CBF/DREB1 protein was found in algae, moss, ferns, or gymnosperms; members of this protein family exist only in angiosperms. Phylogenetic analysis of all the CBF/DREB1 proteins revealed five independent groups. Among them, the genes of group I do not exist in eudicots and are found only in monocots, indicating that these genes have a special effect on monocots. The analysis of motifs, gene duplication events, and the expression data from the PGSC website revealed the gene structures, evolutionary relationships, and expression patterns of the CBF/DREB1 proteins. In addition, analysis of the transcript levels of the 8 CBF/DREB1 genes in potato (Solanum tuberosum) under low-temperature and high-temperature stresses showed that these genes were related to temperature stresses. In particular, the expression levels of StCBF3 and StCBF4 in the leaves, stems, and roots significantly increased under high-temperature conditions, which suggested that StCBF3 and StCBF4 may be closely related to heat tolerance in potato. CONCLUSION: Overall, members of the CBF/DREB1 protein family exist only in angiosperms and plays an important role in the growth and development of plants. In addition, the CBF/DREB1 protein family is related to the heat and cold resistance of potato. Our research revealed the evolution of the CBF/DREB1 family, and is useful for studying the precise functions of the CBF/DREB1 proteins when the plants are developing and are under temperature stress.

Protein targeting chimeric molecules specific for dual bromodomain 4 (BRD4) and Polo-like kinase 1 (PLK1) proteins in acute myeloid leukemia cells.

Proteolysis targeting chimeras (PROTACs) are hetero-bifunctional molecules that could simultaneously bind to the target protein and the E3 ubiquitin ligase, thereby leading to selective degradation of the target protein. Polo-like kinase 1 (PLK1) and bromodomain 4 (BRD4) are both attractive therapeutic targets in acute myeloid leukemia (AML). Here, we developed a small-molecule BRD4 and PLK1 degrader HBL-4 based on PROTAC technology, which leads to fast, efficient, and prolonged degradation of BRD4 and PLK1 in MV4-11 cells tested in vitro and vivo, and potent anti-proliferation and BRD4 and PLK1 degradation ability in human acute leukemia MOLM-13 and KG1 cells. Meanwhile, HBL-4 more effectively suppresses c-Myc levels than inhibitor BI2536, resulting in more effective inducing apoptosis activity in MV4-11 cells. At the same time, HBL-4 induced dramatically improved efficacy in the MV4-11 tumor xenograft model as compared with BI2536. This study is, to our knowledge, the first reports about dual PLK1 and BRD4 degraders, which potentially represents an important therapeutic advance in the treatment of cancer.

Platelet-Rich Fibrin Improves Fat Graft Survival Possibly by Promoting Angiogenesis and Adipogenesis, Inhibiting Apoptosis, and Regulating Collagen Production.

BACKGROUND: Platelet-rich fibrin (PRF) can promote fat graft survival, but limited data are currently available, and the underlying mechanism of this effect has not yet been explained. OBJECTIVES: The aim of this study was to explore the mechanism by which PRF promotes fat graft survival, from the aspects of angiogenesis, adipogenesis, cellular apoptosis, and collagen production. METHODS: Nude mice were randomly assigned to a PRF group (subcutaneously injected with PRF and fat in the ratio of 1:5 by volume) and a control group (subcutaneously injected with normal saline and fat in the ratio of 1:5 by volume). On days 0, 3, 7, 14, 21, and 28 after transplantation, graft samples (n = 12) were obtained for quantification of target growth factors. In weeks 1, 2, 3, and 4 after transplantation, graft samples (n = 12) were obtained for the following evaluations. The volume and weight retention rates were calculated; gene and protein expression of vascular endothelial growth factor A (VEGF-A), peroxisome proliferator-activated receptor γ (PPAR-γ), COL1-A1, and BAX were evaluated; hematoxylin & eosin staining, Masson's trichrome staining, α smooth muscle actin staining, and perilipin-1 staining were performed to evaluate graft survival. RESULTS: After transplantation, the concentrations of growth factors produced by the fat increased to varying degrees, and the addition of PRF made these concentration changes ever greater. Compared with the control group, the PRF group had a higher volume and weight retention rate, a higher expression level of VEGF-A and PPAR-γ, a lower expression level of COL1-A1 and BAX, a higher vessel density, less fibrosis, and more viable adipocytes. CONCLUSIONS: PRF can promote autocrine function of the grafted fat to produce more growth factors. It greatly increased fat retention rate, possibly by promoting vascularization and adipogenic differentiation, inhibiting cellular apoptosis, and regulating collagen production.

Deep Sequencing Reveals Early Reprogramming of Arabidopsis Root Transcriptomes Upon Ralstonia solanacearum Infection.

Bacterial wilt caused by the bacterial pathogen Ralstonia solanacearum is one of the most devastating crop diseases worldwide. The molecular mechanisms controlling the early stage of R. solanacearum colonization in the root remain unknown. Aiming to better understand the mechanism of the establishment of R. solanacearum infection in root, we established four stages in the early interaction of the pathogen with Arabidopsis roots and determined the transcriptional profiles of these stages of infection. A total 2,698 genes were identified as differentially expressed genes during the initial 96 h after infection, with the majority of changes in gene expression occurring after pathogen-triggered root-hair development observed. Further analysis of differentially expressed genes indicated sequential activation of multiple hormone signaling cascades, including abscisic acid (ABA), auxin, jasmonic acid, and ethylene. Simultaneous impairment of ABA receptor genes promoted plant wilting symptoms after R. solanacearum infection but did not affect primary root growth inhibition or root-hair and lateral root formation caused by R. solanacearum. This indicated that ABA signaling positively regulates root defense to R. solanacearum. Moreover, transcriptional changes of genes involved in primary root, lateral root, and root-hair formation exhibited high temporal dynamics upon infection. Taken together, our results suggest that successful infection of R. solanacearum on roots is a highly programmed process involving in hormone crosstalk.

Type III Secretion-Dependent and -Independent Phenotypes Caused by Ralstonia solanacearum in Arabidopsis Roots.

The causal agent of bacterial wilt, Ralstonia solanacearum, is a soilborne pathogen that invades plants through their roots, traversing many tissue layers until it reaches the xylem, where it multiplies and causes plant collapse. The effects of R. solanacearum infection are devastating, and no effective approach to fight the disease is so far available. The early steps of infection, essential for colonization, as well as the early plant defense responses remain mostly unknown. Here, we have set up a simple, in vitro Arabidopsis thaliana-R. solanacearum pathosystem that has allowed us to identify three clear root phenotypes specifically associated to the early stages of infection: root-growth inhibition, root-hair formation, and root-tip cell death. Using this method, we have been able to differentiate, on Arabidopsis plants, the phenotypes caused by mutants in the key bacterial virulence regulators hrpB and hrpG, which remained indistinguishable using the classical soil-drench inoculation pathogenicity assays. In addition, we have revealed the previously unknown involvement of auxins in the root rearrangements caused by R. solanacearum infection. Our system provides an easy-to-use, high-throughput tool to study R. solanacearum aggressiveness. Furthermore, the observed phenotypes may allow the identification of bacterial virulence determinants and could even be used to screen for novel forms of early plant resistance to bacterial wilt.