Proteomics and SSH Analyses of ALA-Promoted Fruit Coloration and Evidence for the Involvement of a MADS-Box Gene, MdMADS1

Skin color is a key quality attribute of fruits and how to improve fruit coloration has long been a major concern. 5-Aminolevulinic acid (ALA), a natural plant growth regulator, can significantly increase anthocyanin accumulation in fruit skin and therefore effectively improve coloration of many fruits, including apple. However, the molecular mechanism how ALA stimulates anthocyanin accumulation in fruit skin remains unknown. Here, we investigated the impact of ALA on apple skin at the protein and mRNA levels. A total of 85 differentially expressed proteins in apple skins between ALA and water treatment (control) were identified by complementary gel-based and gel-freeseparation techniques. Most of these differentially expressed proteins were up-regulated by ALA. Function analysis suggested that 87.06% of the ALA-responsive proteins were associated with fruit ripening. To further screen ALA-responsive regulators, we constructed a subtracted cDNA library (tester: ALA treatment; driver: control) and obtained 104 differentially expressed unigenes, of which 38 unigenes were indicators for the fruit ripening-related gene. The differentially changed proteins and transcripts did not correspond well at an individual level, but showed similar regulated direction in function at the pathway level. Among the identified fruit ripening-related genes, the expression of MdMADS1, a developmental transcription regulator of fruit ripening, was positively correlated with expression of anthocyanin biosynthetic genes (MdCHS, MdDFR, MdLDOX and MdUFGT) in apple skin under ALA treatment. Moreover, overexpression of MdMADS1 enhanced anthocyanin content in transformed apple calli, which was further enhanced by ALA. The anthocyanin content in MdMADS1-silenced calli was less than that in the control with ALA treatment, but higher than that without ALA treatment. These results indicated that MdMADS1 is involved in ALA-induced anthocyanin accumulation. In addition, anthocyanin-related verification in apple calli suggested that the regulation of MdMADS1 on anthocyanin biosynthesis was partially independent of fruit ripening process. Taken together, our findings provide insight into the mechanism how ALA regulates anthocyanin accumulation and add new information on transcriptase regulators of fruit coloration

Inserting Extra Train Services on High-Speed Railway

With the aim of supporting future traffic needs, an account of how to reconstruct an existing cyclic timetable by inserting additional train services will be given in this paper. The Timetable-based Extra Train Services Inserting (TETSI) problem is regarded as an integration of railway scheduling and rescheduling problem. The TETSI problem therefore is considered involving many constraints, such as flexible running times, dwell times, headway and time windows. Characterized based on an event-activity graph, a general Mixed Integer Program model for this problem is formulated. In addition, several extensions to the general model are further proposed. The real-world constraints that concerning the acceleration and deceleration times, priority for overtaking, allowed adjustments, periodic structure and frequency of services are incorporated into the general model. From numerical investigations using data from Shanghai-Hangzhou High-Speed Railway in China, the proposed framework and associated techniques are tested and shown to be effective

Research progress on applications and mechanisms of osteogenesis effect of magnetic fields in oral field

Magnetic fields are safe and used in noninvasive physical therapies. Numerous studies have confirmed that magnetic fields have good osteogenic effects and certain value for clinical application in accelerating orthodontic tooth movement, promoting bone-implant integration, promoting fracture healing and improving the effects of distraction osteogenesis. Magnetic fields are expected to become applied as effective auxiliary methods for treating oral diseases. To support the clinical application of magnetic fields, this article reviews the applications of magnetic fields in the oral cavity, the biological effects on bone cells and the molecular mechanisms through which magnetic fields regulate bone metabolism. The biological effects of magnetic fields on bone cells include promoting osteogenesis by osteoblasts and mesenchymal stem cells and inhibiting bone resorption by osteoclasts. At the molecular level, bone cells sense and respond to magnetic stimulation, and through various mechanisms, such as displacement currents, Lorentz forces, and free radical pair effects, stimuli are transformed into biologically recognizable electrical signals that activate complex downstream signaling pathways, such as the P2 purinergic receptor signaling pathway, adenosine receptor signaling pathway, transforming growth factor-β receptor signaling pathway, mammalian target of rapamycin (mTOR) pathway, and Notch pathway. In addition, magnetic parameters, which are the factors affecting the osteogenic effects of magnetic fields, are discussed. However, the mechanisms of the osteogenic effects of magnetic fields are unclear, and further studies of these mechanisms could provide effective strategies for bone regeneration and periodontal tissue regeneration. In addition, considering the target of magnetic field therapies, combination with other drugs could lead to new strategies for the treatment of oral diseases

Demographic strategies of a dominant tree species in response to logging in a degraded subtropical forest in Southeast China

International audienceAbstractKey messageThe demography of pioneer tree species (Pinus massonianaLamb.) is significantly affected by logging in Southeast China. Logging negatively affects the population growth rate ofP. massoniana, which facilitates the growth of individual trees but has no effect on reproduction probability. The survival and growth of seedlings contribute the most to population growth.ContextSubtropical forest degradation caused by unreasonable disturbances is closely related to anthropogenic activities in Southeast China, and the frequent small-scale logging activity by local people was the dominated disturbance regime in forests in this region over the past several decades.AimsThe objective of this study is to evaluate the demographic consequences of logging on Pinus massoniana, a pioneer tree species, at individual level (survival, growth, and fecundity) and population level (the population growth rate and size distribution) over short-term period.MethodsThe size of tree individuals was combined with vital rates using various modeling approaches based on demographic data from three annual censuses. The integral projection model (IPM) was constructed and used to conduct comparative demographic analyses.ResultsLogging negatively affected the population growth rate: from a slight expansion before logging to a moderate decline after logging. This study found a significant reduction in seedling recruitment after logging, and plant growth and mortality were slightly enhanced. The survival of seedlings greatly contributes to population growth rate compared to other life stages for both periods (before and after logging) while its relative importance decreases after logging. Seedling growth is also important to population growth, and its relative importance increased after logging. Shrinkage and fecundity have a minimal contribution effect on the population growth rate.ConclusionGrowing plants in a nursery with a similar demography to P. massoniana could be beneficial for pioneer species regeneration in that this will improve the survival rate and growth of small individuals after logging

Dihydro­allocryptopine

In the title compound [systematic name: 7,8-dimeth­oxy-11-methyl-17,19-dioxa-11-aza­tetra­cyclo­[12.7.0.04,9.016,20]henicosa-1(21),4,6,8,14,16 (20)-hexaen-2-ol], C21H25NO5, the benzene rings are inclined at a dihedral angle of 23.16 (5)°. One of the meth­oxy C atoms is close to coplanar with its attached ring [deviation = 0.129 (3) Å], whereas the other is orientated away from the ring [deviation = −1.124 (2) Å]. The 10-membered ring is highly puckered, and the OH and CH3 substituents project to the same side of the ring. In the crystal, O—H⋯O hydrogen bonds link the mol­ecules into [010] chains and C—H⋯O and C—H⋯π inter­actions consolidate the packing

Pleistocene glacial cycle effects on the phylogeography of the Chinese endemic bat species, Myotis davidii

<p>Abstract</p> <p>Background</p> <p>Global climatic oscillations, glaciation cycles and the unique geographic topology of China have profoundly influenced species population distributions. In most species, contemporary distributions of populations cannot be fully understood, except in a historical context. Complex patterns of Pleistocene glaciations, as well as other physiographic changes have influenced the distribution of bat species in China. Until this study, there had been no phylogeographical research on <it>Myotis davidii</it>, an endemic Chinese bat. We used a combination of nuclear and mitochondrial DNA markers to investigate genetic diversity, population structure, and the demographic history of <it>M. davidii</it>. In particular, we compared patterns of genetic variation to glacial oscillations, topography, and environmental variation during the Pleistocene in an effort to explain current distributions in light of these historical processes.</p> <p>Results</p> <p><it>M. davidii </it>comprises three lineages (MEP, SWP and SH) based on the results of molecular variance analysis (AMOVA) and phylogenetic analyses. The results of a STRUCTURE analysis reveal multi-hierarchical population structure in <it>M. davidii</it>. Nuclear and mitochondrial genetic markers reveal different levels of gene flow among populations. In the case of mtDNA, populations adhere to an isolation-by-distance model, whereas the individual assignment test reveals considerable gene flow between populations. MDIV analysis indicate that the split of the MEP and SWP/SH lineages, and from the SWP and SH lineages were at 201 ka BP and 158 ka BP, respectively. The results of a mismatch distribution analysis and neutrality tests indicate a population expansion event at 79.17 ka BP and 69.12 ka BP in MEP and SWP, respectively.</p> <p>Conclusions</p> <p>The complex demographic history, discontinuous extant distribution of haplotypes, and multiple-hierarchy population structure of <it>M. davidii </it>appear associated with climatic oscillations, topography and eco-environmental variation of China. Additionally, the three regions are genetically differentiated from one another in the entire sample set. The degree of genetic differentiation, based on the analysis of mtDNA and nDNA, suggests a male-mediated gene flow among populations. Refuges were in the MEP, SH and the lower elevations of SWP regions. This study also provides insights for conservation management units (MEP, SWP and SH).</p

Application of a modified U-shaped forearm flap for the repair of small and medium-sized defects in the oral and maxillary areas

Objective To evaluate the applicability of a modified U-shaped forearm flap for the repair of small- and medium-sized defects in the oral and maxillary areas to provide a reference for clinicians. Methods This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ten patients with small- and medium-sized defects in the oral and maxillary areas underwent surgical repair using modified U-shaped forearm flaps. There were 8 males and 2 females aged 43-72 years. The donor site was apposed primarily after harvesting the modified U-shaped forearm skin flap. The flaps ranged from 6 cm &#x00D7; 4 cm to 8 cm &#x00D7; 5 cm in size. Six months after the operation, hand movements (finger extension, fist clenching, wrist rotation upward and wrist rotation downward), the forearm donor site, hand sensations and the satisfaction score for the postoperative quality of the scar at the donor site were evaluated (0 to 10; 0: very unattractive, 10: very satisfactory). Results A total of 10 patients with modified U-shaped forearm flaps survived. One patient developed venous crisis 24 hours after surgery and survived after surgical exploration. Delayed healing occurred at the donor site of the forearm in 1 patient, and the wounds at the donor site of the forearm in the other patients all healed in the first stage. One patient presented with dysesthesia in the hand 2 weeks after surgery and recovered within 3 months. Six months after surgery, all patients had no limited hand movement and no paresthesia at the forearm donor site or hand. The patients were basically satisfied with the appearance of the donor site,and the average satisfaction score of the subjective questionnaire was 8.4 points. Conclusion Modified U-shaped forearm flaps can directly close forearm donor site wounds, which avoids surgical trauma to the secondary donor site and significantly reduces related complications. Modified U-shaped forearm flaps provide an alternative to conventional forearm flaps for the repair of small- and medium-sized defects in the oral and maxillary areas

Electroplating lithium transition metal oxides.

Materials synthesis often provides opportunities for innovation. We demonstrate a general low-temperature (260°C) molten salt electrodeposition approach to directly electroplate the important lithium-ion (Li-ion) battery cathode materials LiCoO2, LiMn2O4, and Al-doped LiCoO2. The crystallinities and electrochemical capacities of the electroplated oxides are comparable to those of the powders synthesized at much higher temperatures (700° to 1000°C). This new growth method significantly broadens the scope of battery form factors and functionalities, enabling a variety of highly desirable battery properties, including high energy, high power, and unprecedented electrode flexibility

Integration of multi-omics and clinical treatment data reveals bladder cancer therapeutic vulnerability gene combinations and prognostic risks

BackgroundBladder cancer (BCa) is a common malignancy of the urinary tract. Due to the high heterogeneity of BCa, patients have poor prognosis and treatment outcomes. Immunotherapy has changed the clinical treatment landscape for many advanced malignancies, opening new avenues for the precise treatment of malignancies. However, effective predictors and models to guide clinical treatment and predict immunotherapeutic outcomes are still lacking.MethodsWe downloaded BCa sample data from The Cancer Genome Atlas to identify anti-PD-L1 immunotherapy-related genes through an immunotherapy dataset and used machine learning algorithms to build a new PD-L1 multidimensional regulatory index (PMRI) based on these genes. PMRI-related column-line graphs were constructed to provide quantitative tools for clinical practice. We analyzed the clinical characteristics, tumor immune microenvironment, chemotherapy response, and immunotherapy response of patients based on PMRI system. Further, we performed function validation of classical PMRI genes and their correlation with PD-L1 in BCa cells and screening of potential small-molecule drugs targeting PMRI core target proteins through molecular docking.ResultsPMRI, which consists of four anti-PD-L1 immunotherapy-associated genes (IGF2BP3, P4HB, RAC3, and CLK2), is a reliable predictor of survival in patients with BCa and has been validated using multiple external datasets. We found higher levels of immune cell infiltration and better responses to immunotherapy and cisplatin chemotherapy in the high PMRI group than in the low PMRI group, which can also be used to predict immune efficacy in a variety of solid tumors other than BCa. Knockdown of IGF2BP3 inhibited BCa cell proliferation and migration, and IGF2BP3 was positively correlated with PD-L1 expression. We performed molecular docking prediction for each of the core proteins comprising PMRI and identified 16 small-molecule drugs with the highest affinity to the target proteins.ConclusionsOur PD-L1 multidimensional expression regulation model based on anti-PD-L1 immunotherapy-related genes can accurately assess the prognosis of patients with BCa and identify patient populations that will benefit from immunotherapy, providing a new tool for the clinical management of intermediate and advanced BCa

Internalized compartments encapsulated nanogels for targeted drug delivery

Drug delivery systems inspired by natural particulates hold great promise for targeted cancer therapy. Endosome formed by internalization of plasma membrane has massive of membrane proteins and receptors on the surface, which is able to specifically target to the homotypic cells. Herein, we describe a simple method to fabricate an endosome membrane-coated nanogel (EM-NG) from source cancer cells. Following intracellular uptake of methacrylated hyaluronic acid (m-HA) adsorbed SiO2/Fe3O4 nanoparticles encapsulating crosslinker and photoiniator, EM-NG was readily prepared through in situ crosslinking initiated under UV irradiation inside endosome. The resulting endosome mimetic nanogels loaded with Doxorubicin (DOX) displayed enhanced internalization efficiency to the source cells through a specific homotypic affinity in vitro. However, when treated the non-source cells, the EM-NGs exhibited insignificant difference in therapeutic efficiency compared to bare HA nanogel with DOX. This study illustrates the potential of utilizing endosome membrane-mimicking formulation for targeted cancer therapy, and offers guideline for developing natural particulates-inspired drug delivery system