Application of thermosensitive-hydrogel combined with dental pulp stem cells on the injured fallopian tube mucosa in an animal model

Objectives: Fallopian tube (FT) injury is an important factor that can lead to tubal infertility. Stem-cell-based therapy shows great potential for the treatment of injured fallopian tube. However, little research has shown that mesenchymal stem cells (MSCs) can be used to treat fallopian tube damage by in situ injection. In this study, we in situ transplanted PF127 hydrogel encapsulating dental pulp stem cells (DPSCs) into the injured sites to promote the repair and regeneration of fallopian tube injury.Materials and methods: The properties of dental pulp stem cells were evaluated by flow cytometry, immunofluorescence analysis, and multi-differentiation detection. The immunomodulatory and angiogenic characteristics of dental pulp stem cells were analyzed on the basis of the detection of inflammatory factor expression and the formation of capillary-like structures, respectively. The biocompatibility of PF127 hydrogel was evaluated by using Live/Dead and CCK-8 assays. The effects of PF127 hydrogel containing dental pulp stem cells on the repair and regeneration of fallopian tube injury were evaluated by histological analysis [e.g., hematoxylin and eosin (H&E) and Masson’s trichrome staining, TUNEL staining, immunofluorescence staining, and immunohistochemistry], Enzyme-linked immunosorbent assay (ELISA), and RT-PCR detections.Results: Dental pulp stem cells had MSC-like characteristics and great immunomodulatory and angiogenic properties. PF127 hydrogel had a thermosensitive feature and great cytocompatibility with dental pulp stem cells. In addition, our results indicated that PF127 hydrogel containing dental pulp stem cells could promote the repair and regeneration of fallopian tube damage by inhibiting cell apoptosis, stimulating the secretion of angiogenic factors, promoting cell proliferation, modulating the secretion of inflammatory factors, and restoring the secretion of epithelial cells.Conclusion: In this study, our results reported that in situ injection of PF127 hydrogel encapsulating dental pulp stem cells into the injured sites could provide an attractive strategy for the future treatment of fallopian tube injury in clinical settings

Newly Approved and Emerging Agents in HER2-Positive Metastatic Breast Cancer.

Human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) is an aggressive tumor type, accounting for 15% to 20% of the approximately 300,000 new BC cases in the United States each year. The goal of this review is to discuss the evolving landscape of therapies for HER2+ metastatic BC (mBC). Targeted therapies that have been the standard of care (SOC) for HER2+ mBC for almost a decade have greatly improved patient outcomes. The SOC for the first-line treatment of HER2+ mBC continues to be HER2-targeted monoclonal antibodies (mAbs) + a taxane, but recent updates in the second-line setting favor use of a newer HER2-targeted antibody-drug conjugate (ADC), trastuzumab deruxtecan, versus the prior SOC ADC, trastuzumab emtansine. Numerous options are now available in the third line and beyond, including tyrosine kinase inhibitor (TKI) regimens, newer mAbs, and other ADCs. The optimal course of treatment for individual patients can be guided by location of metastases, prior therapies, concomitant biomarkers, and monitoring and management of adverse events. Ongoing trials will further the evolution of the HER2+ mBC treatment landscape. Furthermore, next-generation ADCs, TKIs, and classes of drugs that have not been approved for the treatment of HER2+ mBC, including immune checkpoint inhibitors and cyclin-dependent kinase 4 and 6 inhibitors, are also being evaluated for their efficacy in the first and second line. Although the influx of new drugs may complicate treatment decisions for physicians, having a multitude of options will undoubtedly further improve patient outcomes and patient-centered care

Targeted Drugs as Maintenance Therapy after Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma

The treatment landscape for mantle cell lymphoma (MCL) is rapidly evolving toward the incorporation of novel and biologically targeted pharmaceuticals with improved disease activity and gentler toxicity profiles compared with conventional chemotherapeutics. Upfront intensive treatment of MCL includes autologous stem cell transplantation (SCT) consolidation aimed at deepening and lengthening disease remission, but subsequent relapse occurs. Maintenance therapy after autologous SCT in patients with MCL in remission features lower-intensity treatments given over extended periods to improve disease outcomes. Targeted drugs are a natural fit for this space, and are the focus of considerable clinical investigation. This review summarizes recent advances in the field and their potential impact on treatment practices for MCL

Uplink power allocation based on non-orthogonal multiple access system

In view of the non-orthogonal multiple access(NOMA) system uplink,an optimal power allocation scheme based on the Dinkelbach algorithm was proposed in order to solve the energy efficiency optimization problem under the premise of ensuring the minimum user rate requirement.Simulation results showed that when the maximum user transmit power limit was set as 15 dBm,the energy efficiency of system was improved by 38 bit·J-1·Hz-1

A Hybrid Parallel Balanced Phasmatodea Population Evolution Algorithm and Its Application in Workshop Material Scheduling

The phasmatodea population evolution algorithm (PPE) is a recently proposed meta-heuristic algorithm based on the evolutionary characteristics of the stick insect population. The algorithm simulates the features of convergent evolution, population competition, and population growth in the evolution process of the stick insect population in nature and realizes the above process through the population competition and growth model. Since the algorithm has a slow convergence speed and falls easily into local optimality, in this paper, it is mixed with the equilibrium optimization algorithm to make it easier to avoid the local optimum. Based on the hybrid algorithm, the population is grouped and processed in parallel to accelerate the algorithm’s convergence speed and achieve better convergence accuracy. On this basis, we propose the hybrid parallel balanced phasmatodea population evolution algorithm (HP_PPE), and this algorithm is compared and tested on the CEC2017, a novel benchmark function suite. The results show that the performance of HP_PPE is better than that of similar algorithms. Finally, this paper applies HP_PPE to solve the AGV workshop material scheduling problem. Experimental results show that HP_PPE can achieve better scheduling results than other algorithms

Exploiting Syntactic and Semantic Information for Textual Similarity Estimation

The textual similarity task, which measures the similarity between two text pieces, has recently received much attention in the natural language processing (NLP) domain. However, due to the vagueness and diversity of language expression, only considering semantic or syntactic features, respectively, may cause the loss of critical textual knowledge. This paper proposes a new type of structure tree for sentence representation, which exploits both syntactic (structural) and semantic information known as the weight vector dependency tree (WVD-tree). WVD-tree comprises structure trees with syntactic information along with word vectors representing semantic information of the sentences. Further, Gaussian attention weight is proposed for better capturing important semantic features of sentences. Meanwhile, we design an enhanced tree kernel to calculate the common parts between two structures for similarity judgment. Finally, WVD-tree is tested on widely used semantic textual similarity tasks. The experimental results prove that WVD-tree can effectively improve the accuracy of sentence similarity judgments

Cross-Linking of Thiolated Paclitaxel-Oligo(p-phenylene vinylene) Conjugates Aggregates inside Tumor Cells Leads to "Chemical Locks" That Increase Drug Efficacy

How to reduce the resistance of certain tumor cells to paclitaxel (PTX) and related taxoid anticancer drugs is a major challenge for improving cure rates. An oligo(p-phenylenevinylene) unit with thiol groups and a PTX unit (OPV-S-PTX), which enhances drug efficacy and reverses resistance is thus designed. The mechanism involves diffusion of OPV-S-PTX into the cell, where pi-pi interactions lead to aggregation. Cross-linking of the aggregates via oxidation of thiol groups is favored in tumor cells because of the higher reactive oxygen species (ROS) concentration. Cross-linked aggregates &quot;chemically lock&quot; the multichromophore particle for a more persistent effect. The IC50 of OPV-S-PTX for tumor cell line A549 is reduced down to 0.33 x 10(-9) M from that observed for PTX itself (41 x 10(-9) M). Enhanced efficacy by OPV-S-PTX is proposed to proceed via acceleration of microtubule bundle formation. A549/T-inoculated xenograft mice experiments reveal suppression of tumor growth upon OPV-S-PTX treatment. Altogether, these results show that the internal cross-linking of OPV-S-PTX through ROS provides a means to discriminate between tumor and healthy cells and the formation of the chemically locked particles enhances drug efficacy and helps in reducing resistance.</p

Molecular Characterization of the Complete Genome of Three Basal-BR Isolates of Turnip mosaic virus Infecting Raphanus sativus in China

Turnip mosaic virus (TuMV) infects crops of plant species in the family Brassicaceae worldwide. TuMV isolates were clustered to five lineages corresponding to basal-B, basal-BR, Asian-BR, world-B and OMs. Here, we determined the complete genome sequences of three TuMV basal-BR isolates infecting radish from Shandong and Jilin Provinces in China. Their genomes were all composed of 9833 nucleotides, excluding the 3′-terminal poly(A) tail. They contained two open reading frames (ORFs), with the large one encoding a polyprotein of 3164 amino acids and the small overlapping ORF encoding a PIPO protein of 61 amino acids, which contained the typically conserved motifs found in members of the genus Potyvirus. In pairwise comparison with 30 other TuMV genome sequences, these three isolates shared their highest identities with isolates from Eurasian countries (Germany, Italy, Turkey and China). Recombination analysis showed that the three isolates in this study had no “clear” recombination. The analyses of conserved amino acids changed between groups showed that the codons in the TuMV out group (OGp) and OMs group were the same at three codon sites (852, 1006, 1548), and the other TuMV groups (basal-B, basal-BR, Asian-BR, world-B) were different. This pattern suggests that the codon in the OMs progenitor did not change but that in the other TuMV groups the progenitor sequence did change at divergence. Genetic diversity analyses indicate that the PIPO gene was under the highest selection pressure and the selection pressure on P3N-PIPO and P3 was almost the same. It suggests that most of the selection pressure on P3 was probably imposed through P3N-PIPO

Supramolecular Hydrogel-Wrapped Gingival Mesenchymal Stem Cells in Cutaneous Radiation Injury

Radiation-induced skin wound/dermatitis is one of the common side effects of radiotherapy or interventional radiobiology. Gingiva-derived mesenchymal stem cells (GMSCs) were indicated to have therapeutic potentials in skin diseases. However, stem cells are prone to spread and difficult to stay in the skin for a long time, limiting their curative effects and application. This study investigated the therapeutic efficacy of Nap-GDFDFpDY (pY-Gel) self-assembled peptide hydrogel-encapsulated GMSCs to treat 137Cs γ-radiation-induced skin wounds in mice. The effects were evaluated by skin damage score, hind limb extension measurement and histological and immunohistochemical analysis. In vivo studies showed that pY-Gel self-assembled peptide hydrogel-encapsulated GMSCs could effectively improve wound healing in irradiated skin tissues. In addition, it was found that GMSCs conditioned medium (CM) could promote the proliferation, migration and DNA damage repair ability of skin cells after irradiation in human keratinocyte cell line HaCaT and normal human dermal fibroblasts (HFF). Mechanistically, GMSCs-CM can promote the expression of epidermal growth factor receptor (EGFR), signal transducers and activators of transcription 3 (STAT3) and matrix metalloproteinases (MMPs), suggesting that activation of the EGFR/STAT3 signaling pathway may be involved in the repair of skin cells after exposure to radiations. In conclusion, pY-Gel self-assembled peptide hydrogel-encapsulated GMSCs have a beneficial therapeutic effect on radiation-induced cutaneous injury and may serve as a basis of novel cells therapeutic approach