Productive Poplar Genotypes Exhibited Temporally Stable Low Stem Embolism Resistance and Hydraulic Resistance Segmentation at the Stem-Leaf Transition.

Breeding tree genotypes that are both productive and drought-resistant is a primary goal in forestry. However, the relationships between plant hydraulics and yield at the genotype level, and their temporal stabilities, remain unclear. We selected six poplar genotypes from I-101 (Populus alba) × 84 K (P. alba × Popolus tremula var. glandulosa) for experiments in the first and fourth years after planting in a common garden. Measurements included stem embolism resistance, shoot hydraulic resistance and its partitioning between stems and leaves, vessel- and pit-level anatomy, leaf carbon acquisition capacity, carbon allocation to leaves, and aboveground biomass (yield proxy). Significant genetic variations in hydraulic properties and yield were found among genotypes in both years. Productive genotypes had wide vessels, large thin pit membranes, small pit apertures, and shallow pit chambers. Hydraulic resistance was negatively correlated with yield, enabling high stomatal conductance and assimilation rates. Productive genotypes allocated less aboveground carbon and hydraulic resistance to leaves. Temporally stable trade-offs between stem embolism resistance and yield, and between hydraulic segmentation and yield, were identified. These findings highlight the tight link between hydraulic function and yield and suggest that stable trade-offs may challenge breeding poplar genotypes that are both productive and drought-resistant.

The phytopathogen Xanthomonas campestris senses and effluxes salicylic acid via a sensor HepR and an RND family efflux pump to promote virulence in host plants.

Salicylic acid (SA) plays an essential role in plant defense against biotrophic and semi-biotrophic pathogens. Following pathogen recognition, SA biosynthesis dramatically increases at the infection site of the host plant. The manner in which pathogens sense and tolerate the onslaught of SA stress to survive in the plant following infection remains to be understood. The objective of this work was to determine how the model phytopathogen Xanthomonas campestris pv. campestris (Xcc) senses and effluxes SA during infection inside host plants. First, RNA-Seq analysis identified an SA-responsive operon Xcc4167-Xcc4171, encoding a MarR family transcription factor HepR and an RND (resistance-nodulation-cell division) family efflux pump HepABCD in Xcc. Electrophoretic mobility shift assays and DNase I footprint analysis revealed that HepR negatively regulated hepABCD expression by specifically binding to an AT-rich region of the promoter of the hepRABCD operon, Phep. Second, isothermal titration calorimetry and further genetic analysis suggest that HepR is a novel SA sensor. SA binding released HepR from its cognate promoter Phep and then induced the expression of hepABCD. Third, the RND family efflux pump HepABCD was responsible for SA efflux. The hepRABCD cluster was also involved in the regulation of culture pH and quorum sensing signal diffusible signaling factor turnover. Finally, the hepRABCD cluster was transcribed during the XC1 infection of Chinese radish and was required for the full virulence of Xcc in Chinese radish and cabbage. These findings suggest that the ability of Xcc to co-opt the plant defense signal SA to activate the multidrug efflux pump may have evolved to ensure Xcc survival and virulence in susceptible host plants.

Gold Self-Relay Catalysis Enabling Regioselective Bicyclization toward [5]Azahelicenes.

A gold self-relay catalysis driving a double annulation cascade starting from soft electron-biased 1,2-di(o-aminoaryl)alkynes and aldehydes is reported, enabling regioselective access to produce a series of [5]azahelicenes depending on the substitution pattern in generally good yields under mild conditions. This protocol exploits and unifies the π- and σ-Lewis acid capability of gold catalysts, featuring high molecular convergence, broad substrate flexibility, and good functional group compatibility and regioselectivity.

Protocol for culturing patient-derived organoids of cervical cancer.

Herein, we present a protocol for culturing patient-derived organoids (PDOs) of cervical cancer that includes workflows for tumor biopsy/resection tissue and cytobrush-sampled cells. We describe steps for PDO culture initiation, including rinsing, gentle dissociation, Lymphoprep separation, and cell assessment, as well as seeding cells from surgical and cytobrush tissue digestion. We then provide guidance on PDO maintenance and passage and techniques for producing conditioned medium. Overall, this protocol serves as a valuable guide for establishing and maintaining cervical cancer PDOs. For complete details on the use and execution of this protocol, please refer to Colbert et al.1.

Dynamic Analysis of the Fruit Sugar-Acid Profile in a Fresh-Sweet Mutant and Wild Type in 'Shatangju' (Citrus reticulata cv.).

Citrate is a major determinant of fruit flavor quality. Currently, citrus species and/or varieties with significant alterations in citrate level have greatly advanced the molecular basis of citrate accumulation in fruit. However, in-depth dissections of the molecular mechanism specific to citrate accumulation are still limited due to the lack of mutants, especially within one single variety. In this study, a fresh-sweet 'Shatangju' mutant (Citrus reticulata cv.) was obtained during a survey of citrus resources in Guangdong, China, and the phenotype, fruit morphology, and primary flavor profiles were comparatively analyzed. Unlike the wild-type 'Shatangju' (WT), the mutant (MT) material exhibited a dwarfed and multi-branched tree shape, delayed flowering and fruit ripening at maturity, a prolonged fruit tree-retention time, and a decreased single fruit weight at maturity. Dynamic measurement of the metabolite levels further suggested that the contents and fluctuation patterns of vitamin C, malate, quinate, and oxalate showed no obvious difference between MT and MT fruits, while the citrate level in MT fruits significantly decreased over various developmental stages, ranging from 0.356 to 1.91 mg g-1 FW. In addition, the accumulation patterns of the major soluble sugars (sucrose, fructose, and glucose), as well as the sugar/acid ratio, were also altered in MT fruits during development. Taken together, this study provides a novel acid-free 'Shatangju' mutant, which can serve as a powerful tool for the research of fruit flavor quality, especially for the comprehensive understanding of the molecular mechanism of citrate accumulation in fruits.

Phase I clinical trial evaluating the safety, tolerance, pharmacokinetics and pharmacodynamics of HSK21542 injection in healthy volunteers.

HSK21542 injection is a new peripheral kappa opioid receptor (KOR) agonist. To evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics, this study was conducted in healthy volunteers, consisting of two parts: a single ascending dose (0.2-3.375 µg/kg, 15-min infusion) and different infusion durations (0.2 and 1 µg/kg, 2- or 15-min infusion). The area under the plasma concentration-time curve (AUC) and peak concentration (Cmax) of HSK21542 were dose-linear among 0.2-3.375 µg/kg. After intravenous injection, HSK21542 was rapidly eliminated with a half-life (t1/2) of 1.5 h, and the majority (48.02%) of the dose was excreted unchanged in urine. Pharmacodynamic results showed that HSK21542 increased prolactin release and reached a peak at 1-2 h after administration but had no significant effect on vasopressin levels. There was a brief increase in urine volume within the initial 2 h after administration. HSK21542 was well tolerated; most of the adverse effects (AEs) in the trial group were grade 1, and only 2 cases (4.0%) were grade 2. The main AE was paresthesia, which appeared in 42% (21/50) in the trial group. No serious adverse event (SAE) was observed. No subject withdrew early due to AEs. These results suggest that HSK21542 may be a potential treatment for pain and pruritic conditions.

Anoikis in prostate cancer bone metastasis gene signatures and therapeutic implications.

Background: Bone metastasis from prostate cancer severely impacts patient outcomes and quality of life. Anoikis, a form of programmed cell death triggered by the loss of cell-matrix interactions, plays a critical role in cancer progression. However, its precise relationship with prostate cancer-induced bone metastasis remains unclear. This study aims to elucidate this relationship, focusing on anoikis-related gene signatures, molecular pathways, and therapeutic implications. Methods: We used the TCGA-PRAD dataset for training, with MSKCC and GSE70769 as validation cohorts. To evaluate immunotherapy efficacy, we examined IMvigor 210 and GSE91016 datasets, and GSE137829 provided single-cell insights into prostate cancer. Specific anoikis-related genes (ARGs) were identified, and Random Survival Forest analysis and multivariate Cox regression were employed to develop anoikis-linked features. The 'clustanoikisProfilanoikis' and 'GSEA' packages were used to explore potential ARG-related pathways. Results: Analyzing 553 samples from TCGA, 231 from MSKCC, 94 from GSE70769, and single-cell data from 6 prostate cancer patients (GSE137829), we constructed a prognostic model based on 9 ARGs. GSVA revealed upregulation of carcinogenic pathways, including epithelial-mesenchymal transition, E2F targets, and angiogenesis, with downregulation of metabolic pathways. Significant differences in somatic mutations were observed between cohorts, with a positive correlation between anoikis scores and tumor mutational burden (TMB). Immune landscape analysis suggested high-risk patients might benefit more from chemotherapy than immunotherapy based on their risk score. Single-cell analysis indicated overactivation of carcinogenic pathways in the high anoikis score group. Conclusion: This study elucidates the complex interplay between anoikis and bone metastasis in prostate cancer. Our findings highlight the critical role of anoikis in metastatic progression, enhancing the understanding of key biomarkers and molecular dynamics. The identified anoikis-related gene signatures and disrupted pathways offer promising avenues for predictive and therapeutic strategies in prostate cancer management.

The variation of resistome, mobilome and pathogen in domestic and industrial wastewater treatment systems.

Wastewater treatment plants (WWTPs), including both domestic and industrial facilities, are key contributors to antibiotic resistance genes (ARGs) and human pathogens in the environment. However, the characteristics and dissemination mechanisms of ARGs in domestic (SD) and industrial (SI) wastewater treatment systems remain unclear, leading to uncertainties in risk assessment. Based on metagenomic analysis, we observed significant differences in the compositions of resistome (ARGs and metal resistance genes, MRGs), mobilome (mobile genetic elements, MGEs), and bacterial community between SD and SI. SI exhibited lower diversity of ARGs but higher abundance of MRGs compared to SD. The removal efficiency of resistome was lower in the SI than that in the SD. MGEs emerged as the primary driver of ARG dissemination in the WWTPs, followed by the bacterial community. Environmental conditions (physicochemical parameters, heavy metals, and antibiotics) indirectly influenced the variation of resistome. Significantly, environmental conditions and MGEs highly influenced the composition of resistome in the SI, while bacterial community more associated with resistome in the SD. Additionally, we identified 36 human bacterial pathogens as potential hosts of ARGs, MRGs, and MGEs in wastewater samples. This study provides new insights on the dissemination mechanisms and risk assessment of antimicrobial resistance in the different types of WWTPs.

Identified a novel prognostic model of HCC basing on virus signature for guiding immunotherapy.

Oncolytic viral immunotherapy is a cancer treatment that uses native or genetically modified viruses that selectively replicate and destroy tumor cells. In this study, we aimed to construct a virus-based prognostic model for risk assessment and prognosis prediction in patients with hepatocellular carcinoma (HCC) and determine the most appropriate virus as a candidate vector for oncolytic virus immunotherapy. Microbiome and RNA sequencing data and clinical information were obtained from The Cancer Genome Atlas, and viruses with prognostic value were identified (Deltabaculovirus, Sicinivirus, and Cytomegalovirus) to construct the prognostic model. Correlation analyses were performed to evaluate the predictive function of the viral signature. Bioinformatics analyses were conducted to explore the functional enrichment of viral expression in HCC. The risk score generated by this model could distinguish patients with different survival outcomes, have excellent reliability and accuracy, and could be used as an independent prognostic indicator. The high-risk score group showed significantly lower overall survival, and this trend was also observed in subgroups with different clinicopathological features. Furthermore, Deltabaculovirus positively correlated with amino acid metabolism, energy metabolism signaling pathways, peroxisomes, and complement coagulation cascades. In addition, Deltabaculovirus was significantly related to immune cell infiltration; therefore, patients with high Delta-baculovirus expression might respond better to HCC immunotherapy. Our study identified a promising predictive viral signature for assessing clinical prognosis and guiding immunotherapy in HCC. Deltabaculovirus might be a suitable viral vector for oncolytic virus immunotherapy.

Perioperative and mid-term outcomes of robotic-assisted versus video-assisted minimally invasive esophagectomy for esophageal cancer: a retrospective propensity-matched analysis of 842 patients.

Aim: Comparing the safety, effectiveness, and mid-term survival rates of robot-assisted minimally invasive esophagectomy (RAMIE) and video-assisted minimally invasive esophagectomy (VAMIE). Methods: A total of 842 patients undergoing minimally invasive esophagectomy were analyzed, including 694 patients in VAMIE group and 148 in RAMIE group. PSM analysis was applied to generate matched pairs for further comparison. Operative outcomes, postoperative complications and Mid-term outcomes were compared between all patients in matched groups. Results: After 1:4 PSM, 148 patients in the RAMIE and 592 patients in the VAMIE. Compared to VAMIE, RAMIE exhibited earlier removal of chest and neck drainage tubes, shorter postoperative hospital stays, and a higher number of lymph node dissections. However, the surgical duration of RAMIE was longer than that of VAMIE. Postoperative complications were no statistically significant between the RAMIE and VAMIE groups. There was no statistically significant difference in the 3-year OS and DFS between the two groups. Conclusion: Compared to VAMIE, RAMIE emerges as a viable and safe surgical approach and suggests RAMIE as a potential alternative to minimally invasive esophagectomy.

Bioactive components in prunella vulgaris for treating Hashimoto's disease via regulation of innate immune response in human thyrocytes.

Background: Hashimoto's thyroiditis (HT) is a thyroid autoimmune disease characterized by lymphocytic infiltration and thyroid destruction. Prunella vulgaris (PV) is a traditional Chinese herbal medicine with documented clinical efficacy in treating HT. We previously reported an immunoregulatory effect of PV in thyrocytes; however, the bioactive components of PV remained unclear. This study aimed to elucidate key components of PV for treating HT and their acting mechanisms. Methods: Network pharmacology was used to predict key PV components for HT. The predicted components were tested to determine whether they could exert an immunoregulatory effect of PV in human thyrocytes. Limited proteolysis-mass spectrometry (Lip-MS) was used to explore interacting proteins with PV components in human thyrocytes. Microscale thermophoresis binding assay was used to evaluate the affinity of PV components with the target protein. Results: Eleven PV components with 192 component targets and 3415 HT-related genes were gathered from public databases. With network pharmacology, a 'component-target-disease' network was established wherein four flavonoids including quercetin, luteolin, kaempferol, morin, and a phytosterol, ß-sitosterol were predicted as key components in PV for HT. In stimulated primary human thyrocytes or Nthy-ori-31 cells, key components inhibited gene expressions of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interferon-ß (IFN-ß), cellular apoptosis, and activation of nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3). Heat shock protein 90 alpha, class A, member 1 (HSP90AA1), was identified to interact with flavonoids in PV by Lip-MS. Morin had the highest affinity with HSP90AA1 (KD = 122.74 µM), followed by kaempferol (KD = 168.53 µM), luteolin (KD = 293.94 µM), and quercetin (KD = 356.86 µM). Conclusion: Quercetin, luteolin, kaempferol, morin, and ß-sitosterol reproduced an anti-inflammatory and anti-apoptosis effect of PV in stimulated human thyrocytes, which potentially contributed to the treatment efficacy of PV in HT.

Identification of a recessive gene RgM4G52 conferring red glume, stem, and rachis in a Triticum boeoticum mutant.

Anthocyanins are plant secondary metabolites belonging to the polyphenol class of natural water-soluble phytopigments. The accumulation of anthocyanins in different plant tissues can improve plant survival under adverse conditions. In addition, plants with the resulting colorful morphology can be utilized as landscape plants. Triticum boeoticum (syn. Triticum monococcum ssp. aegilopoides, 2n=2x=14, AbAb) serves as a valuable genetic resource for the improvement of its close relative common wheat in terms of enhancing resilience to various biotic and abiotic stresses. In our previous study, the EMS-mutagenized mutant Z2921 with a red glume, stem, and rachis was generated from T. boeoticum G52, which has a green glume, stem, and rachis. In this study, the F1, F2, and F2:3 generations of a cross between mutant-type Z2921 and wild-type G52 were developed. A single recessive gene, tentatively designated RgM4G52, was identified in Z2921 via genetic analysis. Using bulked segregant exome capture sequencing (BSE-Seq) analysis, RgM4G52 was mapped to chromosome 6AL and was flanked by the markers KASP-58 and KASP-26 within a 3.40-cM genetic interval corresponding to 1.71-Mb and 1.61-Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Triticum boeoticum (TA299) reference genomes, respectively, in which seven and four genes related to anthocyanin synthesis development were annotated. Unlike previously reported color morphology-related genes, RgM4G52 is a recessive gene that can simultaneously control the color of glumes, stems, and rachis in wild einkorn. In addition, a synthetic Triticum dicoccum-T. boeoticum amphiploid Syn-ABAb-34, derived from the colchicine treatment of F1 hybrids between tetraploid wheat PI 352367 (T. dicoccum, AABB) and Z2921, expressed the red stems of Z2921. The flanking markers of RgM4G52 developed in this study could be useful for developing additional common wheat lines with red stems, laying the foundation for marker-assisted breeding and the fine mapping of RgM4G52.

Multiple applications of metal-organic frameworks (MOFs) in the treatment of orthopedic diseases.

Pharmacologic treatment of orthopedic diseases is a common challenge for clinical orthopedic surgeons, and as an important step in the stepwise treatment of orthopedic diseases, it is often difficult to achieve satisfactory results with existing pharmacologic treatments. Therefore, it is increasingly important to find new ways to effectively improve the treatment pattern of orthopedic diseases as well as to enhance the therapeutic efficacy. It has been found that metal-organic frameworks (MOFs) possess the advantages of high specific surface area, high porosity, chemical stability, tunability of structure and biocompatibility. Therefore, MOFs are expected to improve the conventional traditional treatment modality for bone diseases. This manuscript reviewed the applications of MOFs in the treatment of common clinical bone diseases and look forward to its future development.

AB044. Leptomeningeal metastatic esthesioneuroblastoma: a systematic review with case illustration.

BACKGROUND: Esthesioneuroblastomas (ENBs) represent a rare subset of malignancies originating within the upper aerodigestive tract, characterized by a propensity for local metastasis to the intracranial compartment through the cribriform plate. These neoplasms are frequently associated with a high incidence of local recurrence subsequent to therapeutic intervention. In this report, we review the literature and present a case of a patient with extensive meningeal and leptomeningeal dissemination of ENB, with a survival period of 2 years. METHODS: A systematic review of literature was conducted in accordance with the PRISMA guidelines. Additionally, the presentation, surgical management, chemotherapy, and outcomes of a 60-year-old female presenting with extensive meningeal metastasis at onset. RESULTS: Following the literature review, 43 distinct works were identified, extracted variables from the remaining seven papers that met our inclusion criteria included demographic data, presenting symptoms, recurrence status, primary tumor location, location of Leptomeningeal metastasis of ENB, interval from initial treatment to recurrence, initial treatment approach, treatment-related complications, survival outcomes, and post-treatment status of patients. The average age at diagnosis was 52.6 years (range, 31-76 years), with females comprising 63.6% of the sample. The majority underwent gross-total resection and received adjuvant radiotherapy as initial therapy. The median time to intracranial metastasis was 57 months post-primary tumor diagnosis. The median overall survival for ENB with intracranial metastasis was 14 months. CONCLUSIONS: ENB exhibits a marked propensity for recurrence and can metastasize to the intracranial space years post-remission, which correlates with reduced survival. Therefore, perpetual radiographic surveillance is warranted for all ENB patients to detect late recurrences and intracranial spread promptly.

Bone scaffolds-based localized drugs delivery for osteosarcoma: current status and future perspective.

A common malignant bone neoplasm in teenagers is Osteosarcoma. Chemotherapy, surgical therapy, and radiation therapy together comprise the usual clinical course of treatment for Osteosarcoma. While Osteosarcoma and other bone tumors are typically treated surgically, however, surgical resection frequently fails to completely eradicate tumors, and in turn becomes the primary reason for postoperative recurrence and metastasis, ultimately leading to a high rate of mortality. Patients still require radiation and/or chemotherapy after surgery to stop the spread of the tumor and its metastases, and both treatments have an adverse influence on the body's organ systems. In the postoperative management of osteosarcoma, bone scaffolds can load cargos (growth factors or drugs) and function as drug delivery systems (DDSs). This review describes the different kinds of bone scaffolds that are currently available and highlights key studies that use scaffolds as DDSs for the treatment of osteosarcomas. The discussion also includes difficulties and perspectives regarding the use of scaffold-based DDSs. The study may serve as a source for outlining efficient and secure postoperative osteosarcoma treatment plans.

Itm2a expression marks periosteal skeletal stem cells that contribute to bone fracture healing.

The periosteum contains skeletal stem/progenitor cells that contribute to bone fracture healing. However, the in vivo identity of periosteal skeletal stem cells (P-SSCs) remains unclear, and membrane protein markers of P-SSCs that facilitate tissue engineering are needed. Here, we identified integral membrane protein 2A (Itm2a) enriched in SSCs using single-cell transcriptomics. Itm2a+ P-SSCs displayed clonal multipotency and self-renewal and sat at the apex of their differentiation hierarchy. Lineage-tracing experiments showed that Itm2a selectively labeled the periosteum and that Itm2a+ cells were preferentially located in the outer fibrous layer of the periosteum. The Itm2a+ cells rarely expressed CD34 or Osx, but expressed periosteal markers such as Ctsk, CD51, PDGFRA, Sca1, and Gli1. Itm2a+ P-SSCs contributed to osteoblasts, chondrocytes, and marrow stromal cells upon injury. Genetic lineage tracing using dual recombinases showed that Itm2a and Prrx1 lineage cells generated spatially separated subsets of chondrocytes and osteoblasts during fracture healing. Bone morphogenetic protein 2 (Bmp2) deficiency or ablation of Itm2a+ P-SSCs resulted in defects in fracture healing. ITM2A+ P-SSCs were also present in the human periosteum. Thus, our study identified a membrane protein marker that labels P-SSCs, providing an attractive target for drug and cellular therapy for skeletal disorders.

Efficacy of Foldable Capsular Vitreous Body Implants Filled With Light or Heavy Silicone Oil in the Treatment of Silicone Oil-dependent Eyes.

Purpose: The purpose of this study was to compare the clinical efficacy of foldable capsular vitreous body (FCVB) filled with either light or heavy silicone oil and the incidence of complications after their implantation for the treatment of severe ocular trauma and silicone oil-dependent eyes. Methods: FCVB filled with either light (n = 16) or heavy (n = 8) silicone oil was implanted in 24 patients. During the 12-month follow-up period, the intraocular pressure, final best-corrected visual acuity, retinal reattachment condition, position of the FCVB, and complications were assessed. Results: All surgeries were performed without issue. There was no significant difference in preoperative and postoperative best-corrected visual acuity between the two groups. A significant improvement in the intraocular pressure was observed after surgery in both the light silicone oil (P = 0.029) and heavy silicone oil (P = 0.035) groups. None of the patients developed displacement or prolapse of the FCVB. The most common early and late postoperative complications were postoperative hemorrhage (33.3%) and corneal opacification (50%), respectively. Conclusions: FCVB filled with heavy silicone oil can be used as a supplemental therapy for patients who have lost the anterior segment of their eye, have lesions of the inferior retina, or cannot maintain the prone position for various reasons. Translational Relevance: Implantation of FCVB combined with heavy silicone oil compensates for the shortcomings of this with light silicone oil, providing patients with more personalized treatment.

Machine-learning-based prediction by stacking ensemble strategy for surgical outcomes in patients with degenerative cervical myelopathy.

BACKGROUND: Machine learning (ML) is extensively employed for forecasting the outcome of various illnesses. The objective of the study was to develop ML based classifiers using a stacking ensemble strategy to predict the Japanese Orthopedic Association (JOA) recovery rate for patients with degenerative cervical myelopathy (DCM). METHODS: A total of 672 patients with DCM were included in the study and labeled with JOA recovery rate by 1-year follow-up. All data were collected during 2012-2023 and were randomly divided into training and testing (8:2) sub-datasets. A total of 91 initial ML classifiers were developed, and the top 3 initial classifiers with the best performance were further stacked into an ensemble classifier with a supported vector machine (SVM) classifier. The area under the curve (AUC) was the main indicator to assess the prediction performance of all classifiers. The primary predicted outcome was the JOA recovery rate. RESULTS: By applying an ensemble learning strategy (e.g., stacking), the accuracy of the ML classifier improved following combining three widely used ML models (e.g., RFE-SVM, EmbeddingLR-LR, and RFE-AdaBoost). Decision curve analysis showed the merits of the ensemble classifiers, as the curves of the top 3 initial classifiers varied a lot in predicting JOA recovery rate in DCM patients. CONCLUSIONS: The ensemble classifiers successfully predict the JOA recovery rate in DCM patients, which showed a high potential for assisting physicians in managing DCM patients and making full use of medical resources.

Overexpression of DUSP26 gene suppressed the proliferation, migration, and invasion of human prostate cancer cells.

Prostate cancer (PCa) is threatening the health of millions of people, the pathological mechanism of prostate cancer has not been fully elaborated, and needs to be further explored. Here, we found that the expression of DUSP26 is dramatically suppressed, and a positive connection of its expression with PCa prognosis was also observed. In vitro, overexpression of DUSP26 significantly inhibited the proliferative, migrative, and invasive capacities of PC3 cells, DUSP26 silencing presented opposite results. Tumor formation experiments in subcutaneous nude mice demonstrated that DUSP26 overexpression could significantly suppress PC3 growth in vivo. Moreover, the mechanism of DUSP26 gene and PCa was discovered by RNA-Seq analysis. We found that DUSP26 significantly inhibited MAPK signaling pathway activation, and further experiments displayed that DUSP26 could impair TAK1, p38, and JNK phosphorylation. Interestingly, treatment with the TAK1 inhibitor (iTAK1) attenuated the effect of DUSP26 on PC3 cells. Together, these results suggested that DUSP26 may serve as a novel therapeutic target for PC3 cell type PCa, the underlying mechanism may be through TAK1-JNK/p38 signaling.

Cascade Cyclization of N-Cyanamide Alkenes for the Divergent Synthesis of Azido-, Nitro-, and Alkenyl-Containing Pyrroloquinazolinones.

Radical cascade cyclizations of N-cyanamide alkenes have been developed for the divergent synthesis of pyrroloquinazolinones bearing azido, alkenyl, and nitro groups by controlling the reaction conditions. The reaction temperature and the loading of the base play important roles in the different reaction pathways. These reactions are characterized by wide functional group compatibility and mild conditions.