The versatility of palladium systems: from palladacycles to cyclic peptides and beyond

This work started with the aim to synthesize monomeric ring-opened analogues of the palladacycles [(iminoisoidoline)PdCl(PCy3)] incorporating iminoisoindoline and phosphine ligands, and evaluate their catalytic activities in C-C coupling reactions compared to their monomeric palladacyclic precursors. This project further evolved to investigate cyclic peptides derived from flaxseed oil as alternative ligands in palladium coordination chemistry for applications in C-C coupling reactions. During the course of our studies, we observed that cyclic peptides derived from flaxseed oil had a high affinity for first row transition metals

Weighted Trace-Penalty Minimization for Full Configuration Interaction

A novel unconstrained optimization model named weighted trace-penalty minimization (WTPM) is proposed to address the extreme eigenvalue problem arising from the Full Configuration Interaction (FCI) method. Theoretical analysis shows that the global minimizers of the WTPM objective function are the desired eigenvectors, rather than the eigenspace. Analyzing the condition number of the Hessian operator in detail contributes to the determination of a near-optimal weight matrix. With the sparse feature of FCI matrices in mind, the coordinate descent (CD) method is adapted to WTPM and results in WTPM-CD method. The reduction of computational and storage costs in each iteration shows the efficiency of the proposed algorithm. Finally, the numerical experiments demonstrate the capability to address large-scale FCI matrices

Integrating Higher-Order Dynamics and Roadway-Compliance into Constrained ILQR-based Trajectory Planning for Autonomous Vehicles

This paper addresses the advancements in on-road trajectory planning for Autonomous Passenger Vehicles (APV). Trajectory planning aims to produce a globally optimal route for APVs, considering various factors such as vehicle dynamics, constraints, and detected obstacles. Traditional techniques involve a combination of sampling methods followed by optimization algorithms, where the former ensures global awareness and the latter refines for local optima. Notably, the Constrained Iterative Linear Quadratic Regulator (CILQR) optimization algorithm has recently emerged, adapted for APV systems, emphasizing improved safety and comfort. However, existing implementations utilizing the vehicle bicycle kinematic model may not guarantee controllable trajectories. We augment this model by incorporating higher-order terms, including the first and second-order derivatives of curvature and longitudinal jerk. This inclusion facilitates a richer representation in our cost and constraint design. We also address roadway compliance, emphasizing adherence to lane boundaries and directions, which past work often overlooked. Lastly, we adopt a relaxed logarithmic barrier function to address the CILQR's dependency on feasible initial trajectories. The proposed methodology is then validated through simulation and real-world experiment driving scenes in real time.Comment: 6 pages, 3 figure

Preparation, biological characterization and preliminary human imaging studies of 68Ga-DOTA-IBA

PurposeIn this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA.MethodsThe controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions.ResultsThe prepared 68Ga-DOTA-IBA had a radiochemical purity of >97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio.Conclusions68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease

Expression and clinical value of CXCR4 in high grade gastroenteropancreatic neuroendocrine neoplasms

BackgroundCXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4.MethodsThis study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis.Results100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P<0.001), and Carcinoembryonic Antigen (CEA) elevation (P=0.008) between neuroendocrine tumor (NET) G3 and neuroendocrine carcinoma (NEC). CXCR4 was highly expressed only in tumors, low or no expressed in adjacent tissues (P<0.001). The expression level of CXCR4 in NEC was significantly higher than that in NET G3 (P=0.038). The K-M curves showed that there was no significant difference in overall survival between patients with high CXCR4 expression and patients with low CXCR4 expression, either in GEP-NEN G3 or NEC (P=0.920, P=0.842. respectively).ConclusionDifferential expression of CXCR4 was found between tumor and adjacent tissues and between NET G3 and NEC. Our results demonstrated that CXCR4 can be served as a new IHC diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multi-center, large sample size and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis

A Horizontal Distribution Model of Static Ice Cover Generated by Static and Dynamic Water Considering the Heat Transfer of Riverbanks

The thermal factor is the main reason for winter ice cover with a low Froude number flow, and the heat transfer to narrow and deep river banks accelerates ice cover formation and ice thickness change. The freezing of water flow to freezing thickening is a nonisothermal-flow phase transition process coupled with the water flow temperature, environment and riverbank. Here, the Nusselt number and viscous dissipation are used to consider the flow velocity influence on icing, and a thermodynamic model of static ice cover horizontal distribution considering riverbed heat transfer is established. The initial ice time, freezing time and static ice cover thickness formed by static and dynamic water calculated by the model were consistent with measured data. The model reflects the horizontal growth process of the static ice cover, which was significant for narrow and deep channels. The horizontal distribution of the static ice cover was thin in the center and thick on both sides. The maximum horizontal thickness difference of −20 °C indoor freezing for 24 h reached 15% of the central ice thickness. Compared with the degree-day method for calculating ice thickness, the numerical model and dimensionless formula better reflect the growth law and horizontal distribution characteristics of static ice cover and provide a theoretical basis for safe water conveyance under ice cover in winter and ice cover formation in reservoirs and lakes in cold regions

Myrothecols G and H, Two New Analogues of the Marine-Derived Quinone Sesquiterpene Penicilliumin A

Two new quinone sesquiterpenes named myrothecols G and H (1 and 2), a pair of C-1′ diastereomers of 13-hydroxyl penicilliumin A, were isolated from the mycelia solid cultures of Myrothecium sp. SC0265. Their structures, including the absolute configurations, were established on the basis of the spectroscopic data combining with the theoretical conformational analysis. The cytotoxic activities of 1 and 2 were tested against a panel of human tumor cell lines

Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats

Summary: Previous research has demonstrated significant differences in intestinal flora between pregnant women with intrahepatic cholestasis of pregnancy (ICP) and healthy pregnant women. The objective of our study is to identify the key bacteria involved in ICP rats and explore the underlying mechanism. We established an ICP rat model and collected rat feces for metagenomic sequencing and found that Roseburia intestinalis (R.I) is the key bacteria in ICP. Transplantation of R.I improved phenotypes associated with ICP through the bile acid/farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling pathway. We used the FXR antagonist Z-Guggulsterone (Z-Gu) to verify the key role of FXR in ICP and found that Z-Gu reversed the benefits of R.I on ICP rats. Our research highlights the important role of intestinal flora in the pathogenesis of ICP and provides a novel approach for its treatment

Xylaropyrones B and C, new gamma-pyrones from the endophytic fungus Xylaria sp SC1440

Two new -pyrones, xylaropyrones B (1) and C (2), together with three known compounds, xylaropyrone (3), annularin A (4) and annularin C (5), were isolated from solid cultures of the endophytic fungus Xylaria sp. SC1440. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data. The relative configurations of 1 and 2 were assigned on the basis of J-based configurational analysis, and the absolute configurations were established by experimental and TDDFT calculated ECD spectra. The isolated compounds were evaluated for cytotoxic and tyrosinase inhibitory activity. [GRAPHICS]