Multi-Host Model-Based Identification of \u3ci\u3eArmillifer agkistrodontis\u3c/i\u3e (Pentastomida), a New Zoonotic Parasite from China

Background: Pentastomiasis is a rare parasitic infection of humans. Pentastomids are dioecious obligate parasites requiring multiple hosts to complete their life cycle. Despite their worm-like appearance, they are commonly placed into a separate sub-class of the subphylum Crustacea, phylum Arthropoda. However, their systematic position is not uncontested and historically, they have been considered as a separate phylum. Methodology/Principal Findings: An appraisal of Armillifer agkistrodontis was performed in terms of morphology and genetic identification after its lifecycle had been established in a multi-host model, that is, mice and rats as intermediate hosts, and snakes (Agkistrodon acutus and Python molurus) as definitive hosts. Different stages of the parasite, including eggs, larvae and adults, were isolated and examined morphologically using light and electron microscopes. Phylogenetic and cluster analysis were also undertaken, focusing on the 18S rRNA and the Cox1 gene. The time for lifecycle completion was about 14 months, including 4 months for the development of eggs to infectious larvae in the intermediate host and 10 months for infectious larvae to mature in the final host. The main morphological difference between A. armillatus and Linguatula serrata is the number of abdominal annuli. Based on the 18S rRNA sequence, the shortest hereditary distance was found between A. agkistrodontis and Raillietiella spp. The highest degree of homology in the Cox 1 nucleic acid sequences and predicted amino acid sequences was found between A. agkistrodontis and A. armillatus. Conclusion: This is the first time that a multi-host model of the entire lifecycle of A. agkistrodontis has been established. Morphologic and genetic analyses supported the notion that pentastomids should be placed into the phylum Arthropoda

Multi-host Model-Based Identification of Armillifer agkistrodontis (Pentastomida), a New Zoonotic Parasite from China

Little information is currently available on the lifecycle and morphology of pentastomids, a new zoonotic parasite in China. The lifecycle of Armillifer agkistrodontis was established in multiple hosts, i.e., an intermediate host and a definitive host, and the parasite examined in terms of morphology and genetic relationship with other species. The time required for the completion of an entire lifecycle was about 14 months. The main morphological difference between A. armillatus and L. serrata is the number of abdominal annuli. The genetic data supported the notion that pentastomids belong to the phylum Arthropoda. Based on the 18S rRNA sequence, the shortest hereditary distance was found between A. agkistrodontis and Raillietiella spp. The highest similarity in the Cox 1 nucleic acid sequences was found between A. agkistrodontis and A. armillatus. The established multi-host model provides a possible approach to confirm suspected infections and offers an opportunity to further study this parasite

Large Language Models Empowered Agent-based Modeling and Simulation: A Survey and Perspectives

Agent-based modeling and simulation has evolved as a powerful tool for modeling complex systems, offering insights into emergent behaviors and interactions among diverse agents. Integrating large language models into agent-based modeling and simulation presents a promising avenue for enhancing simulation capabilities. This paper surveys the landscape of utilizing large language models in agent-based modeling and simulation, examining their challenges and promising future directions. In this survey, since this is an interdisciplinary field, we first introduce the background of agent-based modeling and simulation and large language model-empowered agents. We then discuss the motivation for applying large language models to agent-based simulation and systematically analyze the challenges in environment perception, human alignment, action generation, and evaluation. Most importantly, we provide a comprehensive overview of the recent works of large language model-empowered agent-based modeling and simulation in multiple scenarios, which can be divided into four domains: cyber, physical, social, and hybrid, covering simulation of both real-world and virtual environments. Finally, since this area is new and quickly evolving, we discuss the open problems and promising future directions.Comment: 37 page

Poly[μ3-hydroxido-μ-(pyridine-2,4,6-tricarboxyl­ato)-dilead(II)]

The asymmetric unit of the title coordination polymer, [Pb2(C8H2NO6)(OH)]n, contains two crystallographically independent PbII ions, one pyridine-2,4,6-tricarboxyl­ate (ptc) trianion and one hydroxide anion. One of the PbII atoms is coordinated by one pyridine N and four carboxyl­ate O atoms from the ptc trianion and a hydroxide O atom in a distorted octa­hedral geometry. The other PbII atom is five-coordinated by three carboxyl­ate O atoms and two hydroxide O atoms in a distorted tetra­gonal–pyramidal geometry. Four neighbouring PbII atoms are bridged through two μ3-hydroxide ligands, forming the centrosymmetric Pb4(OH)2 core. The three-dimensional structure is further achieved through bridging carboxyl­ate groups. There are also O—H⋯O hydrogen bonds between the hydroxide ligand and the carboxyl­ate group

The site conditions of the Guo Shou Jing Telescope

The weather at Xinglong Observing Station, where the Guo Shou Jing Telescope (GSJT) is located, is strongly affected by the monsoon climate in north-east China. The LAMOST survey strategy is constrained by these weather patterns. In this paper, we present a statistics on observing hours from 2004 to 2007, and the sky brightness, seeing, and sky transparency from 1995 to 2011 at the site. We investigate effects of the site conditions on the survey plan. Operable hours each month shows strong correlation with season: on average there are 8 operable hours per night available in December, but only 1-2 hours in July and August. The seeing and the sky transparency also vary with seasons. Although the seeing is worse in windy winters, and the atmospheric extinction is worse in the spring and summer, the site is adequate for the proposed scientific program of LAMOST survey. With a Monte Carlo simulation using historical data on the site condition, we find that the available observation hours constrain the survey footprint from 22h to 16h in right ascension; the sky brightness allows LAMOST to obtain the limit magnitude of V = 19.5mag with S/N = 10.Comment: 10 pages, 8 figures, accepted for publication in RA

Continuous low-dose cyclophosphamide plus prednisone in the treatment of relapsed and refractory multiple myeloma with severe complications

Background/objectiveWe retrospectively analyzed the effective and safety of continuous low-dose cyclophosphamide combined with prednisone (CP) in relapsed and refractory multiple myeloma (RRMM) patients with severe complications.MethodsA total of 130 RRMM patients with severe complications were enrolled in this study, among which 41 patients were further given bortezomib, lenalidomide, thalidomide or ixazomib on the basis of CP regimen (CP+X group). The response to therapy, adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were recorded.ResultsAmong the 130 patients, 128 patients received therapeutic response assessment, with a complete remission rate (CRR) and objective response rate (ORR) of 4.7% and 58.6%, respectively. The median OS and PFS time were (38.0 ± 3.6) and (22.9±5.2) months, respectively. The most common AEs were hyperglycemia (7.7%), pneumonia (6.2%) and Cushing’s syndrome (5.4%). In addition, we found the pro-BNP/BNP level was obviously decreased while the LVEF (left ventricular ejection fraction) was increased in RRMM patients following CP treatment as compared with those before treatment. Furthermore, CP+X regimen further improved the CRR compared with that before receiving the CP+X regimen (24.4% vs. 2.4%, P=0.007). Also, both the OS and PFS rates were significantly elevated in patients received CP+X regimen following CP regimen as compared with the patients received CP regimen only.ConclusionThis study demonstrates the metronomic chemotherapy regimen of CP is effective to RRMM patients with severe complications

Osteogenic differentiation of 3D-printed porous tantalum with nano-topographic modification for repairing craniofacial bone defects

Introduction: Congenital or acquired bone defects in the oral and cranio-maxillofacial (OCMF) regions can seriously affect the normal function and facial appearance of patients, and cause great harm to their physical and mental health. To achieve good bone defect repair results, the prosthesis requires good osteogenic ability, appropriate porosity, and precise three-dimensional shape. Tantalum (Ta) has better mechanical properties, osteogenic ability, and microstructure compared to Ti6Al4V, and has become a potential alternative material for bone repair. The bones in the OCMF region have unique shapes, and 3D printing technology is the preferred method for manufacturing personalized prosthesis with complex shapes and structures. The surface characteristics of materials, such as surface morphology, can affect the biological behavior of cells. Among them, nano-topographic surface modification can endow materials with unique surface properties such as wettability and large surface area, enhancing the adhesion of osteoblasts and thereby enhancing their osteogenic ability.Methods: This study used 3D-printed porous tantalum scaffolds, and constructed nano-topographic surface through hydrothermal treatment. Its osteogenic ability was verified through a series of in vitro and in vivo experiments.Results: The porous tantalum modified by nano-topographic surface can promote the proliferation and osteogenic differentiation of BMSCs, and accelerate the formation of new bone in the Angle of the mandible bone defect of rabbits.Discussion: It can be seen that 3D-printed nano-topographic surface modified porous tantalum has broad application prospects in the repair of OCMF bone defects

Diagnostic model for hepatocellular carcinoma using small extracellular vesicle-propagated miRNA signatures

BackgroundHepatocellular carcinoma (HCC) is the most common type of liver cancer. Small extracellular vesicles (sEVs) are bilayer lipid membrane vesicles containing RNA that exhibit promising diagnostic and prognostic potential as cancer biomarkers.AimsTo establish a miRNA panel from peripheral blood for use as a noninvasive biomarker for the diagnosis of HCC.MethodssEVs obtained from plasma were profiled using high-throughput sequencing. The identified differential miRNA expression patterns were subsequently validated using quantitative real-time polymerase chain reaction analysis.ResultsThe random forest method identified ten distinct miRNAs distinguishing HCC plasma from non-HCC plasma. During validation, miR-140-3p (p = 0.0001) and miR-3200-3p (p = 0.0017) exhibited significant downregulation. Enrichment analysis uncovered a notable correlation between the target genes of these miRNAs and cancer development. Utilizing logistic regression, we developed a diagnostic model incorporating these validated miRNAs. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.951, with a sensitivity of 90.1% and specificity of 87.8%.ConclusionThese aberrantly expressed miRNAs delivered by sEVs potentially contribute to HCC pathology and may serve as diagnostic biomarkers for HCC

Delivery of Protein Kinase A by CRISPRMAX and Its Effects on Breast Cancer Stem-Like Properties

Protein kinase A (PKA) activation has recently been reported to inhibit epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) ability, which is considered to be responsible for chemoresistance and tumor recurrence in patients. While current studies mainly focus on gene manipulation of the EMT process, the direct delivery of PKA enzymes to cancer cells has never been investigated. Here, we utilize the commercial Lipofectamine CRISPRMAX reagent to directly deliver PKAs to breast cancer cells and evaluate its effects on EMT regulation. We optimized the delivery parameters with fluorescent-labeled bovine serum albumin, and successfully delivered fluorescent PKAs through CRISPRMAX into breast cancer cells. Then, we evaluated the biological effects by immunofluorescence, flow cytometry, mammosphere assay, and chemoresistance assay. Our data showed the expression of EMT-related markers, alpha-smooth muscle actin and N-cadherin, was downregulated after CRISPRMAX-PKA treatment. Although the CD44(+)/CD24(-) population did not change considerably, the size of mammospheres significantly decreased. In paclitaxel and doxorubicin chemoresistance assays, we noticed PKA delivery significantly inhibited paclitaxel resistance rather than doxorubicin resistance. Taken together, these results suggest our direct enzyme delivery can be a potential strategy for inhibiting EMT/CSC-associated traits, providing a safer approach and having more clinical translational efficacy than gene manipulation. This strategy will also facilitate the direct testing of other target enzymes/proteins on their biological functions