Targeting the vasopressin type-2 receptor for renal cell carcinoma therapy.

Arginine vasopressin (AVP) and its type-2 receptor (V2R) play an essential role in the regulation of salt and water homeostasis by the kidneys. V2R activation also stimulates proliferation of renal cell carcinoma (RCC) cell lines in vitro. The current studies investigated V2R expression and activity in human RCC tumors, and its role in RCC tumor growth. Examination of the cancer genome atlas (TCGA) database, and analysis of human RCC tumor tissue microarrays, cDNA arrays and tumor biopsy samples demonstrated V2R expression and activity in clear cell RCC (ccRCC). In vitro, V2R antagonists OPC31260 and Tolvaptan, or V2R gene silencing reduced wound closure and cell viability of 786-O and Caki-1 human ccRCC cell lines. Similarly in mouse xenograft models, Tolvaptan and OPC31260 decreased RCC tumor growth by reducing cell proliferation and angiogenesis, while increasing apoptosis. In contrast, the V2R agonist dDAVP significantly increased tumor growth. High intracellular cAMP levels and ERK1/2 activation were observed in human ccRCC tumors. In mouse tumors and Caki-1 cells, V2R agonists reduced cAMP and ERK1/2 activation, while dDAVP treatment had the reverse effect. V2R gene silencing in Caki-1 cells also reduced cAMP and ERK1/2 activation. These results provide novel evidence for a pathogenic role of V2R signaling in ccRCC, and suggest that inhibitors of the AVP-V2R pathway, including the FDA-approved drug Tolvaptan, could be utilized as novel ccRCC therapeutics

Multiple influence of immune cells in the bone metastatic cancer microenvironment on tumors

Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells in situ constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells, dendritic cells, and megakaryocytes, evaluating their interaction with cytotoxic T lymphocytes and contribution to bone metastasis. As important components of skeletal tissue, osteoclasts and osteoblasts derived from bone marrow stromal cells, engaging in ‘vicious cycle’ accelerate osteolytic bone metastasis. We also explain the concept tumor dormancy and investigate underlying role of immune microenvironment on it. Additionally, a thorough review of emerging treatments for bone metastatic malignancy in clinical research, especially immunotherapy, is presented, indicating current challenges and opportunities in research and development of bone metastasis therapies

Perfect state transfer on bi-Cayley graphs over abelian groups

The study of perfect state transfer on graphs has attracted a great deal of attention during the past ten years because of its applications to quantum information processing and quantum computation. Perfect state transfer is understood to be a rare phenomenon. This paper establishes necessary and sufficient conditions for a bi-Cayley graph having perfect state transfer over any given finite abelian group. As corollaries, many known and new results are obtained on Cayley graphs having perfect state transfer over abelian groups, (generalized) dihedral groups, semi-dihedral groups and generalized quaternion groups. Especially, we give an example of a connected non-normal Cayley graph over a dihedral group having perfect state transfer between two distinct vertices, which was thought impossible

Intelligent Vehicle Formation System Based on Information Interaction

Urban traffic congestion has become an increasingly serious problem, and the transportation industry is gradually becoming a high-energy-consuming industry. Intelligent Transportation System (ITSs) that integrate technologies such as electronic sensing, data transmission, and intelligent control have emerged as a new approach to fundamentally solving transportation problems. As one of the cores of intelligent transportation systems, multi-vehicle formation technology has the advantage of promoting vehicle information interaction, improving vehicle mobility, and enhancing traffic conditions. Due to the high cost and risk of conducting multi-vehicle formation experiments using real vehicles, experimenting with intelligent vehicles has become a viable option. Based on the leader–follower formation strategy, this study designed an intelligent vehicle formation system using the Arduino platform. It utilizes infrared sensors, ultrasonic sensors, and photoelectric encoders to perceive information about the vehicle fleet and the road. Information is aggregated to the master vehicle through ZigBee communication modules. The controller of the master vehicle applies a PID algorithm, combined with a differential steering model, to solve the speed instructions for each vehicle in the fleet. Motion control instructions are then transmitted to each slave vehicle through ZigBee communication modules, enabling the automatic adjustment of the fleet’s traveling speed and spacing. Additionally, a Bluetooth app has been designed for users to monitor and control the movement status of the fleet dynamically in real time. Experimental verification has shown that this research effectively improves intelligent fleets’ capabilities in environmental perception, intelligent decision-making, collaborative control, and motion execution. It also enhances road traffic efficiency and safety, providing new ideas and methods for the development of autonomous driving technology

The complete chloroplast genome sequence and phylogenetic analysis of Flaveria bidentis (L.) Kuntze, an invasive alien plant species in China

Flaveria bidentis (L.) Kuntze (Asteraceae) is one of the most hazardous invasive alien plant species and spread rapidly in China. In this study, the complete chloroplast genome of F. bidentis was sequenced using Illumina HiSeq X Ten platform. The results showed that the length of chloroplast genome of F. bidentis is 152, 230 bp, including a small single-copy region (18,362 bp), a large single-copy region (83,798 bp) and two inverted repeat regions (25,035 bp). The chloroplast genome contains 115 unique genes, including 81 protein-coding genes, four rRNA genes, and 30 tRNA genes. In total, we found 32 tandem repeats, 34 dispersed repeats and 36 SSRs in the chloroplast genome of F. bidentis. Phylogenetic analysis revealed that F. bidentis was in an independent clade and did not belong to the tribe Heliantheae Cass

Geochronology, geochemistry and Hf–Sr–Nd isotopes of the ore-bearing syenite from the Shapinggou porphyry Mo deposit, East Qinling-Dabie orogenic belt

The Shapinggou Mo deposit is located in the western Dabie mountains, the eastern part of the Qinling-Dabie molybdenum orogenic belt. Shapinggou Mo deposit is a concealed deposit with the ore body mainly hosted by explosive breccia of Gaijing and the granite porphyry as well as the syenite of Shapinggou. Geochemistry study show that the SiO2 contents of Shapinggou syenite range from 61.74 to 69.93%, and the A/CNK from 0.95 to 1.06, classified as metaluminous to weak peraluminous, belonging to alkalic to shoshonitic series. The Mo deposits in Qinling Mo belt formed in two main periods, i.e., the first period occurred in to the Early Cretaceous (145–130 Ma), the second period in the late Early Cretaceous (130–110 Ma). Most of the Mo deposits in Dabie region formed in the second period. The results of zircon U–Pb show that the age of the Shapinggou syenite is 111.3 ± 1.2 Ma, which belongs to the second period. Proterozoic-Archean inherited zircons suggest that it may include some more ancient crustal material like Kongling group. The ɛHf(t) values of Shapinggou syenite range from −15.6 to −8.0, TDM2(Hf) from 1.7 to 2.16 Ga, respectively. The ɛNd(t) values of the Shapinggou syenite range from −12.29 to −11.76, TDM2(Nd) from 1.85 to 1.89 Ga, the 87Sr/86Sr from 0.709 to 0.710, respectively. Results of zircon Hf isotope and whole rock Sr–Nd isotope of Shapinggou syenite indicate that the Mo ore-forming materials were mainly generated from old Yangtze craton, e.g., gneiss from Dabie orogeny, mixed with some juvenal mantle materials. The geodynamics of the Shapinggou Mo deposit corresponded to an extension period in Eastern China, which caused by large scale lithospheric thinning. The delamination caused asthenosphere upwelling and crust-mantle interaction, which provided the ore-forming material and heat

Glycogen synthase kinase-3 inhibition attenuates fibroblast activation and development of fibrosis following renal ischemia-reperfusion in mice

Glycogen synthase kinase-3β (GSK3β) is a serine/threonine protein kinase that plays an important role in renal tubular injury and regeneration in acute kidney injury. However, its role in the development of renal fibrosis, often a long-term consequence of acute kidney injury, is unknown. Using a mouse model of renal fibrosis induced by ischemia-reperfusion injury, we demonstrate increased GSK3β expression and activity in fibrotic kidneys, and its presence in myofibroblasts in addition to tubular epithelial cells. Pharmacological inhibition of GSK3 using TDZD-8 starting before or after ischemia-reperfusion significantly suppressed renal fibrosis by reducing the myofibroblast population, collagen-1 and fibronectin deposition, inflammatory cytokines, and macrophage infiltration. GSK3 inhibition in vivo reduced TGF-β1, SMAD3 activation and plasminogen activator inhibitor-1 levels. Consistently in vitro, TGF-β1 treatment increased GSK3β expression and GSK3 inhibition abolished TGF-β1-induced SMAD3 activation and α-smooth muscle actin (α-SMA) expression in cultured renal fibroblasts. Importantly, overexpression of constitutively active GSK3β stimulated α-SMA expression even in the absence of TGF-β1 treatment. These results suggest that TGF-β regulates GSK3β, which in turn is important for TGF-β–SMAD3 signaling and fibroblast-to-myofibroblast differentiation. Overall, these studies demonstrate that GSK3 could promote renal fibrosis by activation of TGF-β signaling and the use of GSK3 inhibitors might represent a novel therapeutic approach for progressive renal fibrosis that develops as a consequence of acute kidney injury

The complete chloroplast genome of Opisthopappus taihangensis (Ling) Shih

Opisthopappus taihangensis (Ling) Shih is a monotypic species (Anthemideae, Asteraceae) and an endemic endangered plant of China. In this study, we sequenced the complete chloroplast genome of O. taihangensis using Illumina HiSeq X Ten platform. The total length of O. taihangensis chloroplast genome is 151,089 bp, including a large single-copy region of length 82,877 bp, a small single-copy region of length 18304 bp, and a pair of 24,954-bp inverted repeat regions. The chloroplast genome of O. taihangensis has 132 genes, including 87 protein-coding, eight ribosomal RNA, and 37 transfer RNA genes. The overall GC content of the whole genome was 37.5%. The phylogenetic analysis revealed a close relationship between O. taihangensis and Chrysanthemum boreale

Specific deletion of glycogen synthase kinase-3β in the renal proximal tubule protects against acute nephrotoxic injury in mice

Renal proximal tubular damage and repair are hallmarks of acute kidney injury. As glycogen synthase kinase-3β (GSK3β) is an important cellular regulator of survival and proliferation, we determined its role during injury and recovery of proximal tubules in a mercuric chloride–induced nephrotoxic model of acute kidney injury. Renal proximal tubule–specific GSK3β knockout mice exposed to mercuric chloride had improved survival and renal function compared to wild-type mice. Apoptosis, measured by TUNEL staining, Bax activation, and caspase 3 cleavage, was reduced in the knockout mice. The restoration of renal structure, function, and cell proliferation was also accelerated in the GSK3β knockout mice. This enhanced repair, evidenced by increased Ki-67 and BRDU staining, along with increased cyclin D1 and c-myc levels, was recapitulated by treatment of wild-type mice with the small-molecule GSK3 inhibitor TDZD-8 following injury. This confirmed that hastened repair in the knockout mice was not merely due to lower initial injury levels. Thus, inhibition of GSK3β prior to nephrotoxic insult protects from renal injury. Such treatment after acute kidney injury may accelerate repair and regeneration