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This paper investigates the potential regulatory frameworks applicable to marine bioprospecting in the Southern Ocean and considers the activity could potentially fall under the purview of both the Antarctic Treaty System and the Biodiversity Beyond National Jurisdiction Agreement. Through a comparative analysis, this paper discerns the overlap of application and divergence in rules between the two regulatory frameworks, particularly concerning the specific provisions for regulating marine bioprospecting. This includes dissecting differences in the rules regulating the procedures for access to marine genetic resources and the associated benefit-sharing mechanisms. By synthesizing the SWOT analysis and strategic analysis, this paper identifies the internal and external factors influencing the application of the BBNJ Agreement to bioprospecting regulation within the Southern Ocean. It concludes that, due to the priority application of ATS and the region's unique geopolitical context, the BBNJ Agreement may encounter challenges in the direct implementation and governance of marine bioprospecting. The principle of not undermining should be observed to harmonize application with ATS. Meanwhile, the BBNJ Agreement may contribute to a self-revolution of the ATS in regulating marine bioprospecting, particularly in the aspect of mechanisms for equitable benefit-sharing. [ABSTRACT FROM AUTHOR]

The development of all-solid-state batteries has become an inevitable trend as safety is increasingly valued. Naturally, solid-state electrolytes(SSEs) have attracted extensive attention. The composite of superionic conductors and polymer is considered to be a material that can achieve both high energy density and safety. Nevertheless, the compatibility between the polymer and superionic conductors is poor due to the large differences in structure and electrochemistry, resulting in a high interfacial transport energy barrier of the cation. In this work, a functional Li x -CeO 2 (LCO) layer is synthesized on the surface of the superionic conductor. While broadening the cation transport path at the interface, the anion of lithium salt is successfully anchored and the concentration of lithium-ion is increased. In addition, the structural compatibility and adhesion between polymer and superionic conductors are improve. Compared with the pristine electrolyte, the ionic conductivity and the lithium-ion transference number (t Li+) of LLZTO@2%LCO are as high as 2.325 × 10−3 S cm−1(pristine sample is only 7.109 × 10−5 S cm−1) and 0.44 (pristine sample is only 0.27)respectively. At 2C, the discharge specific capacity of LiFePO 4 (LFP)|LLZTO@2%LCO-CSE|Li can reach 134.8mAh g−1. The outstanding performance of the composite electrolyte is attributed to the interface functionalized Li x -CeO 2 compound coating. Therefore, polymer/ceramic interface engineering to promote the interaction between the two components should be one of the directions of future research. [ABSTRACT FROM AUTHOR]

Abstract: An ab initio potential energy surface (PES) for the ground state (1) of the chemical reaction → ArH+ +H has been constructed from a set of accurate ab initio data, which we have computed using the coupled-cluster theory including all single and double excitations plus perturbative corrections for the triples UCCSD(T) with a large orbital basis set of aug-cc-pV5Z. The new PES has a root-mean-square (rms) error of 0.5341kcal/mol. The total integral reaction cross-sections have been calculated at three collision energies by means of the quasi-classical trajectory (QCT) calculation based on the new PES and compared with previous TSH results. [Copyright &y& Elsevier]

Poly(ethylene oxide) based polymer electrolytes(PEO-SPEs) suffer from a narrow electrochemical window and deliver poor electrochemical performance when coupling with 4.2 V cathode. This severely limits the scope of its application. Here, a combination of physical stirring and electrochemistry is used to form an ultrathin and uniform cladding layer on the LiCoO 2 particles. The results show that in addition to the decomposition of LiPO 2 F 2 during the charge/discharge cycling, decomposition reactions occur during the stirring and drying process by X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM). This novel method effectively improves the electrochemical performance of 4.2 V PEO based solid-state lithium batteries. In particular, the cell shows excellent and stable electrochemical performance, exhibiting a discharge capacity of 112.0 mAh g−1 after 200 cycles, a capacity retention rate of 79.4% and a capacity decay rate of approximately 0.1% per cycle when the surface of LiCoO 2 is coated with 2 wt% LiPO 2 F 2. In comparison, the discharge capacity of the unmodified LiCoO 2 cathode is found to be only 75.6 mAh g−1 after 100 cycles, with a poor capacity retention rate of 56.8%. Based on the basis of the above research, a new process was explored and also shows excellent interfacial stability by dispersing LiPO 2 F 2 directly inside the binder which with a discharge capacity of 109.2 mAh g−1 and a capacity retention rate of 84.5% after 145 cycles. This novel approach opens up a new pathway for solving the problem of interfacial stability between PEO based polymer electrolytes and high-voltage cathode. [ABSTRACT FROM AUTHOR]

[Display omitted] Phenotypic transition of vascular smooth muscle cells (VSMCs) is an early event in the onset and progression of several cardiovascular diseases. As an important mediator of the renin-angiotensin system (RAS), activation of the angiotensin II type 1 receptor (AT1R) induces phenotypic transition of VSMCs. AT1R autoantibodies (AT1-AAs), which are agonistic autoantibodies of AT1R, have been detected in the sera of patients with a variety of cardiovascular diseases associated with phenotypic transition. However, the effect of AT1-AA on phenotypic transition is currently unknown. In this study, AT1-AA-positive rat model was established by active immunization to detect markers of VSMCs phenotypic transition. The results showed that AT1-AA-positive rats showed phenotypic transition of VSMCs, which was evidenced by the decrease of contractile markers, while the increase of synthetic markers in the thoracic aorta. However, in AT1-AA-positive AT1R knockout rats, the phenotypic transition-related proteins were not altered. In vitro , after stimulating human aortic smooth muscle cells with AT1-AA for 48 h, 2′-5′ oligoadenylate synthase 2 (OAS2) was identified as the key differentially expressed gene by RNA sequencing and bioinformatics analysis. Furthermore, high expression of OAS2 was found in aorta of AT1-AA-positive rats; knockdown of OAS2 by siRNA can reverse the phenotypic transition of VSMCs induced by AT1-AA. In summary, this study suggests that AT1-AA can promote phenotypic transition of VSMCs through AT1R-OAS2 pathway, and OAS2 might serve as a potential therapeutic target to prevent pathological phenotypic transition of smooth muscle cells. [ABSTRACT FROM AUTHOR]

Sp1-CSE-H 2 S pathway plays an important role in homocysteine-metabolism, whose disorder can result in hyperhomocysteinemia. H 2 S deficiency in hyperhomocysteinemia has been reported, while the underlying mechanism and whether it in turn affects the progress of hyperhomocysteinemia are unclear. This study focused on the post-translational modification of Sp1/CSE and revealed four major findings: (1) Homocysteine-accumulation augmented CSE's nitration, inhibited its bio-activity, thus caused H 2 S deficiency. (2) H 2 S deficiency inhibited the S-sulfhydration of Sp1, down-regulated CSE and decreased H 2 S further, which in turn weakened CSE's own S-sulfhydration. (3) CSE was S-sulfhydrated at Cys84, Cys109, Cys172, Cys229, Cys252, Cys307 and Cys310, among which the S-sulfhydration of Cys172 and Cys310 didn't affect its enzymatic activity, while the S-sulfhydration of Cys84, Cys109, Cys229, Cys252 and Cys307 was necessary for its bio-activity. (4) H 2 S deficiency trapped homocysteine-metabolism into a vicious cycle, which could be broken by either blocking nitration or restoring S-sulfhydration. This study detected a new mechanism that caused severe hyperhomocysteinemia, thereby provided new therapeutic strategies for hyperhomocysteinemia. Image 1 • Hcy augmented the nitration of CSE, blunted its bio-activity and caused H 2 S deficiency. • Deficiency of Sp1's S-sulfhydration down-regulated CSE, lowered H 2 S level further, which weakened CSE's S-sulfhydration. • CSE was S-sulfhydrated at Cys84, Cys109, Cys172, Cys229, Cys252, Cys307 and Cys310 under physiological conditions. • H 2 S deficiency trapped HHcy into a vicious cycle, blocking nitration or restoring S-sulfhydration could break this cycle. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) seriously influences human health, and there is no effective treatment to prevent or cure AD. Recent studies have shown that angiotensin II type 1 receptor (AT1R) blockers significantly reduce the prevalence of AD, while the precise role and mechanism of AT1R in AD remain obscure. In this study, for the first time, we identified that astrocytic but not neuronal AT1R levels were significantly increased in AD model rats and found that astrocyte-specific knockout of AT1R significantly ameliorated amyloid β (Aβ)-induced cognitive deficits and synaptotoxicity. Pretreating astrocytes with an AT1R blocker also alleviated Aβ-induced synaptotoxicity in the coculture system of hippocampal neurons and astrocytes. Moreover, AT1R could directly bind to Aβ 1–42 and activate the astrocytic β-arrestin2 pathway in a biased manner, and biased inhibition of the astrocytic AT1R/β-arrestin2 pathway relieved Aβ-induced neurotoxicity. Furthermore, we demonstrated that astrocytic AT1R/β-arrestin2 pathway-mediated synaptotoxicity was associated with the aggregation of autophagosomes, which triggered the disordered degradation of Aβ. Our findings reveal a novel molecular mechanism of astrocytic AT1R in Aβ-induced neurodegeneration and might contribute to establishing new targets for AD prevention and therapy. [Display omitted] • Astrocytic AT1R levels were upregulated in the hippocampus of AD model animals. • Astrocytic AT1R deficiency ameliorated Aβ-induced cognitive deficits and synaptotoxicity. • AT1R directly bound to oAβ 1–42 and activated the astrocytic AT1R/β-arrestin2 pathway in a biased manner. • Biased inhibition of the astrocytic AT1R/β-arrestin2 pathway ameliorated Aβ-induced cognitive deficits and synaptotoxicity. • Astrocytic AT1R/β-arrestin2 pathway-mediated synaptotoxicity was associated with aggregation of autophagosomes. [ABSTRACT FROM AUTHOR]

Abstract Phytophthora infestans is one of the most notorious pathogen among Phytophthora species causing potato late blight disease. Stable and long-term preservation of this pathogen is essential for biological research and fungicide screening. The aim of this study was to find a suitable long-term preservation method for P. infestans. We adjusted the storage temperature, made a slight modification to the rye seed method, and compared the influence of four preservation methods (the mineral oil method, the sterile water method, the rye seed method, and the modified rye seed method) on survival, growth and virulence of four isolates of P. infestans. The results showed that all four methods maintained high viability of the tested P. infestans isolates, but the two rye seed methods were the best ways to maintain 100% viability of the P. infestans isolates without contamination. The four preservation methods did not significantly influence growth or morphological characteristics of the P. infestans isolates. The impacts of the four methods on the virulence of the four P. infestans isolates were isolate-specific. For isolates YF3 and 64093, all four methods were suitable for maintaining their virulence. Whilst for isolate HQK8–3, the rye seed and sterile water methods were more suitable to maintain its virulence than the other two methods. For isolate 32835, storage under mineral oil was the best method for maintaining its virulence. In view of these results, it is recommended P. infestans should be stored by several different storage methods to ensure the safety and stability of the isolates. Highlights • A stable and long-term preservation method is essential for Phytophthora infestans. • The four methods can maintain a high viability of P. infestans. • The four methods have no influence on the growth and morphology of the species. • The influence of the four methods on the pathogenicity were isolate-specific. • The isolates of P. infestans should be stored by several different storage methods. [ABSTRACT FROM AUTHOR]

The internalization of angiotensin II type 1 receptor (AT 1 R) plays an important role in maintaining cardiovascular homeostasis. Decreased receptor internalization is closely related to cardiovascular diseases induced by the abnormal activation of AT 1 R, such as hypertension. However, the mechanism behind reduced AT 1 R internalization is not fully understood. This review focuses on four parts of the receptor internalization process (the combination of agonists and receptors, receptor phosphorylation, endocytosis, and recycling) and summarizes the possible mechanisms by which AT 1 R internalization is reduced based on these four parts of the process. (1) The agonist has a large molecular weight or a stronger ability to hydrolyze phosphatidylinositol 4,5-bisphosphate (PtdIns (4,5) P 2 ), which can increase the consumption of PtdIns (4,5) P 2 . (2) AT 1 R phosphorylation is weakened because of an abnormal function of phosphorylated kinase or changes in phospho-barcoding and GPCR–β-arrestin complex conformation. (3) The abnormal formation of vesicles or AT 1 R heterodimers with fewer endocytic receptors results in less AT 1 R endocytosis. (4) The enhanced activity and upregulated expression of small GTP-binding protein 4 (Rab4) and 11 (Rab11), which regulate receptor recycling, and phosphatidylinositol 3-kinase increase AT 1 R recycling. In addition, lower expression of AT 1 R-associated protein (ATRAP) or higher expression of AT 1 R-associated protein 1 (ARAP1) can reduce receptor internalization. [ABSTRACT FROM AUTHOR]

Deficiency of cystathionine β-synthase (CBS) activity is the most common cause of increased homocysteine (Hcy). However, until now the underlying mechanisms why CBS activity decreased still remain unresolved. The goal of this study was to explore the contribution of nitrative stress to deficiency of CBS activity, and further identify the possible nitration sites of CBS protein. Results showed that in elderly people, there was an increased nitrative stress level, which was relative to elevated Hcy level. In natural aging rats and diet-induced hyperhomocysteinemia (HHcy) rats, the levels of Hcy and nitrative stress were both elevated, and interestingly, pretreatment with peroxynitrite (ONOO - ) scavenger FeTMPyP ameliorated the elevation of Hcy as well as nitrative stress. Further experiments showed the reduction of CBS bioactivity and elevation of CBS nitration in two rats models were both reversed by FeTMPyP pretreatment. In vitro, replacement of tyrosine (Tyr, Y) residue (Tyr 163 , Tyr 223 , Tyr 381 , Tyr 518 ) in CBS with alanine (Ala, A) abolished the Hcy-mediated CBS inactivation. These results highlighted that deficiency of CBS activity was correlated with the nitration of CBS at Tyr 163 , Tyr 223 , Tyr 381 and Tyr 518 , which may play a mutual role in the progression of HHcy. This discovery may shed a novel light on the pathogenesis of HHcy and provide a possible gene therapy target to HHcy. [ABSTRACT FROM AUTHOR]

Objectives The incidence of arrhythmia is associated with autoantibodies against the second extracellular loop of β 1 -adrenergic receptor (β 1 -AAbs). The current study was designed to determine the mechanisms by which arrhythmia experimentally might be induced by β 1 -AAbs. Methods Blood samples were collected from patients with varied arrhythmias or coronary heart disease (CHD) and healthy subjects. The titer of β 1 -AAbs was assessed. Passive immunization rat models with β 1 -AAbs were established to determine whether β 1 -AAbs induced arrhythmia. Conventional intracellular microelectrode technique and whole cell patch clamp were employed to record action potential duration (APD), resting potential (RP), L-type calcium current ( I Ca-L ), sodium–calcium exchange current (INCX), transient outward potassium current ( I to ), inward rectifier potassium current ( I k1 ) and delayed rectifier potassium current ( I k ). Results High levels of β 1 -AAbs were found in the sera of heart disease patients, especially in ventricular arrhythmia (VA). Transfusion with β 1 -AAbs could induce arrhythmias in normal rats in vivo. β 1 -AAbs purified from the sera of active immunized rats induced triggered activity (TA), delayed after depolarization (DAD), and prolonged APD in the papillary muscles of rats. β 1 -AAbs prolonged QT interval, increased I Ca-L and decreased I K1 , I to and I Na–Ca in rat ventricular myocytes in vitro. All these effects can be inhibited by β 1 -AR blocker metoprolol. Conclusions These results demonstrate for the first time that β 1 -AAbs could directly induce ventricular arrhythmia by prolonging QT interval. [ABSTRACT FROM AUTHOR]

Phytophthora infestans is the most devastating pathogen of potato. For the biology study of P. infestans at the molecular level, one of the difficulties is the technique for the genetic transformation. In this study, the straightforward electro-transformation system was established for P. infestans with a green fluorescent protein expression vector and compared with the improved PEG/CaCl 2 mediated protoplast transformation system. The results showed that the straightforward electro-transformation could work in P. infestans and 32 positive transformants were obtained per about 1.10 × 10 6 zoospores. The transformants per μg of vector DNA were 1.08. The transformation efficiency of the straightforward electro-transformation was approximately 2 times higher than that of the improved PEG/CaCl 2 mediated protoplast transformation (17 positive transformants per about 1.05 × 10 6 protoplasts, 0.58 transformants per μg of vector DNA) according to the reported procedures. Furthermore, compared with the improved PEG/CaCl 2 transformation, the straightforward electroporation is simpler and requires less starting materials and operating time from collecting material to obtaining the resistant transformants. Our work will lay a foundation for the biology study of P. infestans in the future. [ABSTRACT FROM AUTHOR]

Abstract: Background: β1-Adrenoceptors (β1-ARs) are the predominant receptors in regulating heart functions. β1-ARs contain 7-transmembrane domains (7TM), 3 extracellular loops and 3 intracellular loops. Among these loops, the second extracellular loop of β1-AR (β1-AR-ECII) plays an important role in the pathogenesis of heart failure. Methods: (1) Select the sera-negative rats for antibodies against β1-AR-ECII. (2) Detect the level of antibodies against β1-AR-ECII in the process of active immunization with artificial synthetic peptides according to the sequence of human β1-AR-ECII. (3) Observe its long-term role on cardiac structure and function in vivo by immunizing rats. (4) Detect the changes of T lymphocytes subsets in the process of active immunization. Results: The peptides induced the production of specific autoantibody against β1-AR-ECII. Furthermore, immunization with β1-AR-ECII peptide induced both morphological and functional alterations in the hearts of rats, which potentially results in heart failure. In addition, induction of the autoantibodies against β1-AR-ECII increased the CD4 +/CD8 + ratio in the peripheral blood of rats. Discussion: In this study, we determined the effect of anti-β1-AR-ECII autoantibody on morphological and functional cardiomyopathic alterations by immunization of rats with a synthetic peptide corresponding to the β1-AR-ECII for 18months. These results provide further evidence that autoantibody against β1-AR-ECII is involved in the pathogenesis of heart failure. But the underlying mechanisms need further study. [Copyright &y& Elsevier]

Blood glucose is of great importance to development and metabolic homeostasis in fetuses. Stimulation of harmful factors during gestation induces pathoglycemia. Angiotensin II type 1 receptor autoantibody (AT1-AA), a newly discovered gestational harmful factor, has been shown to induce intrauterine growth restriction in fetuses and glucose disorders in adults. However, whether and how AT1-AA influences the blood glucose level of fetuses during gestation is not yet clear. The purpose of the current study was to observe the fetal blood glucose level of AT1-AA-positive pregnant rats during late pregnancy and to determine the roles that hepatic glucose transporters play in this process. We established AT1-AA-positive pregnant rats by injecting AT1-AA into the caudal veins of rats in the 2nd trimester of gestation. Although the fetal blood glucose level in the 3rd trimester of gestation decreased, hepatic glucose uptake increased detected. Through separating membrane and cytosolic proteins, we demonstrated that both the expression and membrane transport ratio of glucose transporter 1 (GLUT1), which is responsible for glucose transport in fetal hepatocytes, were upregulated, accompanied by increased expression of N-glycosyltransferase STT3A, which contributes to the N-glycosylation of GLUT1. In vitro , we identified that AT1-AA increased glucose uptake, the expression and membrane transport ratio of GLUT1 and the expression of STT3A in HepG2 cell lines via separating membrane and cytosolic proteins and immunofluorescence, resulting in the decreased glucose content in the medium. The GLUT1 inhibitor WZB117 reversed the decreases in glucose content in the medium, the increases in glucose uptake, the increases in the expression and membrane transport ratio of GLUT1 caused by AT1-AA. The N-glycosyltransferase inhibitor NGI as well as si-STT3A reversed the AT1-AA-induced upregulation of the STT3A-GLUT1-glucose uptake effect. This study demonstrates that AT1-AA lowers the blood glucose level of fetuses via the STT3A-GLUT1-glucose uptake axis in liver. • Angiotensin II type 1 receptor autoantibody (AT1-AA) exposure during pregnancy induced hypoglycemia in fetuses. • The hepatic glucose uptake increases in the fetuses of the AT1-AA positive pregnant rats. • The fetuses of AT1-AA-positive pregnant rats presented the increased the hepatic glucose content by promoting the STT3A-GLUT1-glucose uptake axis. [ABSTRACT FROM AUTHOR]

• Kv channel-mediated vasodilation of coronary artery was impaired in ZDF rats. • AGEs reduced Kv expression and currents in CSMCs via activating NF-κB pathway. • Blocking AGEs or NF-κB pathway improved coronary artery dilation in ZDF rats. Excessive formation of advanced glycation end products (AGEs) impairs voltage-gated potassium (Kv) channels in rat coronary artery smooth muscle cells (CSMCs), resulting in weakened Kv-mediated coronary vasodilation. We hypothesized that induction of the nuclear factor-κB (NF-κB) signaling pathway by AGEs plays a significant role in the regulation of Kv channel-mediated vasodilation in Zucker diabetic fatty (ZDF) rats. Assays of mRNA transcripts, protein expression, and intracellular localization as well as patch-clamp experiments in cultured CSMCs revealed that AGEs significantly induced activation of the NF-κB signaling pathway, reduced Kv1.2/1.5 expression, and inhibited Kv currents. In addition, silencing of the receptor for AGEs (RAGE) or p65 with siRNA and treatment with alagrebrium (ALA) or pyrrolidine dithiocarbamate (PDTC) alleviated the AGE-induced impairment of Kv channels in CSMCs. Compared with Zucker lean (ZL) rats, the amount of AGEs, RAGE protein expression, and NF-κB activity in coronary arteries were higher in ZDF rats; whereas Kv1.2/1.5 expression was significantly lower in ZDF rats. Reduced Kv1.2/1.5 expression in coronary arteries and impaired Kv-mediated coronary relaxation tested by wire myography in ZDF rats were markedly improved by treatment with aminoguanidine (AG), ALA, or PDTC. These effects were accompanied by diminished NF-κB activity, inflammation, and oxidative stress. Taken together, these results indicate that an increased interaction between AGEs and RAGE in diabetic rats leads to impaired Kv channel-mediated coronary vasodilation. Moreover, activation of the NF-κB signaling pathway and a subsequent increase of inflammation and oxidative stress may play an important role in AGE-induced impairment of coronary vasodilation in diabetes. [ABSTRACT FROM AUTHOR]