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The wavelengths and transition rates of W40+-W42+ ions within the range of 40–140 Å, have been calculated using the Flexible Atomic Code of the Dirac-Fock-Slater method with a central potential. We investigated the charge state distribution of W38+-W45+ ions at different temperatures by constructing an appropriate rate equation and demonstrate the importance of the dielectronic recombination process. Additionally, we simulated the emission spectra of W40+-W42+ ions in a Tokamak plasma environment using collisional-radiative modeling. Our findings demonstrate strong agreement with experimental results and other related theoretical investigations. Finally, we propose certain pairs of transition lines as diagnostic tools for plasma temperature and density, leveraging the correlation between line intensity ratio and electron temperature and density. [ABSTRACT FROM AUTHOR]

The excitation energies of the Be-like ions (4 ≤ Z ≤ 74) doubly excited state 1 s 2 2 p 2 and doubly core-excited state 2 s 2 p 3 are calculated using the multi-configuration Dirac–Hartree–Fock method. The contributions of relativistic effects, Breit interaction, and QED effects to the excitation energies are analyzed and discussed in detail. A reasonable electron correlation model has been constructed using the active set method. The electron correlation and the finite size of the atomic nucleus correction have also been appropriately considered. The calculated results agree with the available theoretical and experimental data. It is found that the contribution of relativistic effects, Breit interaction, and QED effects to the excitation energy becomes significant with increasing Z. The contribution of the relativistic effects reaches about 8.5% at Z=74. The 3 P 0 level of the doubly excited state 1 s 2 2 p 2 is sensitive to the Breit interaction and the QED effects, but these two contributions cancel each other out. For the doubly core-excited state 2 s 2 p 3 , the Breit interaction and the QED effects are almost equally important, and their maximum contribution is about 0.5%. These results are expected to help future experimental and theoretical work. [ABSTRACT FROM AUTHOR]

Aims: This review aimed to assess whether oral iron supplementation in a chronic heart failure (HF) population with iron deficiency (ID) or mild anaemia is safe and effective according to evidence‐based medicine. Methods: We retrieved 1803 records from the PubMed, Embase, and the Cochrane Library databases from 1 January 1991 to 15 September 2021. The clinical outcome of oral iron supplementation for ID anaemia in patients with HF was the primary endpoint. The primary safety measures included adverse events and all‐cause mortality, and efficacy measures included transferrin saturation (Tsat), ferritin levels, and the 6‐min walk test (6MWT). The rate ratio (RR) was used to pool the efficacy measures. Results: Five randomized controlled trials that compared oral iron treatment for patients with the placebo group and included a combined total of 590 participants were analysed. No significant difference was found in all‐cause death between oral iron treatment and placebo groups (RR = 0.77; 95% confidence intervals (CI), 0.46–1.29, Z = 0.98; P = 0.33). However, adverse events were not significantly higher in the iron treatment group (RR = 0.83; 95% CI, 0.60–1.16, Z = 1.07; P = 0.28). In addition, ferritin levels and Tsat were slightly increased after iron complex administration in patients with HF but were not statistically significant (ferritin: mean difference [MD] = 2.70, 95% CI, –2.41 to 7.81, Z = 1.04; P = 0.30; Tsat: MD = 27.42, 95% CI, –4.93 to 59.78, Z = 1.66; P = 0.10). No significant difference was found in exercise capacity, as indicated by the 6MWT results (MD = 59.60, 95% CI, –17.89 to 137.08, Z = 1.51; P = 0.13). We also analysed two non‐randomized controlled trials with follow‐up results showing that oral iron supplementation increased serum iron levels (MD = 28.87, 95% CI, 1.62–56.12, Z = 2.08; P = 0.04). Conclusions: Based on the current findings, oral iron supplementation can increase serum iron levels in patients with HF and ID or mild anaemia but does not improve Tsat and 6MWT. In addition, oral iron supplementation is relatively safe. [ABSTRACT FROM AUTHOR]

Mechanistic target of rapamycin (MTOR) plays a critical role in the regulation of cell growth and in the response to energy state changes. Drugs inhibiting MTOR are increasingly used in antineoplastic therapies. Myocardial MTOR activity changes during hypertrophy and heart failure (HF). However, whether MTOR exerts a positive or a negative effect on myocardial function remains to be fully elucidated. Here, we show that ablation of Mtor in the adult mouse myocardium results in a fatal, dilated cardiomyopathy that is characterized by apoptosis, autophagy, altered mitochondrial structure, and accumulation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). 4E-BP1 is an MTOR-containing multi-protein complex-1 (MTORC1) substrate that inhibits translation initiation. When subjected to pressure overload, Mtor-ablated mice demonstrated an impaired hypertrophic response and accelerated HF progression. When the gene encoding 4E-BP1 was ablated together with Mtor, marked improvements were observed in apoptosis, heart function, and survival. Our results demonstrate a role for the MTORC1 signaling network in the myocardial response to stress. In particular, they highlight the role of 4E-BP1 in regulating cardiomyocyte viability and in HF. Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF., Introduction Mechanistic target of rapamycin (MTOR) is a key regulator of protein synthesis in the cardiomyocyte (1, 2). Increased protein synthesis underpins hypertrophic growth, a salient feature of the heart [...]

The mass- and field-shift parameters of the two 2s 2S1/2 → 2p 2P1/2,3/2 transitions in the Li-like Ca ions are calculated by using multi-configuration Dirac–Hartree–Fock (MCDHF) and the relativistic configuration interaction (RCI) methods with the inclusion of the transverse photon (Breit) interaction, vacuum polarization and self-energy corrections. In addition, the mass shift and field shift of these two transitions are calculated, where the field shift is calculated by using the evaluated value δ〈 r2〉 obtained by [Atomic Data and Nuclear Data Tables 99 69 (2013)]. It is found that the mass shift of Li-like Ca ions is greater than the field shift. [ABSTRACT FROM AUTHOR]

K‐shell dielectronic, trielectronic, and quadruelectronic recombination and polarization of X‐ray emission have been studied for the highly charged Si9+ ions in the initial ground state 2P1/2 and the metastable state 2P3/2 using the Flexible Atomic Code. It is found that the resonant recombination cross section from the long‐lived metastable state is comparable in magnitude with that of the ground state, so it is important for plasma diagnostics. For Si9+(2P1/2), trielectronic recombination contributions of nearly 25% to the total resonant recombination strength are predicted, which is less than previous calculations. We compare the degree of linear polarization for the eleven dominant resonant recombination satellite lines from the initial parent Si9+(2P1/2) and Si9+(2P3/2) ions. For the same X‐ray lines, large variations of polarization are found between 2P1/2 and 2P3/2, which can be employed to diagnose formation mechanisms of intermediate resonance states and corresponding X‐ray lines. [ABSTRACT FROM AUTHOR]

Phospholipase A2s (PLA2) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA2s, and was recently repurposed to a broad-spectrum inhibitor of PLA2 in snake venom. To evaluate the protective abilities of varespladib to hemorrhage, myonecrosis, and systemic toxicities that are inflicted by different crude snake venoms, subcutaneous ecchymosis, muscle damage, and biochemical variation in serum enzymes derived from the envenomed mice were determined, respectively. Varespladib treatment showed a significant inhibitory effect to snake venom PLA2, which was estimated by IC50 in vitro and ED50 in vivo. In animal models, the severely hemorrhagic toxicity of D. acutus and A. halys venom was almost fully inhibited after administration of varespladib. Moreover, signs of edema in gastrocnemius muscle were remarkably attenuated by administration of varespladib, with a reduced loss of myonecrosis and desmin. Serum levels of creatine kinase, lactate dehydrogenase isoenzyme 1, aspartate transaminase, and alanine transaminase were down-regulated after treatment with varespladib, which indicated the protection to viscera injury. In conclusion, varespladib may be a potential first-line drug candidate in snakebite envenomation first aid or clinical therapy. [ABSTRACT FROM AUTHOR]

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Coumarin derivatives are highly valuable compounds in drug discovery. Herein, we have developed two new coupling reactions that involve coumarins and either aldehydes or di- tert-butyl peroxide (DTBP) in the presence of inexpensive copper or iron catalysts. Both of these reactions proceed through a C(sp2)-H functionalization process to regioselectivity generate keto- or methyl-substituted coumarin derivatives in moderate to good yields These coupling reactions will enrich current coumarin chemistry. [ABSTRACT FROM AUTHOR]

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. Reference 1 Wang Y., Zhang J., Zhang D., Xiao H., Xiong S., Huang C. Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. The authors would like to correct an error in the original publication [[1]]. [Extracted from the article]

An efficient synthetic route toward the highly congested [5-6-7] tricyclic core of calyciphylline A-type alkaloids has been developed. This approach features a highly efficient intramolecular Diels-Alder cycloaddition to establish the aza-five-membered C ring as well as the C1 all-carbon quaternary center, and a subsequent cyclopropanation together with a ring-expansion reaction of the resulted adduct to construct the seven-membered D ring. [ABSTRACT FROM AUTHOR]

In order to get a better understanding of protein association during Solanum tuberosum (cv. Sarpo Mira)–Phytophthora infestans incompatible interaction, we investigated the proteome dynamics of cv. Sarpo Mira, after foliar application of zoospore suspension from P. infestans isolate, at three key time-points: zero hours post inoculation (hpi) (Control), 48 hpi (EI), and 120 hpi (LI); divided into early and late disease stages by the tandem mass tagging (TMT) method. A total of 1229 differentially-expressed proteins (DEPs) were identified in cv. Sarpo Mira in a pairwise comparison of the two disease stages, including commonly shared DEPs, specific DEPs in early and late disease stages, respectively. Over 80% of the changes in protein abundance were up-regulated in the early stages of infection, whereas more DEPs (61%) were down-regulated in the later disease stage. Expression patterns, functional category, and enrichment tests highlighted significant coordination and enrichment of cell wall-associated defense response proteins during the early stage of infection. The late stage was characterized by a cellular protein modification process, membrane protein complex formation, and cell death induction. These results, together with phenotypic observations, provide further insight into the molecular mechanism of P. infestans resistance in potatos. [ABSTRACT FROM AUTHOR]

Snake venom is a complex cocktail of toxins which induces a series of clinical and pathophysiological manifestations in victims, including severe local tissue damage and systemic alterations. Deinagkistrodon acutus (D. acutus) ranks among the “big four” life-threatening venomous species in China, whose venom possesses strong myotoxicity and hematotoxicity that often lead to permanent disability or muscle atrophy. Varespladib, an inhibitor of mammalian phospholipase A2 (PLA2), has been recently reproposed as an effective antidote against snakebite envenomation. The present study aimed at evaluating the protective role of varespladib on muscle regeneration in envenomed mice. Mice were grouped and subjected to inoculation with D. acutus venom or a mixture of venom and varespladib or control vehicle in the gastrocnemius muscle. Local injuries including hemorrhage, myonecrosis, ulceration, and systemic damages including general dysfunction, visceral failure, and inflammatory responses were observed at 1, 3, 7, 14, and 21 days. The results indicated that most of the muscle myonecrosis and hemorrhage were alleviated by varespladib. Besides, the pretreated mice recovered rapidly with lesser atrophy and muscle fibrosis. In conclusion, the findings of the present study suggested that varespladib is an effective antidote that could neutralize D. acutus venom and allow for earlier and improved rehabilitation outcome. [ABSTRACT FROM AUTHOR]

Mechanistic target of rapamycin (MTOR) plays a critical role in the regulation of cell growth and in the response to energy state changes. Drugs inhibiting MTOR are increasingly used in antineoplastic therapies. Myocardial MTOR activity changes during hypertrophy and heart failure (HF). However, whether MTOR exerts a positive or a negative effect on myocardial function remains to be fully elucidated. Here, we show that ablation of Mtor in the adult mouse myocardium results in a fatal, dilated cardiomyopathy that is characterized by apoptosis, autophagy, altered mitochondrial structure, and accumulation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). 4E-BP1 is an MTOR-containing multiprotein complex-1 (MTORC1) substrate that inhibits translation initiation. When subjected to pressure overload, Mtor-ablated mice demonstrated an impaired hypertrophic response and accelerated HF progression. When the gene encoding 4E-BP1 was ablated together with Mtor, marked improvements were observed in apoptosis, heart function, and survival. Our results demonstrate a role for the MTORC1 signaling network in the myocardial response to stress. In particular, they highlight the role of 4E-BP1 in regulating cardiomyocyte viability and in HF. Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF. [ABSTRACT FROM AUTHOR]

The non-uniformity and transient nature of laser-produced plasma are critical factors that affect the analysis of the extreme ultraviolet spectra of highly charged ions and the diagnosis of plasma states. This paper systematically investigates the characteristics of extreme ultraviolet radiation and the hydrodynamic evolution of laser-produced nickel plasmas from two perspectives: high-spatio-temporal-resolution extreme-ultraviolet spectroscopic measurement and radiation hydrodynamics simulation. The consistency between the four-band experimental spectra and their theoretically simulated spectra confirms the accuracy of the atomic structure parameters and plasma state parameters. We also analyze the significant contribution of the 3d-4f double-excited state radiation to the spectral profile and discuss the influence of the self-absorption caused by plasma opacity on the characteristics of extreme ultraviolet radiation. The findings are crucial for accurately understanding the characteristics of extreme ultraviolet radiation, the hydrodynamic evolution, and the application of medium- and high-Z laser-produced plasma as a pulsed short-wavelength light source.

We introduce a method for the analysis and simulation of transient images of laser-produced plasma (LPP) plumes. This method comprises three steps: (i) calculating the two-dimensional distribution of plasma parameters using a radiation hydrodynamics model, (ii) constructing radiation paths through ray tracing, and (iii) solving the radiation transport equation along these paths. In our simulations, we have meticulously considered factors that could influence the imaging results, including the quantum efficiency to different radiation wavelengths, the imaging lens' transmittance, the target surface's reflectivity, and the absorption, emission, and scattering quantum effect of the detector processes occurring in the plasma. We applied this method to analyze and simulate the transient images of aluminum plasma plumes in a background air environment at a pressure of 2000 Pa. The results demonstrate that our method not only produces simulated images that align with experimental results but also provides a reliable distribution of plasma state parameters and clearly identifies the ion species radiating in different bands. Given its capability in transient image reconstruction and its adaptability as a tool for spectral simulation and analysis of LPPs, we believe this method holds significant potential for spectral diagnostics in fields such as laser-induced breakdown spectroscopy, extreme ultraviolet lithography sources, and high-energy-density physics, among others.

Background: The purpose of this study was to evaluate the effectiveness of His-Purkinje system pacing (HPSP) in the management of patients with pace-induced cardiomyopathy (PICM)., Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched comprehensively to collect related studies published from the inception of databases to June 1, 2022. R 4.04 software, including the Metafor package, matrix package, and the Meta package, was utilized to conduct the singe-arm meta-analysis. The methodology index for non-randomized studies (MINORS) was used to assess the methodological quality of the included studies., Results: A total of seven studies were included, involving 164 PICM patients. The meta-analysis showed that HPSP ameliorated the left ventricular ejection fraction (LVEF) by 13.41% (95% CI [11.21-15.61]), improved the New York Heart Association (NYHA) classification by 1.02 (95% CI [-1.41 to -0.63]), and shortened the QRS duration (QRSd) by 60.85 ms (95% CI [-63.94 to -57.75]), resulting in improved cardiac functions in PICM patients. Besides, HPSP reversed the ventricular remodeling, with a 32.46 ml (95% CI [-53.18 to -11.75]) decrease in left ventricular end systolic volume (LVESV) and a 5.93 mm (95% CI [-7.68 to -4.19]) decrease in left ventricular end-diastolic dimension (LVEDD). HPSP also showed stable electrical parameters of pacemakers, with a 0.07 V (95% CI [0.01-0.13]) increase in pacing threshold, a 0.02 mV (95% CI [-0.85 to 0.90]) increase in sensed R-wave amplitude, and a 31.12 Ω reduction in impedance (95% CI [-69.62 to 7.39]). Compared with LBBP, HBP improved LVEF by 13.28% (95% CI [-11.64 to 14.92]) vs 14.43% (95% CI [-13.01 to 15.85]), ameliorated NHYA classification by 1.18 (95% CI [-1.97 to -0.39]) vs 0.95 (95% CI [-1.33 to -0.58]), shortened QRSd by 63.16 ms (95% CI [-67.00 to -59.32]) vs 57.98 ms (95% CI [-62.52 to -53.25]), and decreased LVEDD by 4.12 mm (95% CI [-5.79 to -2.45]) vs 6.26 mm (95% CI [-62.52 to -53.25]). The electrical parameters of the pacemaker were stable in both groups., Conclusions: This meta-analysis showed that HPSP could significantly improve cardiac function, promote reverse remodeling, and provide stable electrical parameters of pacemakers for PICM patients., Competing Interests: The authors declare that they have no competing interests., (© 2023 Tang et al.)

We developed a post-processing optical imaging model based on two-dimensional axisymmetric radiation hydrodynamics. Simulation and program benchmarks were performed using laser-produced Al plasma optical images obtained via transient imaging. The emission profiles of a laser-produced Al plasma plume in air at atmospheric pressure were reproduced, and the influence of plasma state parameters on radiation characteristics were clarified. In this model, the radiation transport equation is solved on the real optical path, which is mainly used to study the radiation of luminescent particles during plasma expansion. The model outputs consist of the electron temperature, particle density, charge distribution, absorption coefficient, and corresponding spatio-temporal evolution of the optical radiation profile. The model helps with understanding element detection and quantitative analysis of laser-induced breakdown spectroscopy.

Conversion of astroglia into functional neurons has been considered a promising therapeutic strategy for neurodegenerative diseases. Recent studies reported that downregulation of the RNA binding protein, polypyrimidine tract-binding protein 1 (PTBP1), converts astrocytes into neurons in situ in multiple mouse brain regions, consequently improving pathologic phenotypes associated with Parkinson's disease, RGC loss, and aging. Here, we demonstrate that PTBP1 downregulation using an astrocyte-specific AAV-mediated shRNA system fails to convert hippocampal astrocytes into neurons in both male and female wild-type (WT) and β-amyloid (5×FAD) and tau (PS19) Alzheimer's disease (AD) mouse models and fails to reverse synaptic/cognitive deficits and AD-associated pathology in male mice. Similarly, PTBP1 downregulation cannot convert astrocytes into neurons in the striatum and substantia nigra in both male and female WT mice. Together, our study suggests that cell fate conversion strategy for neurodegenerative disease therapy through manipulating one single gene, such as PTBP1, warrants more rigorous scrutiny. SIGNIFICANCE STATEMENT Our results do not support some of the recent extraordinary and revolutionary claims that resident astrocytes can be directly and efficiently converted into neurons. Our study is critical for the field of neural regeneration and degeneration. In addition, our study is financially important because it may prevent other researchers/organizations from wasting a vast amount of time and resources on relevant investigations., (Copyright © 2022 the authors.)

An efficient synthetic route toward the highly congested [5-6-7] tricyclic core of calyciphylline A-type alkaloids has been developed. This approach features a highly efficient intramolecular Diels-Alder cycloaddition to establish the aza-five-membered C ring as well as the C1 all-carbon quaternary center, and a subsequent cyclopropanation together with a ring-expansion reaction of the resulted adduct to construct the seven-membered D ring., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Trifolium pratense, a widespread legume forage plant, is reported to exhibit phytotoxic activity on other plants, but the active metabolites have not been clarified so far. A bioassay-guided fractionation of the root extracts led to the isolation of five isoflavonoids, which were elucidated by spectroscopic analysis. All of the purified compounds observably showed phytotoxic activities against Arabidopsis thaliana . Moreover, the inhibitory effects were concentration-dependent. The furan ring linked at C-4 and C-2' positions by an oxygen atom and a 1,3-dioxolane at C-4' and C-5' positions are considered to be critical factors for the phytotoxic activity. The concentrations of (6aR,11aR)-maackiain and (6aR,11aR)-trifolirhizin, concluded to be allelochemicals from soil around plants of T. pratense, were determined by HPLC and LC-MS to be 4.12 and 2.37 μg/g, respectively. These allelochemicals, which showed remarkable activities against the weed Poa annua may play an important role in assisting the widespread occurrence of T. pratense in nature.

AKT activation requires phosphorylation of the activation loop (T308) by 3-phosphoinositide-dependent protein kinase 1 (PDK1) and the hydrophobic motif (S473) by the mammalian target of rapamycin complex 2 (mTORC2). We recently observed that phosphorylation of the AKT hydrophobic motif was dramatically elevated, rather than decreased, in mTOR knockout heart tissues, indicating the existence of other kinase(s) contributing to AKT phosphorylation. Here we show that the atypical IκB kinase ε and TANK-binding kinase 1 (IKKε/TBK1) phosphorylate AKT on both the hydrophobic motif and the activation loop in a manner dependent on PI3K signaling. This dual phosphorylation results in a robust AKT activation in vitro. Consistently, we found that growth factors can induce AKT (S473) phosphorylation in Rictor(-/-) cells, and this effect is insensitive to mTOR inhibitor Torin1. In IKKε/TBK1 double-knockout cells, AKT activation by growth factors is compromised. We also observed that TBK1 expression is elevated in the mTOR knockout heart tissues, and that TBK1 is required for Ras-induced mouse embryonic fibroblast transformation. Our observations suggest a physiological function of IKKε/TBK1 in AKT regulation and a possible mechanism of IKKε/TBK1 in oncogenesis by activating AKT.