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Abstract A novel combined measurements techniques has been designed in this work, enabling the acquisition of laser-induced breakdown spectroscopy (LIBS) and Raman spectral signals at the same point on a sample. The application of this combined technique to the analysis of multi-layered mock-up blocks painted with orpiment and realgar pigments has yielded significant insights. By correlating variations in the emission line intensity of characteristic elements within the LIBS spectra with depth-specific Raman spectra, the number of laser pulses that penetrated the pigment layers has been accurately determined, thereby establishing a method to measure layer thickness. Finally, the technique wasto analysis the actual mural fragment from Mogao Cave 196, determining the types of pigment and the thickness of the pigment layers. Graphical Abstract

Abstract Background Lead dislodgements, tricuspid valve failure, and wound infections are prominent issues addressed by leadless pacemakers (LPM). These devises have emerged as viable alternatives to conventional transvenous pacemakers. LPMs offer minimized complications and effective pacing, particularly beneficial for elderly patients with a low body mass index (BMI) who are at heightened infection of risk. The Micra AV leadless pacemaker was released in the US in 2020, featuring a VDD pacing mode akin to conventional pacemakers. It senses atrial activity to pace ventricular beats while maintaining the natural atrioventricular activation sequence. Micra AV achieves atrioventricular synchronization through mechanical sensing principles. Ongoing research aims to assess its efficacy, implantation feasibility, and clinical safety. Case presentation An 83-year-old man with a history of syncope was the focus of this case study. An implantable cardiac monitor (ICM) recorded occasional high-degree atrioventricular block in the patient. Subsequently, the Micra AV was implanted via the left femoral vein, and its settings were adjusted in accordance with data obtained from the ICM. No significant issues regarding pacing threshold or impedance were found during the follow-up examinations post-surgery. Importantly, the patient experienced a noticeable reduction in symptoms compared to before the implantation. Discussion This case underscores the significance of ICM monitoring in elucidating cardiac events leading to syncope and guiding appropriate treatment. It also highlights the successful outcomes and reliable implantation of the Micra AV for managing high-degree atrioventricular block. This study contributes to the growing body of evidence supporting the adoption of leadless pacemakers as a viable option for patients requiring cardiac pacing, particularly those vulnerable to complications associated with traditional pacemakers. It provides real-world evidence of Micra AV’s efficacy and safety, further validating its role in clinical practice.

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.

The wavelengths and transition rates of W ^40+ -W ^42+ 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 W ^38+ -W ^45+ 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 W ^40+ -W ^42+ 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 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 Background Late blight disease (LBD) caused by the pathogen Phytophthora infestans (PI), is the most devastating disease limiting potato (Solanum tuberosum) production globally. Currently, this disease pathogen is re-emerging and appearing in new areas at a very high intensity. A better understanding of the natural defense mechanisms against PI in different potato cultivars especially at the protein level is still lacking. Therefore, to elucidate potato proteome response to PI, we investigated changes in the proteome and leaf morphology of three potato cultivars, namely; Favorita (FA), Mira (MA), and E-malingshu N0.14 (E14) infected with PI by using the iTRAQ-based quantitative proteomics analysis. Results A total of 3306 proteins were found in the three potato genotypes, and 2044 proteins were quantified. Cluster analysis revealed MA and E14 clustered together separately from FA. The protein profile and related functions revealed that the cultivars shared a typical hypersensitive response to PI, including induction of elicitors, oxidative burst, and suppression of photosynthesis in the potato leaves. Meanwhile, MA and E14 deployed additional specific response mechanism different from FA, involving high induction of protease inhibitors, serine/threonine kinases, terpenoid, hormone signaling, and transport, which contributed to MA tolerance of LBD. Furthermore, inductions of pathogenesis-related proteins, LRR receptor-like kinases, mitogen-activated protein kinase, WRKY transcription factors, jasmonic acid, and phenolic compounds mediate E14 resistance against LBD. These proteins were confirmed at the transcription level by a quantitative polymerase chain reaction and at the translation level by western-blot. Conclusions We found several proteins that were differentially abundant among the cultivars, that includes common and cultivar specific proteins which highlighted similarities and significant differences between FA, MA, and E14 in terms of their defense response to PI. Here the specific accumulation of mitogen-activated protein kinase, Serine/threonine kinases, WRKY transcription played a positive role in E14 immunity against PI. The candidate proteins identified reported in this study will form the basis of future studies and may improve our understanding of the molecular mechanisms of late blight disease resistance in potato.

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There is currently no effective treatment for AD, which may be attributed in part to lack of a clear underlying mechanism. Studies within the last few decades provide growing evidence for a central role of amyloid β (Aβ) and tau, as well as glial contributions to various molecular and cellular pathways in AD pathogenesis. Herein, we review recent progress with respect to Aβ- and tau-associated mechanisms, and discuss glial dysfunction in AD with emphasis on neuronal and glial receptors that mediate Aβ-induced toxicity. We also discuss other critical factors that may affect AD pathogenesis, including genetics, aging, variables related to environment, lifestyle habits, and describe the potential role of apolipoprotein E (APOE), viral and bacterial infection, sleep, and microbiota. Although we have gained much towards understanding various aspects underlying this devastating neurodegenerative disorder, greater commitment towards research in molecular mechanism, diagnostics and treatment will be needed in future AD research.

The authors would like to correct an error in the original publication [...]

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.

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.

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.

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. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 45-year-old man with heart fatigue, shortness of breath, and frequent heart palpitations. Topics include clear breath sounds in both lungs, no dry and wet rales, normal heart, regular heart rhythm, no murmurs in each valve area, and mild edema of both lower extremities; and doubling decreased ventricular systolic function measurement values and pericardial effusion.

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]

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 Torini. In IKKϵ/TBK1 double-knock-out 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. [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 x-ray energies and transition rates associated with single and double electron radiative transitions from the double K hole state 2s2p to the 1s2s and 1s2 configurations of 11 selected He-like ions (10 ≤ Z ≤ 47) are calculated using the fully relativistic multi-configuration Dirac–Fock method (MCDF). An appropriate electron correlation model is constructed with the aid of the active space method, which allows the electron correlation effects to be studied efficiently. The contributions of the electron correlation and the Breit interaction to the transition properties are analyzed in detail. It is found that the two-electron one-photon (TEOP) transition is correlation sensitive. The Breit interaction and electron correlation both contribute significantly to the radiative transition properties of the double K hole state of the He-like ions. Good agreement between the present calculation and previous work is achieved. The calculated data will be helpful to future investigations on double K hole decay processes of He-like ions. [ABSTRACT FROM AUTHOR]

Electron-impact single ionization cross sections for Wq+ (q = 4–5) were calculated using the flexible atomic code (FAC) in the level-to-level distorted-wave method, considering the explicit branching ratio. The calculated cross sections are compared with the available theoretical and experiment results in detail. In the case of the contribution from the same channles as the available theoretical results, all of the calculated ionization cross sections agree with the experimental measured cross sections. But the present calculated results are larger than the experimental measurement when all channels contributions are included. Some important channels excitation autoionization (EA) contributions, such as the excitation to higher higher subshell from 4f and 5[s,p], were not included into the available theoretical calculation. In general, the distorted-wave (DW) results are overestimated. [ABSTRACT FROM AUTHOR]