Kidney transplantation recipients (KTRs) represent a vulnerable population for COVID-19 infection and severe disease. Nirmatrelvir-ritonavir has demonstrated efficacy in treating COVID-19 among KTRs, which interacts with tacrolimus leading to a precipitous increase in tacrolimus blood levels when co-administered, potentially resulting in toxicity. This study conducted a Real-world analysis of KTRs treated with nirmatrelvir-ritonavir for COVID-19 to investigate the relationship between tacrolimus levels and dosing during and within 10 days post-discontinuation of nirmatrelvir-ritonavir. In the experimental group, patients initiated tacrolimus at 20-25% of the baseline dose 48 hours after discontinuing nirmatrelvir-ritonavir, with daily increments of 20-25% until the baseline dose was restored. Patients who did not adhere to the experimental protocol were included in the control group. Findings indicated that withholding tacrolimus 12 hours prior to commencing nirmatrelvir-ritonavir maintained tacrolimus blood levels above 83% of the baseline throughout the nirmatrelvir-ritonavir treatment period. Compared to the control group, The experimental group achieved target trough concentrations of tacrolimus more rapidly and maintained a higher proportion within the therapeutic range ( p=0.029), and exhibited significantly lower rates of adverse events ( p<0.001). This investigation provides a safe and effective pharmacological strategy for KTRs infected with COVID-19, enabling the safe co-administration of nirmatrelvir-ritonavir and tacrolimus.

Terpenoids are the largest and diverse family of natural secondary metabolites that have attracted more attention from chemists and pharmacologists for their intriguing skeletons and broad biological activities, including anti-inflammatory, antitumoral, antimicrobial, and anti-viral effects. Based on the previous reviews, we did a comprehensive summary of recent advances of bioactive terpenoids, focusing on their intriguing structural features and promising biological activities, covering the literatures from 2020 to 2023. In this review, 543 terpenoids with remarkable chemical architectures and biological properties are classified as monoterpenoids (7), sesquiterpenoids (142), diterpenoids (129), sesterterpenoids (24), triterpenoids (52), meroterpenoids (167), and miscellaneous terpenoids (14), that were isolated from terrestrial and marine resources. This review would provide a reference for researchers to rapidly discover the interesting terpenoids for further study as promising drug leads

Abstract: Teachers’ policy satisfaction is essential to implement teacher education policy. However, research on how teachers’ policy satisfaction impacts teacher education policy implementation is limited. Thus, this study aims to investigate the factors that influence teachers’ policy satisfaction on teacher exchange rotation in China. A total of 14,859 (11,206 female, accounting for 75.42%) questionnaires were collected and analyzed. Principal–agent theory was the theoretical underpinning applied in this study. It was found that policy satisfaction is significantly positively affected by policy implementation, with an influence coefficient of 0.942, and policy implementation was significantly positively influenced by understanding policy publicity and policy effectiveness, with influence coefficients of 0.028 and 0.921, respectively. The scientific policy design and its highly related policy implementation are important to improving teachers’ satisfaction with the rotation exchange policy. The article concludes with a discussion.

Metastasis of Ewing Sarcoma to the Pancreas: An Exceedingly Rare Case report and Literature Review

We present a case of a 9-year-old child with a malignant epithelioid neoplasm located in the retroperitoneum that was found to have a fusion of the ESWR1/CREM genes, confirmed through anatomopathological examination, immunohistochemical, and molecular biology studies. While similar cases have been reported in the literature for adult patients, they are very rare in children and appear to represent a new type of tumor. Our case emphasizes the importance of the correlation between pathological anatomy and genetics.

Multiple primary malignancies (MPM )may arise in the same organ or differentsites of the body. Wepresent a challengingcase of non-small cell lung cancer (NSCLC) with metastatic subcutaneous nodule beneath the skin of the breast, coexisting with a second lesion in the breast tissue on the same side. The latter was confirmed later as a second primary invasive breast cancer. Generally, when a patient presents with a suspicious breast mass and a firm, possibly malignant subcutaneous nodule on the same breast, this situation guides the clinician to suspect breast cancer. However, in some atypical cases, metastasis might originate from another primary cancer site, such as the lung parenchyma. Here, we report this case to improve the management of similar cases and remind clinicians to always consider such rare possibilities.

Background: High expression levels of cluster of differentiation 47 (CD47) have been recognized as poor survival in several different cancers. Nevertheless, the significance of CD47 in patients with solid tumors remains controversial. Methods: This meta‑analysis was based on a search of PubMed, Embase and Web of Science databases to obtain 22 eligible published studies (totaling 4,204 patients) between January 2018 and January 2024. The combined hazard ratios (HRs) for overall survival (OS) were evaluated, and the HRs for relapse‑free survival (RFS), progression‑free survival (PFS), and disease‑free survival (DFS), as well as odds ratios for clinicopathological data, were also respectively combined. Results: The data obtained from these studies were extracted from these published studies and analyzed. This study suggested that CD47 overexpression was related to shorter OS times in human solid tumors, with a combined HR for OS (according to the univariate analysis) of HR=1.60 [95% confidence intervals (95% CI): 1.43‑1.79; P<0.00001], and a pooled HR for OS (according to the multivariate analysis) of HR=2.02 (95% CI: 1.43‑2.84; P<0.0001). The subgroup analysis revealed that CD47 overexpression was related with inferior OS rates according to country, cancer type, sample size, analysis type and the method via which the HR value was obtained (i.e., reported or extracted; P<0.05); in addition, a high expression level of CD47 was also a predictor of poor DFS, PFS and RFS rates (P<0.00001). Certain factors, such as lymph node metastasis, TNM staging, differentiation type, tumor recurrence and tobacco exposure, resulted in an upregulation of CD47 (P<0.05). Conclusion: CD47 overexpression was found to be significantly related with an advanced clinical stage, poor differentiation types and tobacco exposure, and may serve as a valuable biomarker for predicting worse prognosis in human solid tumors.

Pseudoaneurysm of the ascending aorta is rare but life-threatening. We report a case of a primary pseudoaneurysm originating from the ascending aorta that recurred six months after surgical treatment, and the patient eventually died of shock due to a rupture of the pseudoaneurysm. Furthermore, to the best of our knowledge this is the first reported case of Relapse of ascending aorta pseudoaneurysm to pulmonary arteriovenous fistula after first resection.In this article, we aim to provide detailed information on the different etiologies and presentations of pseudoaneurysms of the ascending aorta, highlighting the possibility and severity of pseudoaneurysms occurring in young patients.

Kawasaki disease (KD) is an acute systemic vasculitis that affects greater odds of coronary arteries. It is the primary cause of acquired heart disease in children in developed countries. We first describe a case of KD with septicemia caused by staphylococcus aureus in an adolescent patient who developed a severe complication, multiple giant coronary artery aneurysms with thrombosis. A combination of two-dimensional speckle tracking echocardiography (2D-STE) and exercise stress echocardiography(ESE) have potential benefits. In particular, we explore the possibility that regional longitudinal strain (LS) may predict inducible myocardial ischemia areas, and seem a promising tool of potential clinical value.

In bioinformatics, modeling the protein space to better predict function and structure has benefitted from Protein Language Models (PLMs). Their basis is the protein’s amino acid sequence and self-supervised learning. Ankh is a prime example of such a PLM. While there has been some recent work on integrating structure with a PLM to enhance predictive performance, to date there has been no work on integrating secondary structure rather than three-dimensional structure. Here we present TooT-PLM-P2S that begins with the Ankh model pre-trained on 45 million proteins using self-supervised learning. TooT-PLM-P2S builds upon the Ankh model by initially using its pre-trained encoder and decoder. It then undergoes an additional training phase with approximately 10,000 proteins and their corresponding secondary structures. This retraining process modifies the encoder and decoder, resulting in the creation of TooT-PLM-P2S. We then assess the impact of integrating secondary structure information into the Ankh model by comparing Ankh and TooT-PLM-P2S on eight downstream tasks including fluorescence and solubility prediction, sub-cellular localization, and membrane protein classification. For both Ankh and TooT-PLM-P2S the downstream tasks required task-specific training. Few of the results showed statistically significant differences. Ankh outperformed on three of the eight tasks, TooT-PLM-P2S did not outperform on any task for the primary metric. TooT-PLM-P2S did outperform for the precision metric for the task of discriminating membrane proteins from non-membrane proteins. This study requires future work with expanded datasets and refined integration methods.

The last few years have seen the rapid proliferation of machine learning- (ML) based binding protein design methods. Although these methods have shown large increases in experimental success rates compared to prior approaches, the majority of their predictions fail when experimentally tested. It is evident that computational methods still struggle to distinguish the features of real protein binding interfaces from false predictions. To identify features of interactions that should occur in protein binding interfaces, short molecular dynamics simulations of 20 antibody-protein complexes were conducted. Intermolecular salt bridges, hydrogen bonds, and hydrophobic interactions were evaluated for their persistences, energies, and stabilities during the simulations. It was determined that only hydrogen bonds where both residues are stabilized in the bound complex are expected to persist and contribute meaningfully to the binding between proteins. In contrast, stabilization was not a requirement for salt bridges and hydrophobic interactions to persist but interactions where both residues are stabilized in the bound complex persist significantly longer and have significantly stronger energies. Using a dataset of 220 real antibody- protein complexes and 8194 false complexes from docking, a random forest classifier was trained and tested using features of the expected persistent interactions and compared to one only using the complex-level features of interaction energy (IE), buried surface area (BSA), IE/BSA, and shape complementarity. Inclusion of the features of the expected persistent interactions reduced the false positive rate of the classifier by two to five fold across a range of true positive classification rates.

Background and Purpose Stress is a major risk factor for psychiatric disorders and significantly affects neuroplasticity in brain areas including the nucleus accumbens (NAc) and the insular cortex (IC). Here, we examined alterations in neuroplasticity within the aIC-NAc circuit following restraint stress in male and female rats, and determined the involvement of the endocannabinoid system in this response. Experimental Approach We subjected male and female rats to a 2h-period of acute restraint stress. Following this, we performed behavioral experiments, c-Fos immunohistochemistry and in vivo electrophysiological recordings of NAc neurons in response to aIC stimulation from anesthetized male and female rats immediately and 24h after stress exposure. Since the effect of stress was observed only in males, we evaluated the effects of blockade of cannabinoid CB1 receptors in male rats. Key Results We show that synaptic plasticity in the aIC-NAcC pathway differs between male and female rats. Under basal conditions, in males, long-term potentiation and long-term depression were equally induced, whereas in females, we found mostly a long-term potentiation. Moreover, stress affected synaptic plasticity in the aIC-NAcC only in males, inducing a loss of long-term-depression 24h after stress. Finally, blocking CB1 receptors in males restored long-term depression. Conclusion and Implications These results demonstrate that integration of aIC information to NAcC differs between males and females, that stress affects neuroplasticity only in males, an effect that depends on the endocannabinoid system. This study provides mechanistic support for differential reactivity to stress between males and females that may relate to stress-related psychiatric disorders.

Introduction

Lions and their prey are threatened across most of their range but especially in West and Central Africa. Prey availability influences carnivore densities, social structure, prey preference and home ranges, and changes in prey are important for carnivore management. Scarcity of large prey in many West and Central African ecosystems has been described as leading to a preference for hunting smaller prey in smaller groups. Here we investigated the changes in prey selection of lions in Zakouma National Park (Chad), a restored protected area in Central Africa, by collecting feeding data through opportunistic observations and GPS cluster points of lion collars. Compared to pre-restoration data, lions preferred larger prey and fed in larger groups. Our results show that diet shifts due to prey losses can be reversed with restoration of the ecosystem, and we speculate that this may be true across large carnivores and across regions.

Ball mills are commonly used in chemical and mineral processing industries for particle size reduction. In mineral processing, cylindrical drums with wear resistant materials are used various operation scales. Polygon shaped mills have found application by artisanal and small-scale miners (ASM) due technological and economic reasons. Evaluating this kind of mills is key in improving or replacing them based on technological data. A modest improvement in grinding efficiency and mill durability can lead to significant economic and environmental benefits. In this study, the performance of polygonal shaped mills was evaluated and compared with cylindrical profiles considering power draw, collision energy dissipation, relative wear and operational stability. Discrete element method (DEM) was used to carry out simulations to describe mechanical behavior of grinding media and the interaction with the mill walls. Polygonal shaped mills without lifters promoted more interparticle interaction with limited centrifuging of particle even at higher speeds compared to cylindrical mills without lifters. Installation of lifters in polygon increased inter-particle collisions and reduce power draw and relative wear. Cylindrical mill with lifters had high interparticle collisions similar to polygonal profile with much lower cumulative relative wear and high operational stability.

Monitoring cell culture is crucial for gaining a deeper understanding of processes and ensuring the production of safe and high-quality products. The capability to measure in real-time several parameters of interest can be achieved with Raman spectroscopy. However, before using Raman spectroscopy to monitor a specific process, a calibration phase is required to develop chemometric models that correlate Raman spectra with the target parameters. It is mandatory to conduct this phase with multiple batches to build robust models that account for biological variability. This model building phase can be time-consuming and require a lot of resources. The industry is actively seeking solutions to simplify and expedite this step without compromising accuracy. Moreover, the current approach has limitations regarding changing cell culture media, cell-line, or process scale. The novel synthetic model approach provides a significant gain of time and resources for the calibration phase which is reduced to just a few days. The methodology involves using cell-free samples of cell culture media that are spiked with various concentrations of target compounds. The results indicate that the innovative approach enables accurate measurement for glucose and lactate parameters in real process conditions comparable to a standard modeling methodology.

Adaptive radiations are rich laboratories for exploring, testing, and understanding key theories in evolution and ecology because they offer spectacular displays of speciation and ecological adaptation. Particular challenges to the study of adaptive radiation include high levels of species richness, rapid speciation, and gene flow between species. Over the last decade, high-throughput sequencing technologies and access to population genomic data have lessened these challenges by enabling the analysis of samples from many individual organisms at whole-genome scales. Here we review how population genomic data have facilitated our knowledge of adaptive radiation in five key areas: 1) phylogenetics, 2) hybridization, 3) timing and rates of diversification, 4) genomic basis of trait evolution, and 5) the role of genome structure in divergence. We review current knowledge in each area, highlight outstanding questions, and focus on methods that facilitate detection of complex patterns in population evolutionary demography. Among patterns that emerge, we particularly note that hybridization—and the hypothesized processes by which it shapes diversification—and questions seeking to bridge the divide between microevolutionary and macroevolutionary processes as rich areas for future study. Overall, access to population genomic data have facilitated an exciting era in adaptive radiation research, with implications for deeper understanding of fundamental evolutionary processes across the tree of life.

The CRISPR-Cas9 system is extremely useful for genome editing in many species, including the model yeast Saccharomyces cerevisiae, and other yeast species. We have previously reported the use of an inducible CRISPR-Cas9 system in Candida glabrata, which allows genome editing but also the study of Double Strand Break (DSB) repair. We report, in this study, a comparable system for C. glabrata, relying on a new plasmid, which is more stable than the previous one. We also report the use of this plasmid to induce DSBs in two additional human pathogens, Candida bracarensis and Candida nivariensis. We examine lethality induced by an in vivo DSB in the three species and describe the different types of Non-Homologous End-Joining (NHEJ) events detected in these three pathogens.

Note: Graphene has certain electrical properties that make it a promising candidate for future nanoelectronics. While graphene, a single-dimensional carbon layer, is a conductive material, it can be converted into a semiconductor as a nanowire. This means that it has enough energy or a band gap in which there is no electron mode - it can be turned on and off, and therefore may become a major component of nanotransistors.The role of graphene nano-plates (GA) in the construction of Nano Transistors as  an electric field generated by the gate electrode controls the current generated by the two electrodes source and drain. The drain current is modulated by changing the density of the charge carriers in the two-dimensional transmission channel. In the nanotransistor, the effect of a multi-layer Si graphene field is modulated by a three-dimensional transmission channel with a three-dimensional transmission channel thicknessn the circuit diagram of a multilayer GA graphene field effect nanotransistor, the two source and drain electrodes are connected directly to the semiconductor, while the gate electrode is capacitively connected to the semiconductor using a dielectric gate.

Note: In the structure ( nanotransistors) of Nano transistors, the electronic quantity that is more easily availableis the ionization potential, and in the ionization potential in the size  of small nanostructures (smaller particles) is more, ie with increasing particle size, their ionization potential decreases. Finds.Increasing the surface-to- volume ratio and  changes in electronic geometry and structure have a strong effect on the chemical interactions of matter, and for example the activity of small particles  changes with the number of atoms (and therefore the particle size). Unlike today's nanotransistors, which behave based on the mass motion of electrons in matter, new devices follow the phenomena of nanoscale quantum mechanics in which the discrete nature of the electron can no longer be ignored. By shrinking all the horizontal and vertical dimensions of the transistor, the electric charge density in the various regions of the nanotransistor  increases, or in other words, the number of electrical charges per unit area of the nanotransistor increases.

Based on partial Fourier series analysis, we adapt on a model case a new approach to classical results obtained in the literature describing the singularities of a family a solutions of a second order elliptic problems on open non-convex planar sectors. The method allows the exhibition of singular and regular frequencies, explicit decomposition and description of coefficients of singularities of the solution. As a main result, explicit and sharp estimates with respect to the opening angle parameter are obtained via this method. They are not uniform near π where corners have opening angle generating a jump of singularity in Sobolev exponent, contrarily to the results obtained in A. Tami (2016),(2019),(2021) for harmonic and/or biharmonic problems on a family of convex planar sectors.

A major challenge in ecology is to understand how different species interact to determine ecosystem function, particularly in communities with large numbers of co-occurring species. We use a trait-based model of microbial litter decomposition to quantify how different taxa impact ecosystem function. Further, we build a novel framework that highlights the interplay between taxon traits and environmental conditions, focusing on their combined influence on community interactions and ecosystem function. Our results suggest that the impact of a taxon is driven by its resource acquisition traits and the community functional capacity, but that physiological stress amplifies the impact of both positive and negative interactions. Further, net positive impacts on ecosystem function can arise even as microbes have negative pairwise interactions with other taxa. As communities shift in response to global climate change, our findings reveal the potential to predict the biogeochemical functioning of communities from taxon traits and interactions.

Objectives: The prodromal phase of a psychotic disorder is a period of altered functioning before the onset of the acute state; several interviews have been developed to determine whether individuals present with prodromal symptoms. The 16-item Prodromal Questionnaire (PQ-16) is a screening tool for evaluating those at risk of developing a psychotic disorder. The study aimed to evaluate the psychometric properties of the Latvian version of the PQ-16 in a sample of help-seeking adolescents referred for diagnostic assessment and look for possible associated socio-demographic and health-related factors. Methods: A cross-sectional study included patients admitted for evaluation between November 2022 and February 2023 in Riga’s Children’s Clinical University Hospital Child Psychiatry clinic. The data were collected during outpatient consultations by mental health professionals. We used the Latvian translation of PQ-16 and the socio-demographic and health-related factors questionnaire. Data were analyzed with IBM SPSS 28; the scale’s diagnostic accuracy and internal validity were examined. Results: The study involved 107 adolescents aged 12 to 17, 80.5% female, with a mean age of 14.98 (CI 14.70-15.26). Socio-demographic data and health-related variables did not significantly differ between the sexes (p>.05). The Latvian PQ-16 demonstrated excellent internal reliability with a Cronbach’s Alpha of 0.890. All 16 items were found to be valid with p<.001. A significant number of participants (73.8%) scored above the current cut-off of ≥6 with a mean of 9.17 (95% CI 8.41-9.93). Certain socio-demographic factors, such as female gender (p<.001), fair school performance (p=.048), and recent changes in school performance (p<.001), demonstrated a significant association with higher scores. Additionally, there were found significant associations between positive screening and health-related factors such as obstetric complications (p=.044), smoking (p=.002), alcohol consumption (p=.021), history of bullying in school (p<.001), and emotional abuse at home (p=.011). Conclusions: Latvian translation of PQ-16 showed high internal reliability and validity levels. Positive PQ-16 screening was associated with female gender, worsened school performance, obstetric complications, substance abuse, and experienced emotional violence. The average score of 9.17 positive answers and 73.8% of participants screening positive for attenuated psychotic symptoms is significantly higher than in recent studies under similar conditions.

Cerebral ischemic disease is the most common cerebrovascular disease, especially ischemic stroke. Exercise has a protective function on brain tissues following cerebral ischemia-reperfusion injury (CIRI), but its preventive effect and mechanism in CIRI remain unclear. This research aimed to investigate the effect and mechanism of exercise preconditioning on CIRI. The middle cerebral artery occlusion (MCAO) operation was prepared to set up CIRI rats. All rats were randomized into the MCAO, exercise (exercise preconditioning plus MCAO operation), vector (exercise preconditioning, MCAO operation plus intraventricular injection of empty vector), and tissue inhibitor of metalloprotease 1 overexpression (OE-TIMP1) groups (exercise preconditioning, MCAO operation plus intraventricular injection of OE-TIMP1). The results indicated that exercise preconditioning effectively suppressed the brain dysfunction and TIMP1 mRNA level in MCAO rats, which was partially offset by OE-TIMP1. Also, the attenuation of exercise on the neuron death status and the infarction size in MCAO rats was counteracted by OE-TIMP1. This study also confirmed that exercise weakened apoptosis and oxidative stress damage, with a notable increase of Bcl-2, superoxide dismutase, and glutathione peroxidase production, and an evident decrease of Bax, caspase 3, and malondialdehyde in MCAO rats, while the effect was partially reversed after overexpressing TIMP1. Additionally, the down-regulation of exercise on the protein levels of TIMP1, hypoxia-inducible factor-alpha, vascular endothelial growth factor receptor-2, VEGF, and Notch 1 in MCAO rats was partially reversed by OE-TIMP1. Altogether, exercise preconditioning had protective effects on CIRI by restraining TIMP1. This study provides new targets and therapeutic strategies for the prevention of CIRI.