Miracle-dz/UniFAR-FTUs huggingface dataset:
Behavioral features and disorganization of oscillatory activity in C57BL/6J mice after acute low dose MK-801 administration

Low dose acute administration of N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 is widely used to model cognition impairments associated with schizophrenia (CIAS) in rodents. However, due to no unified standards for animal strain, dose, route of drug delivery, and the duration of administration, how different doses of MK-801 influence behavior and fundamental frequency bands of the local field potential (LFP) in cortical and subcortical brain regions without consistent conclusions. The optimal dose of MK-801 as a valid cognition impairers to model CIAS in C57BL/6J mice remains unclear. The current study characterizes the behavior and neural oscillation alterations induced by different low doses of MK-801 in medial prefrontal cortex (mPFC) and hippocampus CA1 of C57BL/6J mice. The results reveal that mice treated with 0.1 and 0.3 mg/kg MK-801 demonstrate increased locomotion and diminished prepulse inhibition (PPI), while not when treated with 0.05 mg/kg MK-801. We also find that MK-801 dose as low as 0.05 mg/kg can significantly diminishes spontaneous alteration during the Y-maze test. Additionally, the oscillation power in delta, theta, alpha, gamma and HFO bands of the LFP in mPFC and CA1 was potentiated by different dose levels of MK-801 administration. The current findings revealed that the observed sensitivity against spontaneous alteration impairment and neural oscillation at 0.05 mg/kg MK-801 suggest that 0.05 mg/kg will produce changes in CIAS-relevant behavior without overt changes in locomotion and sensorimotor processing in C57BL/6J mice.
Cerebrospinal fluid micro-volume changes inside the spinal space affect intracranial pressure in different body positions of animals and phantom

Interpersonal differences can be observed in the human cerebrospinal fluid pressure (CSFP) in the cranium in an upright body position, varying from positive to subatmospheric values. So far, these changes have been explained by the Monroe–Kellie doctrine according to which CSFP should increase or decrease if a change in at least one of the three intracranial volumes (brain, blood, and CSF) occurs. According to our hypothesis, changes in intracranial CSFP can occur without a change in the volume of intracranial fluids. To test this hypothesis, we alternately added and removed 100 or 200 μl of fluid from the spinal CSF space of four anesthetized cats and from a phantom which, by its dimensions and biophysical characteristics, imitates the cat cerebrospinal system, subsequently comparing CSFP changes in the cranium and spinal space in both horizontal and vertical positions. The phantom was made from a rigid “cranial” part with unchangeable volume, while the “spinal” part was made of elastic material whose modulus of elasticity was in the same order of magnitude as those of spinal dura. When a fluid volume (CSF or artificial CSF) was removed from the spinal space, both lumbar and cranial CSFP pressures decreased by 2.0–2.5 cm H2O for every extracted 100 μL. On the other hand, adding fluid volume to spinal space causes an increase in both lumbar and cranial CSFP pressures of 2.6–3.0 cm H2O for every added 100 μL. Results observed in cats and phantoms did not differ significantly. The presented results on cats and a phantom suggest that changes in the spinal CSF volume significantly affect the intracranial CSFP, but regardless of whether we added or removed the CSF volume, the hydrostatic pressure difference between the measuring sites (lateral ventricle and lumbar subarachnoid space) was always constant. These results suggest that intracranial CSFP can be increased or decreased without significant changes in the volume of intracranial fluids and that intracranial CSFP changes in accordance with the law of fluid mechanics.
Elevation affects the ecological stoichiometry of Qinghai spruce in the Qilian Mountains of northwest China

Environmental heterogeneity in temperature, moisture, and soil fertility caused by elevation gradients can affect the trade-offs in the survival strategies of tree species. There is uncertainty about the allocation of resources to different tissues of trees in response to the elevation gradient with respect to carbon (C), nitrogen (N), and phosphorus (P). Here, the C, N, and P content of leaves, branches, trunks, and thick and fine roots of Picea crassifolia (Qinghai spruce) and their stoichiometric changes across three different elevations were investigated in the Qilian Mountains. We found that N:P of Qinghai spruce was <14 in all tissues at most elevations, indicating that Qinghai spruce was more susceptible to N limitation. Meanwhile, the N content and N:P of Qinghai spruce each were significantly negatively correlated with temperature (p < 0.05), and its P content was lower at high elevation. The contribution of soil–climate interactions on the elevation gradient to each tissue type was 34.02% (leaves), 16.84% (branches), 67.78% (trunks), 34.74% (thick roots), and 49.84% (fine roots), indicating that interacting climate and soil factors on the elevation gradient predominately drove the C, N, and P content and stoichiometry variation in each tissue type of Qinghai spruce trees. The results of this study clarify that the elevation gradient regulates the elemental content and resource allocation in Qinghai spruce, providing basic data and an important timely reference for future forest management in the regions where coniferous trees grows. These findings also help improve our understanding of elevational patterns of forest ecosystem stoichiometry in arid and semiarid regions.
Egg-inspired engineering in the design of thin-walled shelled vessels: a theoretical approach for shell strength

A novel subdiscipline of bionics is emerging in the form of ‘egg-inspired engineering’ through the use of egg-shaped ovoids as thin-walled tanks and building structures. Hügelschäffer’s and Narushin’s models of egg geometry are highly applicable within this proposed subdiscipline. Here we conducted a comparative analysis between the two models with respect to some of the most important egg parameters. These included contents volume, shell volume, and the location of the neutral axis along the shell thickness. As a first step, theoretical studies using the Narushin’s model were carried out due to the lack (or limited amount) of data on the geometric relationships of parameters and available calculation formulae. Considering experimental data accumulated in the engineering and construction industries, we postulate a hypothesis that there is a correlation between location of the neutral axis and the strength of the walls in the egg-shaped structure. We suggest that the use of Narushin’s model is preferable to Hügelschäffer’s model for designing thin-walled shelled vessels and egg-shaped building structures. This is due to its relative simplicity (because of the requirement for only two initial parameters in the basic equation), optimal geometry in terms of material costs per unit of internal capacity, and effective prerequisites for shell strength characteristics.
Safety of autologous freshly expanded mesenchymal stromal cells for the treatment of graft-versus-host disease

Despite the curative potential of hematopoietic cell transplantation (HCT) for hematologic malignancies, graft-versus-host disease (GVHD) remains a substantial cause of morbidity and mortality, particularly if treatment is refractory. Treatment with additional immunosuppression including steroids often leads to opportunistic infections and organ dysfunction. Novel therapies are greatly needed, specifically ones that lead to responses in treatment-refractory patients and are better tolerated. Mesenchymal stromal cells (MSCs) are non-hematopoietic tolerogenic cells present in normal bone marrow (BM), which can be expanded ex vivo to therapeutic doses. Their safety and efficacy have been assessed in inflammatory disorders including GVHD, but heterogeneity in clinical responses has led some to examine MSC manufacturing and administration procedures, which may impact in vivo efficacy. We hypothesized that autologous, early-passage, and culture-recovered (after freeze and thaw) MSCs would be safe and may have superior efficacy. In this phase I single-center trial, we assessed MSC safety and early efficacy of an escalating number of doses (2 × 106/kg doses; dose level 1, single dose; dose level 2, two weekly doses; dose level 3, four weekly doses) in patients aged ≥12 years with treatment-refractory acute or chronic GVHD. Eleven enrolled patients received some or all planned MSC infusions, with a median age at enrollment of 37 years. The most common primary HCT indication was leukemia, and the median time from HCT to first MSC infusion was 2.6 years. MSC infusion was well tolerated, with all severe adverse events expected and determined to be unlikely or definitely not related to the study. Thus, no dose-limiting toxicities occurred in the three dose levels. Three of four patients with acute GVHD (or overlap with acute features) had responses seen at any timepoint, ranging from partial to complete. In those with a chronic GVHD indication (n = 7), an overall response at 3 months was partial in five, stable in one, and progressive in one. No appreciable differences were seen between dose levels in peripheral blood lymphocyte subsets. In conclusion, autologous and culture-recovered MSCs were safe in the setting of refractory GVHD following HCT for hematologic malignancy, and clinical responses were most notable in patients with acute GVHD.
Contact varroacidal efficacy of lithium citrate and its influence on viral loads, immune parameters and oxidative stress of honey bees in a field experiment

With an almost global distribution, Varroa destuctor is the leading cause of weakening and loss of honey bee colonies. New substances are constantly being tested in order to find those that will exhibit high anti-Varroa efficacy at low doses/concentrations, without unwanted effects on bees. Lithium (Li) salts stood out as candidates based on previous research. The aims of this study were to evaluate Li citrate hydrate (Li-cit) for its contact efficacy against Varroa, but also the effect of Li-cit on honey bees by estimating loads of honey bee viruses, expression levels of immune-related genes and genes for antioxidative enzymes and oxidative stress parameters on two sampling occasions, before the treatment and after the treatment. Our experiment was performed on four groups, each consisting of seven colonies. Two groups were treated with the test compound, one receiving 5 mM and the other 10 mM of Li-cit; the third received oxalic acid treatment (OA group) and served as positive control, and the fourth was negative control (C group), treated with 50% w/v pure sucrose-water syrup. Single trickling treatment was applied in all groups. Both tested concentrations of Li-cit, 5 and 10 mM, expressed high varroacidal efficacy, 96.85% and 96.80%, respectively. Load of Chronic Bee Paralysis Virus significantly decreased (p < 0.01) after the treatment in group treated with 5 mM of Li-cit. In OA group, loads of Acute Bee Paralysis Virus and Deformed Wing Virus significantly (p < 0.05) increased, and in C group, loads of all viruses significantly (p < 0.01 or p < 0.001) increased. Transcript levels of genes for abaecin, apidaecin, defensin and vitellogenin were significantly higher (p < 0.05—p < 0.001), while all oxidative stress parameters were significantly lower (p < 0.05—p < 0.001) after the treatment in both groups treated with Li-cit. All presented results along with easy application indicate benefits of topical Li-cit treatment and complete the mosaic of evidence on the advantages of this salt in the control of Varroa.
Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection

Current coronavirus disease-19 (COVID-19) vaccines are administered by the intramuscular route, but this vaccine administration failed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection in the upper respiratory tract, mainly due to the absence of virus-specific mucosal immune responses. It is hypothesized that intranasal (IN) vaccination could induce both mucosal and systemic immune responses that blocked SARS-CoV-2 transmission and COVID-19 progression. Here, we evaluated in mice IN administration of three modified vaccinia virus Ankara (MVA)-based vaccine candidates expressing the SARS-CoV-2 spike (S) protein, either the full-length native S or a prefusion-stabilized [S(3P)] protein; SARS-CoV-2-specific immune responses and efficacy were determined after a single IN vaccine application. Results showed that in C57BL/6 mice, MVA-based vaccine candidates elicited S-specific IgG and IgA antibodies in serum and bronchoalveolar lavages, respectively, and neutralizing antibodies against parental and SARS-CoV-2 variants of concern (VoC), with MVA-S(3P) being the most immunogenic vaccine candidate. IN vaccine administration also induced polyfunctional S-specific Th1-skewed CD4+ and cytotoxic CD8+ T-cell immune responses locally (in lungs and bronchoalveolar lymph nodes) or systemically (in spleen). Remarkably, a single IN vaccine dose protected susceptible K18-hACE2 transgenic mice from morbidity and mortality caused by SARS-CoV-2 infection, with MVA-S(3P) being the most effective candidate. Infectious SARS-CoV-2 viruses were undetectable in lungs and nasal washes, correlating with high titers of S-specific IgGs and neutralizing antibodies against parental SARS-CoV-2 and several VoC. Moreover, low histopathological lung lesions and low levels of pro-inflammatory cytokines in lungs and nasal washes were detected in vaccinated animals. These results demonstrated that a single IN inoculation of our MVA-based vaccine candidates induced potent immune responses, either locally or systemically, and protected animal models from COVID-19. These results also identified an effective vaccine administration route to induce mucosal immunity that should prevent SARS-CoV-2 host-to-host transmission.
No association of GABRA1 rs2279020 and GABRA6 rs3219151 polymorphisms with risk of epilepsy and antiepileptic drug responsiveness in Asian and Arabic populations: Evidence from a meta-analysis with trial sequential analysis

The γ-aminobutyric acid type A receptors (GABAAR) have been reported to contribute to the pathogenesis of epilepsy and the recurrence of chronic seizures. Genetic polymorphisms in GABRA1 and GABRA6 may confer a high risk of epilepsy and multiple drug resistance, but with conflicting results. We aimed to assess the association of GABRA1 rs2279020 and GABRA6 rs3219151 with epilepsy risk using a meta-analysis. The databases of Pubmed, Ovid, Web of Science, and China National Knowledge Infrastructure were searched. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were computed to evaluate the association between the polymorphisms and epilepsy risk using a fixed- or random-effect model. Trial sequential analysis (TSA) was performed to assess the results of the meta-analysis. No significant association between the GABRA1 rs2279020 and GABRA6 rs3219151 and the risk of epilepsy was found in the Asian and Arabic populations. The negative results were also observed when comparing the GABRA1 rs2279020 and GABRA6 rs3219151 polymorphism to antiepileptic drug responsiveness. The trial sequential analysis confirmed the results of the meta-analysis. This meta-analysis suggests that GABRA1 rs2279020 and GABRA6 rs3219151 are not risk factors for the etiology of epilepsy and antiepileptic drug responsiveness in the Asian and Arabic populations.
Cuproptosis-related gene signature correlates with the tumor immune features and predicts the prognosis of early-stage lung adenocarcinoma patients

Background: Although a majority of early-stage lung adenocarcinoma (es-LUAD) patients have a favorable prognosis, there are still some cases with a risk of recurrence and metastasis. Cuproptosis is a new form of death that differs from other programmed cell death. However, no study has been reported for setting a prognostic model of es-LUAD using cuproptosis pattern-related genes. Methods: Using multiple R packages, the data from the GEO database was processed, and es-LUAD patients was classified into two patterns based on cuproptosis-related genes. Key differentially expressed genes (DEGs) in the two patterns were screened to construct a prognostic signature to assess differences in biological processes and immunotherapy responses in es-LUAD. Tumor microenvironment (TME) in es-LUAD was analyzed using algorithms such as TIMER and ssGSEA. Then, a more accurate nomogram was constructed by combining risk scores with clinical factors. Results: Functional enrichment analysis revealed that DEGs in two patterns were correlated with organelle fission, nuclear division, chromosome segregation, and cycle-related pathways. Univariate Cox regression and Lasso-Cox regression analyses identified six prognostic genes: ASPM, CCNB2, CDC45, CHEK1, NCAPG, and SPAG5. Based on the constructed model, we found that the high-risk group patients had higher expression of immune checkpoints (CTLA4, LAG3, PD-L1, TIGIT and TIM3), and a lower abundance of immune cells. Lastly, the nomogram was highly accurate in predicting the 1-, 3-, and 5-year survival status of patients with es-LUAD based on risk scores and clinical factors. Conclusion: The cuproptosis pattern-related signature can serve as a potential marker for clinical decision-making. It has huge potential in the future to guide the frequency of follow-up and adjuvant therapy for es-LUAD patients.
Comparative mitogenomic analyses provide evolutionary insights into the retrolateral tibial apophysis clade (Araneae: Entelegynae)

The retrolateral tibial apophysis (RTA) clade is the largest spider lineage within Araneae. To better understand the diversity and evolution, we newly determined mitogenomes of ten RTA species from six families and performed a comparative mitogenomics analysis by combining them with 40 sequenced RTA mitogenomes available on GenBank. The ten mitogenomes encoded 37 typical mitochondrial genes and included a large non-coding region (putative control region). Nucleotide composition and codon usage were well conserved within the RTA clade, whereas diversity in sequence length and structural features was observed in control region. A reversal of strand asymmetry in nucleotide composition, i.e., negative AT-skews and positive GC-skews, was observed in each RTA species, likely resulting from mitochondrial gene rearrangements. All protein-coding genes were evolving under purifying selection, except for atp8 whose Ka/Ks was larger than 1, possibly due to positive selection or selection relaxation. Both mutation pressure and natural selection might contribute to codon usage bias of 13 protein-coding genes in the RTA lineage. Phylogenetic analyses based on mitogenomic data recovered a family-level phylogeny within the RTA; {[(Oval calamistrum clade, Dionycha), Marronoid clade], Sparassidae}. This study characterized RTA mitogenomes and provided some new insights into the phylogeny and evolution of the RTA clade.
Are the concepts of emotion special? A comparison between basic-emotion, secondary-emotion, abstract, and concrete words

The study of emotional concepts stands at a very interesting intersection between the theoretical debate about the nature of emotions and the debate about the nature of processing concrete concepts and abstract concepts. On the one hand, it is debated whether it is possible to differentiate basic emotions from secondary emotions and, on the other hand, whether emotional concepts differ from abstract concepts. In this regard, the prototypical perceptual aspects are considered an important factor both for the differentiation between concrete and abstract concepts and for the differentiation between basic and secondary emotions (facial expressions). Thus, the objective has been to determine if (a) the presence or absence of a prototypical perceptual referent, and (b) the type of concept (referring to emotion and not referring to emotion), produce differences between concepts of basic emotions, secondary emotions and concepts not related to emotions, concrete and abstract, in the tasks of qualification of concreteness, imageability and availability of context and the task of the list of properties, that have been used in previous studies. A total of 86 university students from the suburbs of La Serena - Coquimbo (Chile), all native Spanish speakers, participated in the study. The results show that in the perception of concreteness and in the total of enumerated properties, emotional concepts presented similar results to abstract concepts not related to emotion and there was no difference between basic and secondary emotion concepts. In imageability and context availability, emotional concepts were perceived as different from and more concrete than abstract concepts. In addition, the cause-effect type attributes allowed to clearly differentiate emotional concepts from those not related to emotion and to differentiate between basic and secondary emotion concepts. These types of attributes appear almost exclusively in emotional concepts and are more frequent in basic emotions. These results are partially consistent with the predictions of Neurocultural and Conceptual Act theories about emotions.
Control of aging by the renin–angiotensin system: a review of C. elegans, Drosophila, and mammals

The free-living, non-parasitic nematode Caenorhabditis elegans is a premier model organism for the study of aging and longevity due to its short lifespan, powerful genetic tools, and conservation of fundamental mechanisms with mammals. Approximately 70 percent of human genes have homologs in C. elegans, including many that encode proteins in pathways that influence aging. Numerous genetic pathways have been identified in C. elegans that affect lifespan, including the dietary restriction pathway, the insulin/insulin-like growth factor (IGF) signaling pathway, and the disruption of components of the mitochondrial electron transport chain. C. elegans is also a powerful system for performing drug screens, and many lifespan-extending compounds have been reported; notably, several FDA-approved medications extend the lifespan in C. elegans, raising the possibility that they can also extend the lifespan in humans. The renin–angiotensin system (RAS) in mammals is an endocrine system that regulates blood pressure and a paracrine system that acts in a wide range of tissues to control physiological processes; it is a popular target for drugs that reduce blood pressure, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Emerging evidence indicates that this system influences aging. In C. elegans, decreasing the activity of the ACE homolog acn-1 or treatment with the ACE-inhibitor Captopril significantly extends the lifespan. In Drosophila, treatment with ACE inhibitors extends the lifespan. In rodents, manipulating the RAS with genetic or pharmacological interventions can extend the lifespan. In humans, polymorphisms in the ACE gene are associated with extreme longevity. These results suggest the RAS plays a conserved role in controlling longevity. Here, we review studies of the RAS and aging, emphasizing the potential of C. elegans as a model for understanding the mechanism of lifespan control.