Fuel source shift or cost reduction: Context-dependent adaptation strategies in closely related Neodon fuscus and Lasiopodomys brandtii against hypoxia.

Oxygen is essential for most life forms. Insufficient oxygen supply can disrupt homeostasis and compromise survival, and hypoxia-induced cardiovascular failure is fatal in many animals, including humans. However, certain species have adapted and evolved to cope with hypoxic environments and are therefore good models for studying the regulatory mechanisms underlying responses to hypoxia. Here, we explored the physiological and molecular responses of the cardiovascular system in two closely related hypoxia-adapted species with different life histories, namely, Qinghai voles ( Neodon fuscus) and Brandt's voles ( Lasiopodomys brandtii), under hypoxic (10% O 2 for 48 h) and normoxic (20.9% O 2 for 48 h) exposure. Kunming mice ( Mus musculus) were used for comparison. Qinghai voles live in plateau areas under hypoxic conditions, whereas Brandt's voles only experience periodic hypoxia. Histological and hematological analyses indicated a strong tolerance to hypoxia in both species, but significant cardiac tissue damage and increased blood circulation resistance in mice exposed to hypoxia. Comparative transcriptome analysis revealed enhanced oxygen transport efficiency as a coping mechanism against hypoxia in both N. fuscus and L. brandtii, but with some differences. Specifically, N. fuscus showed up-regulated expression of genes related to accelerated cardiac contraction and angiogenesis, whereas L. brandtii showed significant up-regulation of erythropoiesis-related genes. Synchronized up-regulation of hemoglobin synthesis-related genes was observed in both species. In addition, differences in cardiometabolic strategies against hypoxia were observed in the rodents. Notably, M. musculus relied on adenosine triphosphate (ATP) generation via fatty acid oxidation, whereas N. fuscus shifted energy production to glucose oxidation under hypoxic conditions and L. brandtii employed a conservative strategy involving down-regulation of fatty acid and glucose oxidation and a bradycardia phenotype. In conclusion, the cardiovascular systems of N. fuscus and L. brandtii have evolved different adaptation strategies to enhance oxygen transport capacity and conserve energy under hypoxia. Our findings suggest that the coping mechanisms underlying hypoxia tolerance in these closely related species are context dependent.

Recent advances in the discovery and development of glyoxalase I inhibitors.

Glyoxalase I (GLO1) is a homodimeric Zn2+-metalloenzyme that catalyses the transformation of methylglyoxal (MG) to d-lacate through the intermediate S-d-lactoylglutathione. Growing evidence indicates that GLO1 has been identified as a potential target for the treatment cancer and other diseases. Various inhibitors of GLO1 have been discovered or developed over the past several decades including natural or natural product-based inhibitors, GSH-based inhibitors, non-GSH-based inhibitors, etc. The aim of this review is to summarize recent achievements of concerning discovery, design strategies, as well as pharmacological aspects of GLO1 inhibitors with the target of promoting their development toward clinical application.

Preexisting chronic conditions for fatal outcome among SFTS patients: An observational Cohort Study.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus SFTSV. Currently our knowledge of the host-related factors that influence the pathogenesis of disease is inadequate to allow prediction of fatal outcome. Here we conducted a prospective study of the largest database on the SFTS patients, to identify the presence of comorbidities in SFTS, and estimate their effect on the fatal outcome. Among 2096 patients eligible for inclusion, we identified nine kinds of comorbidities, from which hyperlipidemia (12.2%; 95% CI: 10.8%-13.6%), hypertension (11.0%; 95% CI: 9.6%-12.3%), chronic viral hepatitis (CVH) (9.3%; 95% CI: 8.1%-10.5%), and diabetes mellitus (DM) (6.8%; 95% CI: 5.7%-7.9%) were prevalent. Higher risk of death was found in patients with DM (adjusted OR = 2.304; 95% CI: 1.520-3.492; P<0.001), CVH (adjusted OR = 1.551; 95% CI: 1.053-2.285; P = 0.026) and chronic obstructive pulmonary diseases (COPD) (adjusted OR = 2.170; 95% CI: 1.215-3.872; P = 0.009) after adjusting for age, sex, delay from disease onset to admission and treatment regimens. When analyzing the comorbidities separately, we found that the high serum glucose could augment diseases severity. Compared to the group with max glucose < 7.0 mmol/L, patients with glucose between 7.0-11.1 mmol/L and glucose ≥11.1 mmol/L conferred higher death risk, with the adjusted OR to be 1.467 (95% CI: 1.081-1.989; P = 0.014) and 3.443 (95% CI: 2.427-4.884; P<0.001). Insulin therapy could effectively reduce the risk of severe outcome in DM patients with the adjusted OR 0.146 (95% CI: 0.058-0.365; P<0.001). For CVH patients, severe damage of liver and prolongation of blood coagulation time, as well as high prevalence of bleeding phenotype were observed. These data supported the provocative hypothesis that treating SFTS related complications can attain potentially beneficial effects on SFTS.

[Preparation optimization of extract of Moringa oleifera leaves and its immune regulation effect on immunosuppressed mice].

With total flavonoid content and dry extract yield as the observation indexes, the optimal extraction conditions of Moringa oleifera leaves were determined by using single factor test and orthogonal test, and cyclophosphamide modeling method was used to establish immunosuppressed mice models, so as to investigate the effects of M. oleifera leaves extract on immune regulation in mice. The results showed that the optimal preparation conditions were as follows: extraction with 70% ethanol, material-liquid ratio 1:15, extraction temperature 80 °C, three times, 1.5 hours for each time. Under these conditions, the content of total flavonoids from M. oleifera leaves was 15.64 mg·g⁻¹, which can significantly enhance macrophage phagocytosis and immune organ index, promote the synthesis of serum immunoglobulin IgG and hemolysin, and decrease AST activity, with regulation effect on immune dysfunction.

Interactive Visualization for Patient-to-Patient Comparison.

A visual analysis approach and the developed supporting technology provide a comprehensive solution for analyzing large and complex integrated genomic and biomedical data. This paper presents a methodology that is implemented as an interactive visual analysis technology for extracting knowledge from complex genetic and clinical data and then visualizing it in a meaningful and interpretable way. By synergizing the domain knowledge into development and analysis processes, we have developed a comprehensive tool that supports a seamless patient-to-patient analysis, from an overview of the patient population in the similarity space to the detailed views of genes. The system consists of multiple components enabling the complete analysis process, including data mining, interactive visualization, analytical views, and gene comparison. We demonstrate our approach with medical scientists on a case study of childhood cancer patients on how they use the tool to confirm existing hypotheses and to discover new scientific insights.

[Effects of different water and fertilizer supply on cucumber soil nutrient content, enzyme activity, and microbial diversity].

With cucumber (Cucumis sativus L.) variety Jinyou 1 as test material, a greenhouse experiment was conducted to study the effects of different water and fertilizer supply on the cucumber soil nutrient content, enzyme activity, and microbial diversity. Three water regimes (50%-60%, 70%-80%, and 90%-100% soil relative moisture content) and two fertilization practices (600 kg N x hm(-2) + 420 kg P2O5 x hm(-2) and 420 kg N x hm(-2) + 294 kg P2O5 x hm(-2)) were designed. The increase of water and fertilizer supply benefited the increase of soil available P content and sucrase activity. Increasing fertilization rate increased soil NH(4+)-N content but decreased soil protease activity, and increasing soil relative moisture content decreased the soil NH(4+)-N content and urease activity. Soil microbial diversity had no significant correlations with soil nutrient contents, but significantly positively correlated with soil urease activity and negatively correlated with soil sucrase activity. Among the treatments, the treatment 70%-80% soil relative moisture content + 600 kg N x hm(-2) and 420 kg P2O5 x hm(-2) had the highest soil nutrient contents, soil urease, sucrase, and phosphatase activities, and soil microbial diversity and evenness, being the best in soil potential productivity.

Nanometer-Thick Single-Crystal Hexagonal Gd2 O3 on GaN for Advanced Complementary Metal-Oxide-Semiconductor Technology.

Hexagonal-phase single-crystal Gd2 O3 is deposited on GaN in a molecular beam epitaxy system. The dielectric constant is about twice that of its cubic counterpart when deposited on InGaAs or Si. The capacitive effective thickness of 0.5 nm in hexagonal Gd2 O3 is perhaps the lowest on GaN-metal-oxide-semiconductor devices. The heterostructure is thermo dynamically stable at high temperatures and exhibits low interfacial densities of states after high-temperature annealing.