Spatial and single-nucleus transcriptomics decoding the molecular landscape and cellular organization of avian optic tectum.

The avian optic tectum (OT) has been studied for its diverse functions, yet a comprehensive molecular landscape at the cellular level has been lacking. In this study, we applied spatial transcriptome sequencing and single-nucleus RNA sequencing (snRNA-seq) to explore the cellular organization and molecular characteristics of the avian OT from two species: Columba livia and Taeniopygia guttata. We identified precise layer structures and provided comprehensive layer-specific signatures of avian OT. Furthermore, we elucidated diverse functions in different layers, with the stratum griseum periventriculare (SGP) potentially playing a key role in advanced functions of OT, like fear response and associative learning. We characterized detailed neuronal subtypes and identified a population of FOXG1+ excitatory neurons, resembling those found in the mouse neocortex, potentially involved in neocortex-related functions and expansion of avian OT. These findings could contribute to our understanding of the architecture of OT, shedding light on visual perception and multifunctional association.

Physiological indices and liver gene expression related to glucose supply in Brandt's vole (Lasiopodomys brandtii) exhibit species- and oxygen concentration-specific responses to hypoxia.

Brandt's vole (Lasiopodomys brandtii) is a species with hypoxia tolerance, and glucose serves as the primary energy substrate under hypoxia. However, the glucose supply in Brandt's voles under hypoxia has not been studied. This study aimed to investigate characteristics in physiological indices and liver gene expression associated with glucose supply in Brandt's voles under hypoxia. Serum glucose of Brandt's voles remained stable under 10% O2, increased under 7.5% O2, and decreased under 5% O2. Serum lactate increased under 10% O2, decreased under 7.5% O2, increased at 6 h and decreased at 12 h under 5% O2. Liver glycogen increased under 10% O2, remained constant under 7.5% O2, and reduced under 5% O2. Pepck and G6pase expression associated with gluconeogenesis decreased under 10% O2, while Pepck expression decreased and G6pase expression increased under 7.5% and 5% O2. Regarding genes related to glycogen metabolism, Gys expression decreased at all oxygen concentrations, Phk expression increased under 5% O2, and Gp expression increased under 7.5% and 5% O2. The alterations in glucose, lactate, liver glycogen, and gene expression related to glycogenolysis in Kunming mice (Mus musculus, control species) are similar to discovery of Brandt's voles under 7.5% O2, but gene expression involved in gluconeogenesis and glycogen synthesis increased. The findings suggest that Brandt's voles are more tolerant to hypoxia than Kunming mice, and their physiological indices and liver gene expression related to glucose supply exhibit species- and oxygen concentration-specific responses to hypoxia. This research offers novel insights for studying hypoxia tolerance of Brandt's voles.

Hypoxic response patterns in lung tissue: An integrated analysis of comparative physiological and transcriptomic studies from Neodon fuscus and Lasiopodomys brandtii.

Oxygen (O2) is essential for the survival and reproduction of most species. However, in recent years, with global climate change and the increasing impact of human activities on the ecosystem, the frequency of extreme environmental events, such as heat waves, cold waves, droughts, and floods, has increased, resulting in dramatic changes in environmental oxygen concentration (hypoxic environment, etc.), threatening the survival of animals and pushing them toward extreme adaptation. In this context, how organisms, especially those with differences in original habitats, adapt to low oxygen environment is particularly important. In this study, we systematically analyzed hypoxic response patterns in lung tissues of small rodents Neodon fuscus, Lasiopodomys brandtii, and Mus musculus with different experiences of natural hypoxia tolerance through laboratory simulation of hypoxia environment, combined with hematological, histological, and transcriptomic analysis. Our results show that all three species exhibit increased antioxidant defense and damage repair ability to a certain extent under hypoxia, although the specific molecular mechanisms are not the same. L. brandtii showed better damage repair ability than the others, which is likely to be closely related to the intermittent hypoxia environment experienced in the natural environment, and genes such as Glrx5, Prdx2, Col1a1, Lama1, and Eln may play a crucial role in this process. In addition, we found that both N. fuscus and L. brandtii appropriately enhanced oxygen transport in tissues under hypoxic conditions, with a series of functional genes related to hemoglobin synthesis and vascular smooth muscle contraction were significantly up-regulated in both species of voles, such as Actg2, Ptgir, Alas2, Hba, Hbb and Bpgm. Our results, to a certain extent, reveal the differences and similarities of hypoxic response patterns in lung tissues of small rodents with different hypoxic life histories and provide a relatively perfect analytical paradigm for related studies.

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.

Antioxidant response to severe hypoxia in Brandt's vole Lasiopodomys brandtii.

The antioxidant defense system is essential for animals to cope with homeostasis disruption and overcome oxidative stress caused by adverse environmental conditions such as hypoxia. However, our understanding of how this system works in subterranean rodents remains limited. In this study, Brandt's vole Lasiopodomys brandtii was exposed to normoxia (21% O2 ) or hypoxia (mild or severe hypoxia: 10% or 5% O2 ) for 6 h. Changes in key enzymes of the classic enzymatic antioxidant system at both mRNA and enzyme activity levels, and tissue antioxidant levels of the low-molecular-weight antioxidant system were determined in brain, liver, and kidney. Transcript levels of the upstream regulator NF-E2-related factor 2 (Nrf2) were also measured. We found that the mRNA expression of Nrf2 and its downstream antioxidant enzyme genes in L. brandtii were relatively conserved in response to hypoxia in most tissues and genes tested, except in the liver. Hepatic Nrf2, Cu/Zn SOD, GPx1, and GPx3 levels were significantly upregulated in response to mild hypoxia, whereas Mn SOD level decreased significantly in severe hypoxia. Unmatched with changes at the RNA level, constitutively high and relatively stable antioxidant enzyme activities were maintained throughout. For the low-molecular-weight antioxidant system, an abrupt increase of cerebral ascorbic acid (AA) levels in hypoxia indicated a tissue-specific antioxidant response. Although hypoxia did not cause significant oxidative damage in most tissues tested, the significant decrease in antioxidant enzyme activities (GPX and GR) and increase in lipid peroxidation in the kidney suggest that prolonged hypoxia may pose a critical threat to this species.

High energy switchable pulsed High-order Mode beams in a mode-locking Raman all-fiber laser with high efficiency.

High energy pulsed High-order Mode (HOM) beams has great potential in materials processing and particle acceleration. We experimentally demonstrate a high energy mode-locking Raman all-fiber laser with switchable HOM state. A home-made fiber mode-selective coupler (MSC) is used as the mode converter with a wide bandwidth of 60 nm. By combining advantages of MSC and stimulated Raman scattering, 1.1 µJ pulsed HOM beams directly emitting from the all-fiber cavity can be achieved. After controlling the category and phase delay of vector modal superposition, different pulsed HOM beams including cylindrical vector beams (CVBs) (radial and angular) and optical vortex beams (OVBs) are reasonably obtained with high purity (all over 95%), as well as arbitrary switching. Furtherly, the slope efficiency of HOM beams in the mode-locking and continuous wave operations are as much as 20.3% and 31.8%, respectively. It may provide an effective way to achieve high energy pulsed HOM beams.

Oleanolic acid inhibits the migration and invasion of hepatocellular carcinoma cells by promoting microRNA-122 expression.

MicroRNAs are emerging as important endogenous regulators of gene function and they are playing an important role in the occurrence and development of cancer. They are also regarded as robust biomarkers of cancer diagnosis and prognosis. Hepatocellular carcinoma (HCC) is a common and complex human malignancy with high mortality and morbidity in the world. MicroRNA-122 (miR-122) is a liver-specific microRNA and is closely associated with HCC metastasis, which makes miR-122 a promising target for drug design and development. In this study, we performed a cell-based screening method for discovering miR-122 activators and found that oleanolic acid (OA), a natural pentacyclic triterpene, specifically increased miR-122 expression in a concentration-dependent manner. Two HCC cell lines (HepG2 and Sk-hep-1 cells) were used to evaluate the effect of OA on cell migration and invasion abilities. The results indicated that OA attenuated the migration and invasion abilities of HCC cells by upregulating miR-122 expression. In addition, OA increased the expression of E-cadherin and decreased the expression of ß-catenin, N-cadherin and vimentin. After knocking down miR-122 with miR-122 inhibitor, we found that the effect of OA on these epithelial-to-mesenchymal transition (EMT) related molecules was significantly weakened, indicating OA exhibited anti-EMT effect by increasing the expression of miR-122. These finding may help to better understand the molecular mechanism of OA's anti-metastasis activity.

Diverse energy metabolism patterns in females in Neodon fuscus, Lasiopodomys brandtii, and Mus musculus revealed by comparative transcriptomics under hypoxic conditions.

The effects of global warming and anthropogenic disturbance force animals to migrate from lower to higher elevations to find suitable new habitats. As such migrations increase hypoxic stress on the animals, it is important to understand how plateau- and plain-dwelling animals respond to low-oxygen environments. We used comparative transcriptomics to explore the response of Neodon fuscus, Lasiopodomys brandtii, and Mus musculus skeletal muscle tissues to hypoxic conditions. Results indicate that these species have adopted different oxygen transport and energy metabolism strategies for dealing with a hypoxic environment. N. fuscus promotes oxygen transport by increasing hemoglobin synthesis and reduces the risk of thrombosis through cooperative regulation of genes, including Fga, Fgb, Alb, and Ttr; genes such as Acs16, Gpat4, and Ndufb7 are involved in regulating lipid synthesis, fatty acid ß-oxidation, hemoglobin synthesis, and electron-linked transmission, thereby maintaining a normal energy supply in hypoxic conditions. In contrast, the oxygen-carrying capacity and angiogenesis of red blood cells in L. brandtii are promoted by genes in the CYP and COL families; this species maintains its bodily energy supply by enhancing the pentose phosphate pathway and mitochondrial fatty acid synthesis pathway. However, under hypoxia, M. musculus cannot effectively transport additional oxygen; thus, its cell cycle, proliferation, and migration are somewhat affected. Given its lack of hypoxic tolerance experience, M. musculus also shows significantly reduced oxidative phosphorylation levels under hypoxic conditions. Our results suggest that the glucose capacity of M. musculus skeletal muscle does not provide sufficient energy during hypoxia; thus, we hypothesize that it supplements its bodily energy by synthesizing ketone bodies. For the first time, we describe the energy metabolism pathways of N. fuscus and L. brandtii skeletal muscle tissues under hypoxic conditions. Our findings, therefore, improve our understanding of how vertebrates thrive in high altitude and plain habitats when faced with hypoxic conditions.

Dietary daidzein inhibits hepatitis C virus replication by decreasing microRNA-122 levels.

MicroRNAs are emerging as critical endogenous regulators of gene function. Aberrant regulation of microRNAs is associated with various human diseases, most importantly cancer. MicroRNA-122 (miR-122), a liver-specific microRNA, has been implicated in the control of hepatitis C virus (HCV) RNA replication and its response to interferon (IFN) in human hepatoma cells. Here, we report that daidzein, a naturally occurring plant isoflavone, inhibits HCV replication and enhances the antiviral effect of IFN-α on HCV therapy by decreasing microRNA-122 levels in vitro without significantly affecting cell growth. Moreover, daidzein was found to inhibit the expression of miR-122 and miR-21 by down-regulating the expression of TRBP, indicating that daidzein is possibly a general inhibitor of the miRNA pathway. Thus, daidzein provides new insights for drug discovery and HCV prevention.

Influence of Optimization Design Based on Artificial Intelligence and Internet of Things on the Electrocardiogram Monitoring System.

With the increasing emphasis on remote electrocardiogram (ECG) monitoring, a variety of wearable remote ECG monitoring systems have been developed. However, most of these systems need improvement in terms of efficiency, stability, and accuracy. In this study, the performance of an ECG monitoring system is optimized by improving various aspects of the system. These aspects include the following: the judgment, marking, and annotation of ECG reports using artificial intelligence (AI) technology; the use of Internet of Things (IoT) to connect all the devices of the system and transmit data and information; and the use of a cloud platform for the uploading, storage, calculation, and analysis of patient data. The use of AI improves the accuracy and efficiency of ECG reports and solves the problem of the shortage and uneven distribution of high-quality medical resources. IoT technology ensures the good performance of remote ECG monitoring systems in terms of instantaneity and rapidity and, thus, guarantees the maximum utilization efficiency of high-quality medical resources. Through the optimization of remote ECG monitoring systems with AI and IoT technology, the operating efficiency, accuracy of signal detection, and system stability have been greatly improved, thereby establishing an excellent health monitoring and auxiliary diagnostic platform for medical workers and patients.

Glyoxalase system: A systematic review of its biological activity, related-diseases, screening methods and small molecule regulators.

The glyoxalase system is a ubiquitous enzymatic network which plays important roles in biological life. It consists of glyoxalase 1 (GLO1), glyoxalase 2 (GLO2), and reduced glutathione (GSH), which perform an essential metabolic function in cells by detoxifying methylglyoxal (MG) and other endogenous harmful metabolites into non-toxic d-lactate. MG and MG-derived advanced glycation endproducts (AGEs) are associated with various diseases, such as diabetes, cardiovascular disease, neurodegenerative disorders and cancer, and GLO1 is a key rate-limiting enzyme in the anti-glycation defense. The abnormal activity and expression of GLO1 in various diseases make this enzyme a promising target for drug design and development. This review focuses on the regulatory mechanism of GLO1 in diverse pathogenic conditions with a thorough discussion of GLO1 regulators since their discovery, including GLO1 activators and inhibitors. The different classes, chemical structure and structure-activity relationship are embraced. Moreover, assays for the discovery of small molecule regulators of the glyoxalase system are also introduced in this article. Compared with spectrophotometer-based assay, microplate-based assay is a more simple, rapid and quantitative high-throughput method. This review will be useful to design novel and potent GLO1 regulators and hopefully provide a convenient reference for researchers.

A Visual Approach for the SARS (Severe Acute Respiratory Syndrome) Outbreak Data Analysis.

Virus outbreaks are threats to humanity, and coronaviruses are the latest of many epidemics in the last few decades in the world. SARS-CoV (Severe Acute Respiratory Syndrome Associated Coronavirus) is a member of the coronavirus family, so its study is useful for relevant virus data research. In this work, we conduct a proposed approach that is non-medical/clinical, generate graphs from five features of the SARS outbreak data in five countries and regions, and offer insights from a visual analysis perspective. The results show that prevention measures such as quarantine are the most common control policies used, and areas with strict measures did have fewer peak period days; for instance, Hong Kong handled the outbreak better than other areas. Data conflict issues found with this approach are discussed as well. Visual analysis is also proved to be a useful technique to present the SARS outbreak data at this stage; furthermore, we are proceeding to apply a similar methodology with more features to future COVID-19 research from a visual analysis perfective.

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.

Sub-3 nm Rh nanoclusters confined within a metal-organic framework for enhanced hydrogen generation.

Ultrafine sub-3 nm Rh nanoclusters confined within a metal-organic framework (UIO-66) were constructed through a double-solvent host-guest strategy and achieved superior hydrogen generation via ammonia borane hydrolysis compared with Rh nanoclusters dispersed on the exterior walls.

[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.

Design, Synthesis and Biological Evaluation of Potent Human Glyoxalase I Inhibitors.

Several glutathione derivatives bearing the S-(N-aryl-N-hydroxycarbamoyl) or S-(C-aryl-N-hydroxycarbamoyl) moieties (10, 10', 13-15) were synthesized, characterized, and their human glyoxalase I (hGLO1) inhibitory activity was evaluated. Compound 10 was proved to be the effective hGLO1 inhibitor with a Ki value of 1.0 nM and the inhibition effect of compound 10 on hGLO1 was nearly ten-fold higher than that of the strongest inhibitor 2 (Ki=10.0 nM) which has been reported in the field of glutathione-type hGLO1 inhibitors. Its diethyl ester prodrug 10' was able to penetrate cell membrane and had good inhibitory effect on the growth of NCI-H522 cell xenograft tumor model.

[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.