Ursolic acid alleviates meiotic abnormalities induced by 3-nitropropionic acid in mouse oocytes.

3-nitropropionic acid (3-NPA), a toxic metabolite produced by mold, is mainly found in moldy sugarcane. 3-NPA inhibits the activity of succinate dehydrogenase that can induce oxidative stress injury in cells, reduce ATP production and induce oxidative stress in mouse ovaries to cause reproductive disorders. Ursolic acid (UA) has a variety of biological activities and is a pentacyclic triterpene compound found in many plants. This experiment aimed to investigate the cytotoxicity of 3-NPA during mouse oocyte in vitro maturation and the protective effects of UA on oocytes challenged with 3-NPA. The results showed that UA could alleviate 3-NPA-induced oocyte meiotic maturation failure. Specifically, 3-NPA induced a decrease in the first polar body extrusion rate of oocytes, abnormal distribution of cortical granules, and an increase in the proportion of spindle abnormalities. In addition, 3-NPA caused mitochondrial dysfunction and induced oxidative stress, including decreases in the GSH, mitochondrial membrane potential and ATP levels, and increases in the ROS levels, and these effects led to apoptosis and autophagy. The addition of UA could significantly improve the adverse effects caused by 3-NPA. In general, our data show that 3-NPA affects the normal development of oocytes during the in vitro culture, and the addition of UA can effectively repair the damage caused by 3-NPA to oocytes.

Isoliquiritin can cause mitochondrial dysfunction and regulate Nrf2 to affect the development of mouse oocytes.

IsoliQuirtigenin (ILG) has been widely studied in somatic cells and tissues, but less in reproductive development. It is a kind of widely used food additive. In this study, it was found that ILG could significantly increase the levels of ROS,GSH and MMP in mouse oocytes (P < 0.01). In order to explore the cause of this phenomenon, it was found that the abnormal distribution of mitochondria and ATP synthesis levels were significantly increased (P < 0.05). At this time, we made a reasonable hypothesis that ILG affected mitochondrial function. In subsequent studies, it was found that the endogenous ROS accumulation level in mitochondria was significantly increased. After continuous RT-PCR screening, it was found that the expression of Nrf2 was significantly inhibited (P < 0.01). Its upstream and downstream FOXO3 GPX1, CAT, SOD2, SIRT1 gene also appear different degree of significant change (P < 0.05), in which the lower expression of NADP + (P < 0.05) illustrates the mitochondrial ATP synthesis electronic chain were suppressed, it also has the reason, By inhibiting electron chain and ATP synthesis, ILG leads to oocyte apoptosis and initiation of autophagy, reducing oocyte and its subsequent developmental potential.

Effects of limonin on oxidative stress and early apoptosis in oocytes during in vitro maturation.

To investigate the effects of limonin (Lim) on oxidative stress and early apoptosis in bovine oocytes during in vitro maturation (IVM), different concentrations of Lim (0, 10, 20, 50 µmol/L) were added to bovine IVM medium. Oocyte maturation rates and development 24 h after in vitro fertilization (IVF) were examined to determine the optimal Lim concentration. The optimal Lim concentration was added to the IVM medium, and 0 µmol/L Lim was used as the control. Immunofluorescence staining was used to detect the abnormal rate of spindle assembly, reactive oxygen species (ROS), glutathione (GSH), mitochondrial membrane potential (MMP) levels, mitochondrial distribution, and the fluorescence intensity of cathepsin B (CB)-active LC3 protein. RT‒qPCR was used to detect the mRNA expression levels of antioxidant-, apoptosis- and autophagy-related genes in oocytes. The total number of blastocysts and the proportion of apoptotic cells among blastocysts were detected. The results showed that the PBI ejection rate, cleavage rate and blastocyst rate of bovine oocytes in the 20 µmol/L Lim group were significantly higher than those in the control group (P < 0.05). Compared with those in the control group, ROS levels, abnormal mitochondrial distribution, the proportion of abnormal spindle assembly, CB activity and LC3 protein fluorescence intensity of oocytes in the 20 µmol/L Lim group were significantly decreased (P < 0.05), and GSH and MMP levels were significantly increased (P < 0.05). The expression of antioxidant genes (Prdx3, Prdx6, Sirt1) and antiapoptotic genes (Bcl-xl, Survivin) were significantly upregulated (P < 0.05), and the expression levels of proapoptotic genes (Caspase-4, BAX) and autophagy-related genes (LC3) were significantly downregulated (P < 0.05). The total number of cells among in vitro fertilized embryos was significantly increased (P < 0.05), and the apoptosis rate of blastocysts was significantly decreased (P < 0.05). Here, we show that Lim exerts positive effects on bovine oocyte IVM by regulating REDOX homeostasis, reducing spindle damage and enhancing mitochondrial function during IVM, thereby inhibiting oocyte apoptosis and autophagy.

Dendrobine enhances bovine oocyte maturation and subsequent embryonic development and quality.

Strategies for improving the quality of oocytes have important theoretical and practical significance for increasing the efficiency of livestock breeding. In this respect, the accumulation of reactive oxygen species (ROS) is a major factor affecting the development of oocytes and embryos. This study investigated the effects of Dendrobium nobile extract (DNE) on the in vitro maturation of bovine oocytes and embryonic development after IVF. DNE is an extract from Dendrobium rhizomes that contains alkaloids with anti-inflammatory, anti-cancer and anti-ageing functions. Various concentrations of DNE (0, 5, 10, 20 and 50 µmol/L) were added during oocyte maturation in vitro, and we found that 10 µmol/L of DNE remarkably increased the oocyte maturation rate, the subsequent blastocyst formation rate and embryo quality. Further, we found that DNE treatment decreased the frequency of spindle/chromosome defects and ROS and increased the oocyte glutathione and mitochondrial membrane potential in oocytes. Moreover, DNE upregulated the expression of oxidative stress-related genes (Sirt1, Sirt2, Sirt3 and Sod1) in oocytes and apoptosis-related genes (Caspase-3, Caspase-4, Bax, Bcl-xl and Survivin) in blastocysts. These results suggest that DNE supplementation can promote oocyte maturation and subsequent embryonic development by regulating redox reactions and inhibiting embryonic apoptosis.

Comprehensive Analysis and Reinforcement Learning of Hypoxic Genes Based on Four Machine Learning Algorithms for Estimating the Immune Landscape, Clinical Outcomes, and Therapeutic Implications in Patients With Lung Adenocarcinoma.

Background: Patients with lung adenocarcinoma (LUAD) exhibit significant heterogeneity in therapeutic responses and overall survival (OS). In recent years, accumulating research has uncovered the critical roles of hypoxia in a variety of solid tumors, but its role in LUAD is not currently fully elucidated. This study aims to discover novel insights into the mechanistic and therapeutic implications of the hypoxia genes in LUAD cancers by exploring the potential association between hypoxia and LUAD. Methods: Four machine learning approaches were implemented to screen out potential hypoxia-related genes for the prognosis of LUAD based on gene expression profile of LUAD samples obtained from The Cancer Genome Atlas (TCGA), then validated by six cohorts of validation datasets. The risk score derived from the hypoxia-related genes was proven to be an independent factor by using the univariate and multivariate Cox regression analyses and Kaplan-Meier survival analyses. Hypoxia-related mechanisms based on tumor mutational burden (TMB), the immune activity, and therapeutic value were also performed to adequately dig deeper into the clinical value of hypoxia-related genes. Finally, the expression level of hypoxia genes was validated at protein level and clinical samples from LUAD patients at transcript levels. Results: All patients in TCGA and GEO-LUAD group were distinctly stratified into low- and high-risk groups based on the risk score. Survival analyses demonstrated that our risk score could serve as a powerful and independent risk factor for OS, and the nomogram also exhibited high accuracy. LUAD patients in high-risk group presented worse OS, lower TMB, and lower immune activity. We found that the model is highly sensitive to immune features. Moreover, we revealed that the hypoxia-related genes had potential therapeutic value for LUAD patients based on the drug sensitivity and chemotherapeutic response prediction. The protein and gene expression levels of 10 selected hypoxia gene also showed significant difference between LUAD tumors tissues and normal tissues. The validation experiment showed that the gene transcript levels of most of their genes were consistent with the levels of their translated proteins. Conclusions: Our study might contribute to the optimization of risk stratification for survival and personalized management of LUAD patients by using the hypoxia genes, which will provide a valuable resource that will guide both mechanistic and therapeutic implications of the hypoxia genes in LUAD cancers.

Gold Nanostrip Array-Mediated Wireless Electrical Stimulation for Accelerating Functional Neuronal Differentiation.

Neural stem cell (NSC)-based therapy holds great promise for the treatment of neurodegenerative diseases. Presently, however, it is hindered by poor functional neuronal differentiation. Electrical stimulation is considered one of the most effective ways to promote neuronal differentiation of NSCs. In addition to surgically implanted electrodes, traditional electrical stimulation includes wires connected to the external power supply, and an additional surgery is required to remove the electrodes or wires following stimulation, which may cause secondary injuries and infections. Herein, a novel method is reported for generation of wireless electrical signals on an Au nanostrip array by leveraging the effect of electromagnetic induction under a rotating magnetic field. The intensity of the generated electrical signals depends on the rotation speed and magnetic field strength. The Au nanostrip array-mediated electric stimulation promotes NSC differentiation into mature neurons within 5 days, at the mRNA, protein, and function levels. The rate of differentiation is faster by at least 5 days than that in cells without treatment. The Au nanostrip array-based wireless device also accelerates neuronal differentiation of NSCs in vivo. The novel method to accelerate the neuronal differentiation of NSCs has the advantages of wireless, timely, localized and precise controllability, and noninvasive power supplementation.

E-waste dismantling-related occupational and routine exposure to melamine and its derivatives: Estimating exposure via dust ingestion and hand-to-mouth contact.

Melamine (MEL) and its derivatives are increasingly applied as nitrogenous flame retardants in consumer products. Nevertheless, limited information is available on their environmental occurrence and subsequent human exposure via multiple exposure pathways. In this study, we analysed MEL and its derivatives in dust (indication of the dust ingestion route) and hand wipe samples (indication of the hand-to-mouth route) collected in various microenvironments. The levels of ∑MELs in both dust (median: 24,100 ng/g) and participant hand samples (803 ng/m2) collected in e-waste dismantling workshops were significantly higher than those in samples collected in homes (15,600 ng/g and 196 ng/m2, respectively), dormitories (13,100 ng/g and 227 ng/m2, respectively) and hotel rooms (11,800 ng/g and 154 ng/m2, respectively). Generally, MEL dominated in dust samples collected in e-waste dismantling workshops, whereas cyanuric acid dominated in hand wipe samples. This may occur partly because the latter is an ingredient in disinfection products, which are more frequently employed in daily lives during the COVID-19 pandemic. Exposure assessment suggests that dust ingestion is an important exposure pathway among dismantling workers and the general population, whereas hand-to-mouth contact could not be overlooked in certain populations, such as children and dismantling workers not wear gloves at work.

Hydroxyapatite Nanorods Function as Safe and Effective Growth Factors Regulating Neural Differentiation and Neuron Development.

Neural stem cell (NSC) transplantation is one of the most promising therapeutic strategies for neurodegenerative diseases. However, the slow spontaneous differentiation of NSCs often hampers their application in neural repair. Although some biological growth factors accelerate the differentiation of NSCs, their high cost, short half-life, and unpredictable behavior in vivo, as well as the complexity of the operation, hinder their clinical use. In this study, it is demonstrated that hydroxyapatite (HAp), the main component of bone, in the form of nanorods, can regulate the neural differentiation of NSCs and maturation of the newly differentiated cells. Culturing NSCs with HAp nanorods leads to the differentiation of NSCs into mature neurons that exhibit well-defined electrophysiological behavior within 5 days. The state of these neurons is much better than when culturing the cells without HAp nanorods, which undergo a 2-week differentiation process. Furthermore, RNA-sequencing data reveal that the neuroactive ligand-receptor interaction pathway is dominant in the enriched differentiated neuronal population. Hence, inorganic growth factors like HAp act as a feasible, effective, safe, and practical tool for regulating the differentiation of NSCs and can potentially be used in the treatment of neurodegenerative diseases.

Effects of natural organic matter on cadmium mobility in paddy soil: A review.

Cadmium (Cd) contamination in paddy soil has caused public concern. The uptake of Cd by rice plants depends on soil Cd mobility, which is in turn substantially influenced by organic matter (OM). In this review, we first summarize the fate of Cd in soil and the role of OM. We then focus on the effects of OM on Cd mobility in paddy soil and the factors influencing the remedial effectiveness of OM amendments. We further discuss the performance of straw incorporation in the remediation of Cd-contaminated paddy soils reported in laboratory and field studies. Considering the huge production of organic materials (such as straw) in agriculture, the use of natural OM for soil remediation has obvious appeal due to the environmental benefits and low cost. Although there have been successful application cases, the properties of OM amendments and soil can significantly affect the remedial performance of the OM amendments. Importantly, straw incorporation alone does not often decrease the mobility of Cd in soil or the Cd content in rice grains. Careful evaluation is required when considering natural OM amendments, and the factors and mechanisms that influence their remedial effectiveness need further investigation in paddy soil with realistic Cd concentrations.

Genomic population structure of Helicobacter pylori Shanghai isolates and identification of genomic features uniquely linked with pathogenicity.

Severe Helicobacter pylori-linked gastric disorders are especially prevalent in the East Asia region. The ability of H. pylori to cause different clinical outcomes is thought to be associated with unique sets of its genetic features. However, only few genetic features have been definitively linked to specific gastrointestinal pathologies. Genome heterogeneity of clinical H. pylori strains from patients with four different gastric disorders was studied to explore the population structure and molecular genomic features and their association with pathogenicity. Population analysis showed that 92.9% of the Shanghai H. pylori isolates were clustered in the East Asia group. Among 2,866 genes detected in all genomes, 1,146 genes formed the core genome, whereas 209 unique genes were detected in individual disease groups. The unique genes of peptic ulcer and gastric cancer groups represented the inorganic ion transport and metabolism function gene clusters. Sixteen virulence genes were detected with statistically different detection rates among the four disease groups. Furthermore, 127 clustered regularly interspaced short palindromic repeats were found with significantly different rates in the four disease groups. A total of 337 putative genomic islands were identified, and three genomic islands were individually found in more than 10% of strains. The genomic islands included several metabolism-associated genes and many genes with unknown function. In total, 88 sequence types were detected among the 112 Shanghai H. pylori isolates. Our study provides an essential milestone in the mapping of specific genomic features and their functions to identify factors needed to induce specific gastric disorders in H. pylori.

Interleukin-4 assisted calcium-strontium-zinc-phosphate coating induces controllable macrophage polarization and promotes osseointegration on titanium implant.

Titanium (Ti) and its alloys are believed to be promising scaffold materials for dental and orthopedic implantation due to their ideal mechanical properties and biocompatibility. However, the host immune response always causes implant failures in the clinic. Surface modification of the Ti scaffold is an important factor in this process and has been widely studied to regulate the host immune response and to further promote bone regeneration. In this study, a calcium-strontium-zinc-phosphate (CSZP) coating was fabricated on a Ti implant surface by phosphate chemical conversion (PCC) technique, which modified the surface topography and element constituents. Here, we envisioned an accurate immunomodulation strategy via delivery of interleukin (IL)-4 to promote CSZP-mediated bone regeneration. IL-4 (0 and 40 ng/mL) was used to regulate immune response of macrophages. The mechanical properties, biocompatibility, osteogenesis, and anti-inflammatory properties were evaluated. The results showed that the CSZP coating exhibited a significant enhancement in surface roughness and hydrophilicity, but no obvious changes in proliferation or apoptosis of bone marrow mesenchymal stem cells (BMMSCs) and macrophages. In vitro, the mRNA and protein expression of osteogenic related factors in BMMSCs cultured on a CSZP coating, such as ALP and OCN, were significantly higher than those on bare Ti. In vivo, there was no enhanced bone formation but increased macrophage type 1 (M1) polarization on the CSZP coating. IL-4 could induce M2 polarization and promote osteogenesis of BMMSCs on CSZP in vivo and in vitro. In conclusion, the CSZP coating is an effective scaffold for BMMSCs osteogenesis, and IL-4 presents the additional advantage of modulating the immune response for bone regeneration on the CSZP coating in vivo.

Acidic pH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike.

Lassa virus is an enveloped, bi-segmented RNA virus and the most prevalent and fatal of all Old World arenaviruses. Virus entry into the host cell is mediated by a tripartite surface spike complex, which is composed of two viral glycoprotein subunits, GP1 and GP2, and the stable signal peptide. Of these, GP1 binds to cellular receptors and GP2 catalyzes fusion between the viral envelope and the host cell membrane during endocytosis. The molecular structure of the spike and conformational rearrangements induced by low pH, prior to fusion, remain poorly understood. Here, we analyzed the three-dimensional ultrastructure of Lassa virus using electron cryotomography. Sub-tomogram averaging yielded a structure of the glycoprotein spike at 14-Å resolution. The spikes are trimeric, cover the virion envelope, and connect to the underlying matrix. Structural changes to the spike, following acidification, support a viral entry mechanism dependent on binding to the lysosome-resident receptor LAMP1 and further dissociation of the membrane-distal GP1 subunits.

Introduction of ß-cyclodextrin into poly(aspartic acid) matrix for adsorption and time-release of ibuprofen.

Biodegradable copolymers with molecule inclusion ability was prepared by introduction of ß-cyclodextrin into poly(aspartic acid) matrices. The ibuprofen loading and dissolution properties of poly(aspartic acid)-ß-cyclodextrin were investigated.