AZIN2 is associated with apoptosis of germ cells in undescended testis.

Undescended testis (UDT), known as cryptorchidism (CRY), is a common congenital disorder in which one or both testicles do not descend normally into the scrotum. A unilateral UDT model was established by inducing UDT in mice through surgery. The results showed that the testis in the UDT model group was abnormal; the lumen of the seminiferous tubule was atrophic; apoptosis, necrosis and shedding were observed in many of the germ cells; the level of sex hormones was abnormal; and mature sperm was reduced. Subsequently, transcriptome sequencing was conducted on the testicular tissue of UDT model mice. Through analysis and verification of differential genes, AZIN2 was identified as playing a key role in the decline in male fertility caused by cryptorchidism. AZIN2 expression and spermine content was down-regulated in the testis of the UDT group. We then used a combination of hypoxanthine and xanthine to create a GC-1 cell damage model. In this model, AZIN2 expression and spermine content was down-regulated. When si-Azin2 transfected GC-1 cells, cell viability and proliferation were decreased. However, in the GC-1 cell damage model transfected with Azin2 over-expressed plasmid, AZIN2 expression and spermine content was up-regulated, reversing the cell damage caused by hypoxanthine and xanthine, and restoring the proliferation ability of GC-1 cells. These results indicate that in UDT, down-regulated AZIN2 expression is a factor in testicular damage. This discussion of the connection between AZIN2 and germ cells has important clinical significance as it provides an important reference for the diagnosis and treatment of cryptorchidism.

(Ca0.25La0.5Dy0.25)CrO3 Ceramic Fiber@Biomass-Derived Carbon Aerogel with Enhanced Solute Transport Channels for Highly Efficient Solar Interface Evaporation.

The use of solar interface evaporation for seawater desalination or sewage treatment is an environmentally friendly and sustainable approach; however, achieving efficient solar energy utilization and ensuring the long-term stability of the evaporation devices are two major challenges for practical application. To address these issues, we developed a novel ceramic fiber@bioderived carbon composite aerogel with a continuous through-hole structure via electrospinning and freeze-casting methods. Specifically, an aerogel was prepared by incorporating perovskite oxide (Ca0.25La0.5Dy0.25)CrO3 ceramic fibers (CCFs) and amylopectin-derived carbon (ADC). The CCFs exhibited remarkable photothermal conversion efficiencies, and the ADC served as a connecting agent and imparted hydrophilicity to the aerogel due to its abundant oxygen-containing functional groups. After optimizing the composition and microstructure, the (Ca0.25La0.5Dy0.25)CrO3 ceramic fiber@biomass-derived carbon aerogel demonstrated remarkable properties, including efficient light absorption and rapid transport of water and solutes. Under 1 kW m-2 light intensity irradiation, this novel material exhibited a high temperature (48.3 °C), high evaporation rate (1.68 kg m-2 h-1), and impressive solar vapor conversion efficiency (91.6%). Moreover, it exhibited long-term stability in water evaporation even with highly concentrated salt solutions (25 wt%). Therefore, the (Ca0.25La0.5Dy0.25)CrO3 ceramic fiber@biomass-derived carbon aerogel holds great promise for various applications of solar interface evaporation.

Medium- and High-Entropy Rare Earth Hexaborides with Enhanced Solar Energy Absorption and Infrared Emissivity.

The development of a new generation of solid particle solar receivers (SPSRs) with high solar absorptivity (0.28-2.5 µm) and high infrared emissivity (1-22 µm) is crucial and has attracted much attention for the attainment of the goals of "peak carbon" and "carbon neutrality". To achieve the modulation of infrared emission and solar absorptivity, two types of medium- and high-entropy rare-earth hexaboride (ME/HEREB6) ceramics, (La0.25Sm0.25Ce0.25Eu0.25)B6 (MEREB6) and (La0.2Sm0.2Ce0.2Eu0.2Ba0.2)B6 (HEREB6), with severe lattice distortions were synthesized using a high-temperature solid-phase method. Compared to single-phase lanthanum hexaboride (LaB6), HEREB6 ceramics show an increase in solar absorptivity from 54.06% to 87.75% in the range of 0.28-2.5 µm and an increase in infrared emissivity from 76.19% to 89.96% in the 1-22 µm wavelength range. On the one hand, decreasing the free electron concentration and the plasma frequency reduces the reflection and ultimately increases the solar absorptivity. On the other hand, the lattice distortion induces changes in the B-B bond length, leading to significant changes in the Raman scattering spectrum, which affects the damping constant and ultimately increases the infrared emissivity. In conclusion, the multicomponent design can effectively improve the solar energy absorption and heat transfer capacity of ME/HEREB6, thus providing a new avenue for the development of solid particles.

Effect of short-term moderate intake of ice wine on hepatic glycolipid metabolism in C57BL/6J mice.

As the correlation between high fructose intake and metabolism-related diseases (e.g., obesity, fatty liver, and type 2 diabetes) has been increasingly reported, the health benefits of consuming ice wine high in fructose have been called into question. In this study, 6-week-old male C57BL/6J mice were divided into control (pure water), fructose (130 g L-1 fructose solution), alcohol (11% alcohol solution), low-dose (50% diluted ice wine) and high-dose ice wine (100% ice wine) groups to investigate the effects and mechanisms of short-term (4 weeks) ice wine intake on hepatic glycolipid metabolism in mice. The results showed that short-term consumption of ice wine suppressed the elevation of low-density lipoprotein cholesterol content and did not cause hepatic lipid accumulation compared with those of the fructose group. Meanwhile, ice wine had no significant effect on lipogenesis although it inhibited fatty acid oxidation via the PPARα/CPT-1α pathway. Compared with the control group, ice wine interfered with the elevation of fasting glucose and the insulin resistance index in a dose-dependent manner, and led to an increase in plasma uric acid levels, which may further contribute to the disruption of glucolipid metabolism. Overall, short-term moderate intake of ice wine over a 4-week period may not significantly affect hepatic glycolipid metabolism in C57BL/6J mice for the time being.

Bisphenol A triggers apoptosis in mouse pre-antral follicle granulosa cells via oxidative stress.

BACKGROUND: Bisphenol A (BPA), an endocrine disrupting chemical with weak estrogenic and anti-androgenic activity, is widely present in various environmental media and organisms. It has certain reproductive toxicity and can cause a variety of female reproductive system diseases. Although BPA-stimulated apoptosis of granulosa cells has been widely elaborated, the effect of BPA on mouse pre-antral follicle granulosa cells (mpGCs) has not been well elucidated. RESULTS: In this study, the results of live-dead cell staining showed that high concentrations of BPA severely impaired mpGCs growth viability and affected the cell cycle transition of mpGCs. We confirmed that BPA promotes the production of reactive oxygen species (ROS) and facilitates oxidative stress in mpGCs. In addition, immunofluorescence, transmission electron microscopy, and flow cytometry experiments demonstrated that BPA treatment for mpGCs resulted in apoptotic features, such as rounding, cytoplasmic crinkling, and mitochondrial damage. This was accompanied by a large production of ROS and apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. RNA-seq data showed that several apoptosis-related pathways were enriched in the high concentration BPA-treated group compared with the normal group, such as the p53 pathway, MAPK pathway, etc. CONCLUSIONS: These results suggest that cells undergo oxidative stress effects and apoptosis after BPA treatment for mpGCs, which affects normal follicle development. The potential mechanism of BPA-induced female reproductive toxicity was elucidated, while providing a research basis for the prevention and treatment of female reproductive diseases.

A covalent organic framework-derived M1 macrophage mimic nanozyme for precise tumor-targeted imaging and NIR-II photothermal catalytic chemotherapy.

Nanoprobes for efficient tumor-targeted imaging and therapy are urgently needed for clinical tumor theranostics. Herein, inspired by the heterogeneity of the tumor microenvironment, we report a covalent organic framework (COF)-derived biomimetic nanozyme for precise tumor-targeted imaging and NIR-II photothermal-catalysis-enhanced chemotherapy (PTCEC). Using a crystalline nanoscale COF as the precursor, a peroxidase-like porous N-doped carbonous nanozyme (PNC) was obtained, which was cloaked with an M1 macrophage cell membrane (M1m) to create a multifunctional biomimetic nanoprobe for tumor-targeted imaging and therapy. The M1m coating enabled the nanoprobe to target cancer cells and tumor tissues for highly efficient tumor imaging and drug delivery. The peroxidase-like activity of the PNC allowed for the conversion of intratumoral H2O2 into toxic ˙OH that synergized with its NIR-II photothermal effect to strengthen the chemotherapy. Therefore, highly efficient tumor-targeted imaging and NIR-II PTCEC were realized with an M1 macrophage mimic nanoprobe. This work provides a feasible tactic for a biomimetic theranostic nanoprobe and will inspire the development of new bioactive nanomaterials for clinical tumor theranostic applications.

Stimuli-responsive probes for amplification-based imaging of miRNAs in living cells.

MicroRNAs (miRNAs) have emerged as important biomarkers in biomedicine and bioimaging due to their roles in various physiological and pathological processes. Real-time and in situ monitoring of dynamic fluctuation of miRNAs in living cells is crucial for understanding these processes. However, current miRNA imaging probes still have some limitations, including the lack of effective amplification methods for low abundance miRNAs bioanalysis and uncontrollable activation, leading to background signals and potential false-positive results. Therefore, researchers have been integrating activatable devices with miRNA amplification techniques to design stimuli-responsive nanoprobes for "on-demand" and precise imaging of miRNAs in living cells. In this review, we summarize recent advances of stimuli-responsive probes for the amplification-based imaging of miRNAs in living cells and discuss the future challenges and opportunities in this field, aiming to provide valuable insights for accurate disease diagnosis and monitoring.

Metal-Organic Framework-Derived Multifunctional Nucleic Acid Nanoprobes for Hypoxia Imaging-Guided Radiosensitization.

The efficacy of radiotherapy (RT) is usually restricted by the hypoxic microenvironment and the poor radiation attenuation coefficient of tumor tissue. Theranostic probes that simultaneously evaluate the hypoxia degree and sensitize cancer cells toward RT are promising for improving the treatment efficacy and avoiding overtreatment. We rationally designed a metal-organic framework (MOF)-derived multifunctional nanoprobe for hypoxia imaging-guided radiosensitization. Hf-MOF was carbonized to obtain a porous carbonous nanostructure containing ultrasmall HfO2 (HfC); then, a fluorophore-labeled HIF-α mRNA antisense sequence was readily adsorbed and quenched by HfC to obtain the nanoprobe (termed HfC-Hy). The antisense sequence could easily hybridize with HIF-α mRNA and recover its fluorescence signal to evaluate the degree of hypoxia, while the HfC nanostructure could deposit more radiation energy in cancer cells for radiosensitization. A series of in vitro and in vivo experiments demonstrated that the nanoprobe could be successfully utilized for imaging the hypoxic degree of cancer cells/tumor tissue and guiding radiosensitization. This work not only developed a highly efficient and safe nanosensitizer but also offered a potential solution for customized clinical RT.

Effect of Low Dietary Folate on Mouse Spermatogenesis and Spindle Assembly Checkpoint Dysfunction May Contribute to Folate Deficiency-Induced Chromosomal Instability in Cultured Mouse Spermatogonia.

Folate, as the initial substrate in one-carbon metabolism, is involved in the synthesis of important substances such as DNA, RNA, and protein. Folate deficiency (FD) is associated with male subfertility and impaired spermatogenesis, yet the underlying mechanisms are poorly understood. In the present study, we established an animal model of FD to investigate the effect of FD on spermatogenesis. GC-1 spermatogonia were used as a model to investigate the effect of FD on proliferation, viability, and chromosomal instability (CIN). Furthermore, we explored the expression of core genes and proteins of spindle assembly checkpoint (SAC), a signaling cascade ensuring accurate chromosome segregation and preventing CIN during mitosis. Cells were maintained in medium containing 0, 20, 200, or 2000 nM folate for 14 days. CIN was measured by using a cytokinesis-blocked micronucleus cytome assay. We found that sperm counts decreased significantly (p < 0.001) and the rate of sperm with defects in the head increased significantly (p < 0.05) in FD diet mice. We also found, relative to the folate-sufficient conditions (2000 nM), cells cultured with 0, 20, or 200 nM folate exhibited delayed growth and increased apoptosis in an inverse dose-dependent manner. FD (0, 20, or 200 nM) significantly induced CIN (p < 0.001, p < 0.001, and p < 0.05, respectively). Moreover, FD significantly and inverse dose dependently increased the mRNA and protein expression of several key SAC-related genes. The results indicate that FD impairs SAC activity, which contributes to mitotic aberrations and CIN. These findings establish a novel association between FD and SAC dysfunction. Thus, FD-impaired spermatogenesis may be partly due to genomic instability and proliferation inhibition of spermatogonia.

A gold nanoparticle engineered metal-organic framework nanoreactor for combined ferroptosis and mild photothermal therapy.

We demonstrate a gold nanoparticle engineered metal-organic framework nanoreactor with photothermal, glucose oxidase-like and GSH-consuming performance to achieve the accumulation of hydroxyl radicals and the enhancement of the thermal sensitivity for combined ferroptosis and mild photothermal therapy.

Tumor-targeted nanoflowers regulate glutamine metabolism and amplify oxidative stress for synergistic therapy.

We designed and synthesized tumor-targeted nanoflowers to inhibit glutamine metabolism and amplify oxidative stress, which could synergistically suppress tumor growth.

Targeted Imaging in Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease involved in plaque rupture, stroke, thrombosis, and heart attack (myocardial infarction), which is a leading cause of sudden cardiovascular events. In the past decades, various imaging strategies have been designed and employed for the diagnosis of atherosclerosis. Targeted imaging can accurately distinguish pathological tissues from normal tissues and reliably reveal biological information in the occurrence and development of atherosclerosis. By taking advantage of versatile imaging techniques, rationally designed imaging probes targeting biomarkers overexpressed in plaque microenvironments and targeting activated cells by modifying specific ligands accumulated in lesion regions have attracted increasing attention. This Perspective elucidates comprehensively the targeted imaging strategies, current challenges, and future development directions for precise identification and diagnosis of atherosclerosis, which is beneficial to better understand the physiological and pathological progression and exploit novel imaging strategies.

Correlation of Inpatients Suffering from Acute Acalculous Cholecystitis during ICU Treatment with Acute Physiology and Chronic Health Evaluation II Score, Duration of Ventilator Use, and Time on Total Parenteral Nutrition.

Objective: To explore the correlation of inpatients suffering from acute acalculous cholecystitis (AAC) during ICU treatment with Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, duration of ventilator use, and time on total parenteral nutrition (TPN). Methods: From March 2016 to March 2022, the clinical data of 47 patients with AAC who received ICU treatment in our hospital were retrospectively reviewed, and these patients were included in the AAC group. Another 36 patients treated in the ICU in the same period with age and gender matching with those in the AAC group were selected as the non-AAC group. Patients' various clinical data were recorded to analyze the correlation of AAC with APACHE-II score, duration of ventilator use, and time on TPN. Results: The shock time, duration of ventilator usage, and duration of sedative medicine use were all substantially longer in the AAC group than in the non-AAC group, according to the univariate analysis (P < 0.05); the amount of norepinephrine used, white blood cell count, C-reactive protein (CRP) amount, and APACHE-II score were significantly higher in the AAC group than in the non-AAC group (P < 0.05); between the two groups, the time on TPN and fasting time were different, but with no statistical significance (P > 0.05); after performing Spearman's correlation with the significantly between-group different indicators, the result showed that the amount of norepinephrine used, duration of ventilator use, white blood cell count, and CRP amount were significantly correlated with the occurrence of AAC, and the correlation was positive (P all <0.001). Conclusion: The APACHE-II score and time on TPN are not significantly correlated with the occurrence of AAC; and the amount of norepinephrine used, duration of ventilator use, white blood cell count, and serum CRP are positively correlated with the occurrence of AAC. Measuring the variations in the levels of various markers can signal the onset of AAC or reflect the state and prognosis, suggesting a possible application in clinic-based targeted prevention and treatment of AAC.

Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules.

Long noncoding RNAs (lncRNAs) have been demonstrated to regulate reproduction in mammals. Our previous study revealed that the expression level of lncRNA-Gm2044 was obviously elevated in nonobstructive azoospermia with spermatogonial arrest. Here, a transgenic mouse model of lncRNA-Gm2044 in spermatogonia using the Stra8 promoter was constructed to explore the roles of upregulated lncRNA-Gm2044 in male fertility. Testicular morphology and fertility weren't affected in transgenic mice expressing lncRNA-Gm2044. However, overexpression of lncRNA-Gm2044 in spermatogonia partially impaired spermatogenesis in the transgenic mice. Then, transcriptome sequencing was executed to find the potential signaling pathway repressing spermatogenesis in germ cells of lncRNA-Gm2044 transgenic mice. Through quantitative analysis of differentially expressed genes, 442 upregulated mRNAs and 147 downregulated mRNAs were displayed in male germ cells of Gm2044-transgenic mice (Gm2044-Tg) compared with non-transgenic mice (Non-Tg). Using gene ontology (GO) analysis, differentially expressed genes were shown to play vital roles in RNA_metabolic_process, Central_element, Enzyme_binding, and Intracellular_bridge. Using Kyoto encyclopedia of genes and genomes (KEGG) analysis, differentially expressed genes were shown to participate in RNA_transport, Cell_cycle, Renin-angiotensin_system, and Chemokine_signaling_pathway. Gene Set Enrichment Analysis (GSEA) revealed that Acrosome_assembly and Sperm_plasma_membrane were involved in the overexpression of lncRNA-Gm2044 blocking spermatogenesis. Furthermore, some of the most differentially expressed mRNAs were verified by RT-qPCR. In addition, we determined that the lncRNA-Gm2044 has no ability to translate into peptides by the bioinformatics method and molecular experiment. Thus, lncRNA-Gm2044 is a novel molecular target for the diagnosis and treatment of male infertility.

The effects and molecular mechanism of heat stress on spermatogenesis and the mitigation measures.

Under normal conditions, to achieve optimal spermatogenesis, the temperature of the testes should be 2-6 °C lower than body temperature. Cryptorchidism is one of the common pathogenic factors of male infertility. The increase of testicular temperature in male cryptorchidism patients leads to the disorder of body regulation and balance, induces the oxidative stress response of germ cells, destroys the integrity of sperm DNA, yields morphologically abnormal sperm, and leads to excessive apoptosis of germ cells. These physiological changes in the body can reduce sperm fertility and lead to male infertility. This paper describes the factors causing testicular heat stress, including lifestyle and behavioral factors, occupational and environmental factors (external factors), and clinical factors caused by pathological conditions (internal factors). Studies have shown that wearing tight pants or an inappropriate posture when sitting for a long time in daily life, and an increase in ambient temperature caused by different seasons or in different areas, can cause an increase in testicular temperature, induces testicular oxidative stress response, and reduce male fertility. The occurrence of cryptorchidism causes pathological changes within the testis and sperm, such as increased germ cell apoptosis, DNA damage in sperm cells, changes in gene expression, increase in chromosome aneuploidy, and changes in Na+/K+-ATPase activity, etc. At the end of the article, we list some substances that can relieve oxidative stress in tissues, such as trigonelline, melatonin, R. apetalus, and angelica powder. These substances can protect testicular tissue and relieve the damage caused by excessive oxidative stress.

Role of Oxidative Stress in Varicocele.

According to the official statistics of the World Health Organization, at least 48 million couples and 186 million people suffer from infertility. Varicocele has been recognized as the leading cause of male infertility and can affect spermatogenesis and cause testicular and epididymal disorders through multiple diverse pathophysiological processes. Reactive oxygen species (ROS) produced by oxidative stress have been reconciled as an important pathogenic factor throughout the course of varicocele. Testis respond to heat stress, hypoxia, and inflammation at the cost of producing excessive ROS. High levels of ROS can lead to infertility not only through lipid peroxidation or DNA damage, but also by inactivating enzymes and proteins in spermatogenesis. This review studies the oxidative stress and its role in the pathophysiology and molecular biology of varicocele in the context of a decline in fertility.

Roles of Noncoding RNA in Reproduction.

The World Health Organization predicts that infertility will be the third major health threat after cancer and cardiovascular disease, and will become a hot topic in medical research. Studies have shown that epigenetic changes are an important component of gametogenesis and related reproductive diseases. Epigenetic regulation of noncoding RNA (ncRNA) is appropriate and is a research hotspot in the biomedical field; these include long noncoding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA). As vital members of the intracellular gene regulatory network, they affect various life activities of cells. LncRNA functions as a molecular bait, molecular signal and molecular scaffold in the body through molecular guidance. miRNAs are critical regulators of gene expression; they mainly control the stability or translation of their target mRNA after transcription. piRNA functions mainly through silencing genomic transposable elements and the post-transcriptional regulation of mRNAs in animal germ cells. Current studies have shown that these ncRNAs also play significant roles in the reproductive system and are involved in the regulation of essential cellular events in spermatogenesis and follicular development. The abnormal expression of ncRNA is closely linked to testicular germ cell tumors, poly cystic ovary syndrome and other diseases. This paper briefly presents the research on the reproductive process and reproductive diseases involving ncRNAs.