Antitumor Effect of Apcin on Endometrial Carcinoma via p21-Mediated Cell Cycle Arrest and Apoptosis.

OBJECTIVE: Endometrial carcinoma (EC) is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates. This underscores the critical need for novel therapeutic targets. One such potential target is cell division cycle 20 (CDC20), which has been implicated in oncogenesis. This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved. METHODS: The effects of Apcin on EC cell proliferation, apoptosis, and the cell cycle were evaluated using CCK8 assays and flow cytometry. RNA sequencing (RNA-seq) was subsequently conducted to explore the underlying molecular mechanism, and Western blotting and coimmunoprecipitation were subsequently performed to validate the results. Animal studies were performed to evaluate the antitumor effects in vivo. Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC. RESULTS: Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells, resulting in cell cycle arrest. Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin. Notably, Apcin treatment led to the upregulation of the cell cycle regulator p21, which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells. In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth. Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue, and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval. CONCLUSION: CDC20 is a novel molecular target in EC, and Apcin could be developed as a candidate antitumor drug for EC treatment.

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain.

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation, axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation, differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion.

BACKGROUND: Impaired glucose tolerance (IGT) is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes. When IGT occurs, insulin sensitivity decreases, causing a reduction in insulin secretion and an increase in glucagon secretion. Recently, vascular endothelial growth factor B (VEGFB) has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity. Therefore, we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion, thus contributing to the prevention and cure of prediabetes. AIM: To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT. METHODS: We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression. Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay, and the protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) was determined using western blot. Further, mRNA expression of forkhead box protein O1, phosphoenolpyruvate carboxykinase, and glucose-6 phosphatase was detected via quantitative polymerase chain reaction, and the correlation between the expression of proteins was analyzed via bioinformatics. RESULTS: In mice with IGT and VEGFB knockout, glucagon secretion increased, and the protein expression of PI3K/AKT decreased dramatically. Further, in mice with VEGFB overexpression, glucagon levels declined, with the activation of the PI3K/AKT signaling pathway. CONCLUSION: VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

Biotransformation and bioaccessibility of active ingredients from Radix Astragali by Poria cocos during solid-state fermentation and in vitro digestion and antioxidant activity evaluation.

Radix Astragali is one of the most famous and frequently used health food supplements and herbal medicines. Among more than 227 components of Radix Astragali, Astragaloside IV (AG IV) is famous functional compound and is commonly used as a quality marker for Radix Astragali. However, the relatively low content of AG IV in Radix Astragali (< 0.04%, w/w) severely limits its application. The purpose of this study is to improve the biotransformation of AG IV and its bioaccessibility during in vitro digestion by Poria cocos solid fermenting Radix Astragali. The optimum fermentation conditions were as follows: Inoculation amount 8 mL; fermentation time 10 d; fermentation humidity 90%. Through fermentation, the content of AG IV was increased from 384.73 to 1986.49 µg/g by 5.16-fold. After in vitro digestion, the contents of genistin, calycosin, formononetin, AG IV, Astragaloside II (AG II) and total flavonoids in fermented Radix Astragali (FRA) of enteric phase II (ENTII) were 34.52 µg/g, 207.32 µg/g, 56.76 µg/g, 2331.46 µg/g, 788.31 µg/g, 3.37 mg/g, which were 2.08-fold, 2.51-fold, 1.05-fold, 8.62-fold, 3.22-fold and 1.50-fold higher than those of control, respectively. The Scanning electron microscopy (SEM) of FRA showed rough surface and porous structure. The DPPH and ABTS radical scavenging rate of FRA were higher than those of control. These results showed that the Poria cocos solid fermentation could increase the content of the AG IV in Radix Astragali and improve the bioaccessibility and antioxidant activity of Radix Astragali, which is providing new ideas for future development and utilization of Radix Astragali.

Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis.

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

Miniature optoelectronic compound eye camera.

Inspired by insect compound eyes (CEs) that feature unique optical schemes for imaging, there has recently been growing interest in developing optoelectronic CE cameras with comparable size and functions. However, considering the mismatch between the complex 3D configuration of CEs and the planar nature of available imaging sensors, it is currently challenging to reach this end. Here, we report a paradigm in miniature optoelectronic integrated CE camera by manufacturing polymer CEs with 19~160 logarithmic profile ommatidia via femtosecond laser two-photon polymerization. In contrast to µ-CEs with spherical ommatidia that suffer from defocusing problems, the as-obtained µ-CEs with logarithmic ommatidia permit direct integration with a commercial CMOS detector, because the depth-of-field and focus range of all the logarithmic ommatidia are significantly increased. The optoelectronic integrated µ-CE camera enables large field-of-view imaging (90°), spatial position identification and sensitive trajectory monitoring of moving targets. Moreover, the miniature µ-CE camera can be integrated with a microfluidic chip and serves as an on-chip camera for real-time microorganisms monitoring. The insect-scale optoelectronic µ-CE camera provides a practical route for integrating well-developed planar imaging sensors with complex micro-optics elements, holding great promise for cutting-edge applications in endoscopy and robot vision.

The effects of dimethylformamide exposure on liver and kidney function in the elderly population: A cross-sectional study.

Dimethylformamide (DMF) is widely used as a solvent in the production of synthetic leather. Previous studies have focused on workers exposed to DMF in leather factories; however, little attention has been paid to the general population. This study was conducted to examine the effects of DMF exposure on elderly residents living near synthetic leather factories. A total of 962 subjects over 60 years of age in proximity to these factories (monitoring points) were enrolled as the exposure group, and 1924 permanent residents living distant from the factories were enrolled as the control group. The exposure group was divided into 3 groups according to their distance from the monitoring points. Physical examination, routine blood tests, and liver and renal function data were collected, and the DMF concentration in the air was analyzed by gas chromatography-mass spectroscopy. The prevalence of abnormal heart rhythm, electrocardiogram and B-mode ultrasound results in the exposure group was significantly greater than in the control group. Aspartate transaminase (AST), alanine transaminase (ALT), and blood urea nitrogen (BUN) levels in the exposure group also were higher than those in the control group (P < .01). There was an effect of distance from leather factories on liver and kidney dysfunction in the 3 exposure groups. Compared with the exposure group at >3 km distance from the source, the prevalence of increased AST, ALT, and BUN in the exposure group at <1 km was significantly greater (P < .001). It was concluded that DMF exposure was related to an increased risk of a cardiac injury and liver and kidney dysfunction.

Long focusing range and self-healing Bessel vortex beam generator: publisher's note.

This publisher's note contains corrections to Opt. Lett.45, 2580 (2020).OPLEDP0146-959210.1364/OL.391232.

Long focusing range and self-healing Bessel vortex beam generator.

Here a continuous axial-spiral phase microplate (CAsPP), based on combining a logarithmic axicon and a spiral phase plate, was proposed for generating high-quality higher-order Bessel vortex beams. The novel optical component implemented via femtosecond laser direct writing possesses compact geometry and unique optical properties. The CAsPP with a diameter of 80 µm possesses a controllable long focus ranging from 50 to 600 µm and exhibits a good self-healing ability after free transmission of about 45 µm. Unique optical properties were demonstrated in both experiments and simulations, which were well matched to each other. This Letter provides new opportunities for applications in integrated optics, optical trapping, laser machining, and information reconstruction.

Diamond optical vortex generator processed by ultraviolet femtosecond laser.

We propose a precise diamond micromachining method based on ultraviolet femtosecond laser direct writing and a mixed acid heating chemical treatment. The chemical composition of the attached clusters generated during laser ablation and their effects on morphologies were investigated in experiments. The averaged roughness of pristine and processed regions reduced to 0.64 nm and 9.4 nm from 20.5 nm and 37.4 nm, respectively. With this method, spiral zone plates (SZPs) were inscribed on a high-pressure high-temperature diamond surface as micro-optical vortex generators. The optical performances of the diamond SZPs were characterized in both experiments and simulations, which were very consistent with each other. This chemical auxiliary processing method will contribute greatly to the wide application of integration and miniaturization of diamond surface optical components.

Prokineticin 2 overexpression induces spermatocyte apoptosis in varicocele in rats.

Varicocele is one of the most important causes of male infertility, as this condition leads to a decline in sperm quality. It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels, leading to oxidative stress and sperm apoptosis; however, the specific pathogenic mechanisms affecting spermatogenesis remain elusive. Prokineticin 2 (PK2), a secretory protein, is associated with multiple biological processes, including cell migration, proliferation, and apoptosis. In the testis, PK2 is expressed in spermatocytes under normal physiological conditions. To investigate the role of PK2 in varicocele, a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor, prokineticin receptor 1 (PKR1), by immunohistochemistry and quantitative real-time PCR assays (qPCR). Moreover, H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line (GC-2) in vitro, and the apoptosis rate was detected by flow cytometry. Here, we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model. Administration of H2O2 stimulated the overexpression of PK2 in GC-2. Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3, caspase-8, and B cell lymphoma 2-associated X; downregulating B cell lymphoma 2; and promoting the accumulation of intracellular calcium. Overall, we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2, leading to apoptosis of spermatocytes. Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.

Evaluation of the association between urinary cadmium levels below threshold limits and the risk of diabetes mellitus: a dose-response meta-analysis.

As cadmium levels are increasing in the environment, the adverse effects of cadmium exposure specifically associated with chronic diseases are receiving increasing attention. Several population-based studies have been conducted on the association between cadmium and diabetes mellitus (DM) but have reported controversial results. Here, we aimed to evaluate the association between cadmium exposure and DM. In this meta-analysis, a random effects model was used because there was evidence of heterogeneity among studies. A dose-response relationship was assessed through a restricted cubic spline model with three knots. The results showed a positive association between cadmium levels in the body and DM (OR = 1.27; 95% CI, 1.07-1.52). The cadmium levels in the body were defined on the basis of combined urinary and blood cadmium. Subgroup analysis further indicated a positive association between urinary cadmium levels and DM (OR = 1.31; 95% CI, 1.02-1.69). The dose-response analysis results showed a positive association between levels of urinary cadmium above 2.43 µg/g creatinine and DM, and the risk of DM increased by 16% for each l µg/g creatinine increase in urinary cadmium levels. The results from our meta-analysis indicate that cadmium levels in the body are positively associated with DM, and urinary cadmium levels above 2.43 µg/g creatinine are associated with an increased risk of DM.

Effects of forage source and particle size on chewing activity, ruminal pH, and saliva secretion in lactating Holstein cows.

The present study investigated the effects of dietary forage source (quality) and particle size on chewing activity, saliva secretion, and ruminal pH. Twelve multiparous lactating Holstein cows, four of which were ruminally cannulated, were used in a replicated 4 × 4 Latin square experimental design with a 2 × 2 factorial arrangement of treatments. Cows fed wild-rye hay diets had longer daily eating times than cows fed oaten hay diets. Treatments had no effect on ruminating time; therefore, resting time varied inversely to eating time. Neither the rate nor the amount of saliva secretion while eating, ruminating, or resting was affected by diet, resulting in similar total daily saliva secretions across treatments (231 L/day). Total volatile fatty acids (VFAs) in the ruminal fluid from animals fed oaten hay diets were higher than those from animals fed wild-rye hay diets; further, VFAs increased with decreasing forage particle size (FPS). Consistent with elevated VFA concentrations, reducing FPS and including oaten hay in the diet decreased mean ruminal pH and increased the daily time of ruminal pH under 5.8. Results of this study suggest that forage source and particle size affect ruminal pH might be via variations in VFA production rather than increased salivary recycling of buffering substrates.

Genome-wide screening and analysis of imprinted genes in rapeseed (Brassica napus L.) endosperm.

Species-specific genomic imprinting is an epigenetic phenomenon leading to parent-of-origin-specific differential expression of maternally and paternally inherited alleles. To date, no studies of imprinting have been reported in rapeseed, a tetraploid species. Here, we analysed global patterns of allelic gene expression in developing rapeseed endosperms from reciprocal crosses between inbred lines YN171 and 93275. A total of 183 imprinted genes, consisting of 167 maternal expressed genes (MEGs) and 16 paternal expressed genes (PEGs), were identified from 14,394 genes found to harbour diagnostic SNPs between the parental lines. Some imprinted genes were validated in different endosperm stages and other parental combinations by RT-PCR analysis. A clear clustering of imprinted genes throughout the rapeseed genome was identified, which was different from most other plants. Methylation analysis of 104 out of the 183 imprinted genes showed that 11 genes (7 MEGs and 4 PEGs) harboured differentially methylated regions (DMRs). Unexpectedly, only 1 MEG out of these 11 genes had a DMR that exhibited high CG methylation rate in paternal allele and had big difference between parent alleles. These results extend our understanding of gene imprinting in plants and provide potential avenues for further research in imprinted genes.

Synthesis and Application of Water-Soluble Oxazine Dyes for Detection of PHAs-Producing Bacteria.

Derivatives of oxazine dyes were synthesized on mulitigram scales via efficient synthetic strategies. One practical route was selected to prepare compounds 6, 9 and 10, especially water-soluble compound 6 was obtained in better yield than reported, and compound 10 was insoluble in aqueous media in absence of phenolic-OH. Compounds 3 and 9 were found to be clear pH-dependent between pH = 4.0 and 10.0, and could be used as acid-base indicators to measure intracellular pH. Compounds 6, 9, 10 all have carboxylic acid functionalities, which could be activated and used to conjugate the dyes to biomolecules. In addition, compounds 6 and 9 with good solubility in aqueous media were used to develop a simple, quick, safe, highly sensitive staining method to detect PHAs-producing bacteria on heat-fixed smears, which was confirmed by fluorescence images of PHAs granules of bacteria.

Effects of Testosterone Supplementation on Body Composition in HIV Patients: A Meta-analysis of Double-blinded Randomized Controlled Trials.

This study was designed to evaluate the effects of testosterone supplementation (TS) on body composition in patients with HIV and the side effects of TS. A comprehensive literature search strategy was used to retrieve relevant randomized controlled trials (RCTs) examining the effects of TS on body composition. Atotal of 14 eligible studies were included, enrolling 388 and 349 randomized patients in TS and control groups, respectively. The quality of studies included was assessed, and data on total body weight (BW), lean body mass (LBM), fat mass (FM), serum total testosterone (TT), free testosterone (FT) levels, and adverse events were extracted and analyzed using Review Manager software 5.3. Meta-analysis results showed that TS was associated with a small but significant modification in total BW, serum TT, and FT levels in HIV-infected patients and in patients given various drug administrations. TS also significantly increased LBM in male patients, but no significant difference in LBM was observed between female counterparts treated with TS or not. Conversely, TS relative to placebo did not lead to a significant reduction in FM. No significant difference was observed between the two groups in terms of adverse effects. Our findings suggested that TS may be recommended to improve body composition in patients with HIV-related weight loss. However, owing to the high heterogeneity across included trials, further evaluations using large-scale, multi-center, blinded RCTs are needed.

Mirror-rotation-symmetrical single-focus spiral zone plates.

In this Letter, we report mirror-rotation-symmetrical single-focus spiral zone plates (MS-SZPs) fabricated by femtosecond laser direct writing. The novel optical element can generate a single-focus vortex beam, owing to the element's complicated continuous surface. The MS-SZP surface possesses reverse mirror-rotation symmetry, which ensures that the transfer element has the same surface morphology as the original element. Both the transfer element and original element have good optical properties. The single-focus behavior was investigated by a microscopic imaging system and found to be in good agreement with theoretical simulation results. The innovative optical component is expected to be widely used in optical communication, quantum computation, optical manipulation, and other fields.

Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cav1, and Elavl1, and its influence on spermatogenesis.

This study aims to investigate the effect of folate deficiency on the male reproductive function and the underlying mechanism. A total of 269 screened participants from 421 recruitments were enrolled in this study. An animal model of folate deficiency was constructed. Folate concentration was measured in the ejaculate, and its association with semen parameters was then determined. The expression and promoter methylation status of ESR1, CAV1, and ELAVL1 were also evaluated. Results showed that seminal plasma folate level was significantly lower among subjects with azoospermia than those with normozoospermia. Low folate level was significantly correlated with low sperm concentration in men with normozoospermia. Folate deficiency significantly reduced the expression of ESR1, CAV1, and ELAVL1, which are critical to spermatogenesis. However, low folate levels did not increase the methylation levels of the promoter regions of ESR1, CAV1, and ELAVL1 in human sperm DNA. Thus, folate deficiency impairs spermatogenesis may partly due to inhibiting the expression of these genes. Thus future research should determine the significance of sufficient folate status in male fertilization and subsequent pregnancy outcomes.

Vitamin D Deficiency in Relation to the Risk of Metabolic Syndrome in Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus.

Vitamin D deficiency is highly prevalent all over the world and dietary intakes of vitamin D are very low in China. In this study we aimed to determine whether vitamin D deficiency is associated with increased risk of metabolic syndrome (MetS) among Chinese type 2 diabetes mellitus (T2DM) patients aged over 50 y. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured in a cross-sectional sample of 270 T2DM patients aged over 50 y from Zhejiang. Data on demographic characteristics, anthropometry and other variables were collected. The mean of serum 25(OH)D was 22.93 ng/mL, and percentages of vitamin D deficiency and insufficiency were 43.71% and 39.63%, respectively. Serum 25(OH)D concentrations were significantly lower in subjects with MetS than in those without MetS (21.74 vs 24.96 ng/mL, p=0.001), and the prevalence of MetS significantly increased according to tertiles of serum 25(OH)D concentrations. After adjusting for multivariate factors, the adverse effect of lower serum 25(OH)D concentrations was significant (OR: 3.26, 95% CI: 1.03-7.34; p=0.044) in the group with BMI≥24 kg/m2 while the change in OR of MetS for each 10 ng/mL decrease in the serum 25(OH)D concentrations was 2.03 (95% CI: 1.10-3.79). These results suggest that serum 25(OH)D deficiency may be a risk factor of MetS among Chinese type 2 diabetic patients, especially in the T2DM with BMI≥24 kg/m2. The challenge is determining the mechanisms of vitamin D action for recommendation of vitamin D supplementation that reduces the risks of MetS and progression to T2DM.