The Impact of Visceral Adiposity on Testosterone Levels in American Adult Men: A Cross-Sectional Analysis.

BACKGROUND Testosterone decline and deficiency importantly affect men's health, and may be associated with excessive deposition of visceral adipose tissue. This study was conducted to explore the association between visceral adiposity index (VAI) and testosterone level. MATERIAL AND METHODS A total of 1551 participants from the NHANES 2013-2013 cycle and 2015-2016 cycle were selected for our analyses. The VAI index was calculated based on waist circumference (WC), body mass index (BMI), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-c), and serum testosterone was measured by isotope dilution liquid chromatography tandem mass spectrometry. Multivariable adjusted linear and logistic regression were utilized to investigate the associations between VAI index and testosterone level and testosterone deficiency, respectively. Additionally, subgroup analyses were performed to identify sensitive populations. RESULTS A total of 1551 participants with mean VAI index of 1.95±0.08 were eligible for our analysis. After adjusting for all potential cofounders, men with higher VAI index displayed a lower level of total testosterone level (ß: -11.74, 95% CI: -17.33, -6.15, P<0.0001), and higher risk of testosterone deficiency (OR: 1.24, 95% CI: 1.09, 1.40, P=0.0022). Comparing to VAI quartile 1, quartile 4 showed the most decreased testosterone level (ß: -94.59, 95% CI: -130.04, -59.14, P<0.0001), and highest risk of testosterone deficiency (OR: 5.07, 95% CI: 2.41,10.63, P<0.0001). Subgroup analysis demonstrated that VAI index was strongly related to testosterone level and testosterone deficiency in aged and obese men. CONCLUSIONS Men with higher VAI index displayed lower testosterone levels and higher risk of testosterone deficiency, especially in aged men and obese men.

Gold Nanoparticles Reduce Food Sensation in Caenorhabditis elegans via the Voltage-Gated Channel EGL-19.

Introduction: The increasing use of gold nanoparticles (Au NPs) in the medical field has raised concerns about the potential adverse effect of Au NPs exposure. However, it is difficult to assess the health risks of Au NPs exposure at the individual organ level using current measurement techniques. Methods: The physical and chemical properties of Au NPs were characterized by transmission electron microscope (TEM), Fourier transform infrared (FTIR), and zeta sizer. The RNA-seq data of Au NPs-exposed worms were analyzed. The food intake was measured by liquid culture and Pharyngeal pumping rate. The function of the smell and taste neurons was evaluated by the chemotaxis and avoidance assay. The activation of ASE neurons was analyzed by calcium imaging. The gene expression of ins-22 and egl-19 was obtained from the C. elegans single cell RNA-seq databases. Results: Our data analysis indicated that 62.8% of the significantly altered genes were functional in the nervous system. Notably, developmental stage analysis demonstrated that exposure to Au NPs interfered with animal development by regulating foraging behavior. Also, our chemotaxis results showed that exposure to Au NPs reduced the sensation of C. elegans to NaCl, which was consistent with the decrease in calcium transit of ASEL. Further studies confirmed that the reduced calcium transit was dependent on voltage-gated calcium channel EGL-19. The neuropeptide INS-22 was partially involved in Au NPs-induced NaCl sensation defect. Therefore, we proposed that Au NPs reduced the calcium transit in the ASEL neuron through egl-19-dependent calcium channels. It was partially regulated by the DAF-16 targeting neuropeptide INS-22. Discussion: Our results demonstrate that Au NPs affect food sensation by reducing the calcium transit in ASEL neurons, which further leads to reduced pharynx pumping and feeding defects. The toxicology studies of Au NPs from worms have great potential to guide the usage of Au NPs in the medical field such as targeted drug delivery.

Multiple generation exposure to ZnO nanoparticles induces loss of genomic integrity in Caenorhabditis elegans.

Zinc oxide nanoparticles (ZnO NPs) are commonly used in industrial and household applications, prompting the assessment of their associated health risks. Previous studies indicated that ZnO NPs can induce somatic cell mutations, while the aging process appears to increase the mutagenicity of ZnO NPs. However, little is known about the influence of ZnO NPs on genome stability of germ cells, and non-exposed progeny. Here we show that 20 nm ZnO NPs exposure disrupts germ cell development, and elevates the overall mutation frequency of germ cells in Caenorhabditis elegans (C. elegans). We observed that pristine ZnO NPs elicit germ cell apoptosis to a greater extent than the 60-day aged ZnO NPs. By treating parental worms with ZnO NPs for seven successive generations, whole-genome sequencing data revealed that, although the frequency of point mutations is kept unchanged, large deletions are significantly increased in F8 worms. Furthermore, we found that the mutagenicity of ZnO NPs might be partially attributed to the release of Zn2+ ions. Together, our results demonstrate the genotoxic effects of ZnO NPs on germ cells, and the possible underlying mechanism. These findings suggest that germ cell mutagenicity is worthy of consideration for the health risk assessment of engineered NPs.

Cage-modified hypocrellin against multidrug-resistant Candida spp. with unprecedented activity in light-triggered combinational photodynamic therapy.

Infections caused by multidrug-resistant fungi pose a devastating threat to human health worldwide, making new antifungal strategies urgently desired. Antimicrobial photodynamic therapy (aPDT) has gained increasing attention due to its potential in fighting against fungal infection. However, the preparation of highly efficient and water-soluble photosensitizers (PSs) for this purpose remains a challenge. Herein, we present a new strategy to prepare powerful PSs for efficient aPDT by introducing a porous cage compound, which could facilitate the transportation of O2 and reactive oxygen species (ROS). Specifically, the natural PS hypocrellin A (HA) was attached to a novel organic cage compound (covalent organic polyhedra 1 tied, COP1T) with polyethylene glycol (PEG) chains to improve its water solubility. It was found that the resulting COP1T-HA exhibited in vitro antifungal efficiency several folds higher compared to the free HA in fighting against four types of multidrug-resistant fungal planktonic cells and biofilms, including the "super fungus" Candida auris. Interestingly, the red-shift of COP1T-HA adsorption led to the realization of phototheranostic aPDT for cage-modified HA or derivatives. Additionally, COP1T-HA exhibited good biocompatibility, excellent disinfection capacity and wound healing efficiency without obvious toxic effects in vivo of rat model. With further development and optimization, COP1T-HA has great potential to become a new class of antifungal agent to fight against drug-resistant pathogens.

GLI1 amplified/fused mesenchymal tumor: A case report and review of the literature.

Glioma-associated oncogene homologue 1 (GLI1) is an important transcription factor downstream of Hedgehog (HH) signaling pathway, and can be used as a marker of HH signaling pathway activation. GLI1 gene translocations have been reported in several tumor types, including those associated with t(7;12) translocated dermatocytoma, plexus fibromyxoma, and gastroblastoma and other types of malignant soft tissue tumors, whereas GLI1 amplification is actually very rare in tumors. In this case report, we describe for the first time a tumor in the right mandibular gingiva, which is consistent with GLI1 amplified/fused mesenchymal tumor. The tumor cells are elliptic, polygonal and spindle tumor cells growing into nests and segments, lobulated and occasionally mitotic. The identification of these pathological features can help guide pathologists to make appropriate diagnosis and, if necessary, follow-up molecular tests. Our case has been treated with surgical resection. To date, no recurrence or metastasis has occurred and the prognosis is good.

The Role of Apoptosis Pathway in the Cytotoxicity Induced by Fresh and Aged Zinc Oxide Nanoparticles.

Zinc oxide nanoparticles (ZnO NPs) are used in a wide range of applications including industry, commercial products and medicine field. Numerous mechanistic studies for ZnO NPs' toxicity were performed on pristine (fresh) NPs. However, the cytotoxicity induced by the transformed (aged) ZnO NPs and the underlying mechanisms remain unclear. Here, we observed the physicochemical transformation of ZnO NPs underwent over time, followed by evaluating the cytotoxicity of fresh and aged NPs. We found that fresh ZnO NPs induced higher apoptosis level than their aged counterparts. Accordingly, RNA sequencing data from aged ZnO NP-treated human-hamster hybrid (AL) cells showed that p53, PI3k-Akt, FoXO, Glutathione, ErbB, HIF-1, Oxytocin and Jak-STAT signaling pathways were enriched but no apoptosis pathway. Quantitative PCR results revealed the significantly higher mRNA level of IL1B and CD69 in fresh NP-treated groups compared to that of aged ZnO NP- and zinc chloride-treated groups. The above results indicated that the lower cytotoxicity of aged ZnO NPs is partially attributed to their reduced potency in inducing apoptosis. The transcriptional regulation of multiple signal pathways activated by aged NPs may help to build the cellular homeostasis. Taken together, our findings highlight the influence of aging (environmental transformation) process of ZnO NPs on their toxicities and biological consequences.