Hydrogen sulfide ameliorates isoflurane-induced cognitive impairment in mice: Implication of caspase-3 activation

Purpose: Isoflurane could induce cognitive impairment and activate caspase-3. However, the mechanism of action is unclear and target  interventions are unavailable. The present study examined the potential protective function of hydrogen sulfide (H2S) against isoflurane-induced cognitive impairment.Methods: Effects of NaHS (5 mg/kg) on cognitive impairment induced by isoflurane (1.4% for 2 h) were assessed using a fear-conditioning test in a group of 8-month old mice. H4 human neuroglioma cells, which were transfected with upregulated human amyloid precursor protein were treated for 3 or 6 h with 2% isoflurane, in the presence of 100-μM NaHS in the mice. A group of mice treated with normal saline in place of the NaHS in each case served as control. Western blotting, fluorescence assay, and a mitochondrial swelling assay were employed to observe the results of caspase-3 activation, mitochondrial dysfunction, and ROS and ATP levels.Results: NaHS significantly mitigated isoflurane-induced cognitive impairment in mice. In cultured cells, NaHS reduced caspase-3 activation, ROS, mitochondria membrane reduction, mitochondrial permeability transition pore opening, and cellular ATP level. NaHS could ameliorate cognitiveimpariment induced by isoflurane through inhibiting caspase-3 activation, oxidative stress, and mitochondrial dysfunction.Conclusion: These results indicate that hydrogen sulfide (H2S) has potential protective function against isoflurane-induced cognitive impairment. Further investigation of NaHS as an intervention to attenuate anesthesia-associated neurotoxicity is vital. Keywords: Hydrogen sulfide, isoflurane-cognition，fear conditioning，neurotoxicit

LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling

While the antiandrogen enzalutamide (Enz) extends the castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months, it might also result in some adverse effects via inducing the neuroendocrine differentiation (NED). Here we found that lncRNA-p21 is highly expressed in the NEPC patients derived xenograft tissues (NEPC-PDX). Results from cell lines and human clinical sample surveys also revealed that lncRNA-p21 expression is up-regulated in NEPC and Enz treatment could increase the lncRNA-p21 to induce the NED. Mechanism dissection revealed that Enz could promote the lncRNA-p21 transcription via altering the androgen receptor (AR) binding to different androgen-response-elements, which switch the EZH2 function from histone-methyltransferase to non-histone methyltransferase, consequently methylating the STAT3 to promote the NED. Preclinical studies using the PDX mouse model proved that EZH2 inhibitor could block the Enz-induced NED. Together, these results suggest targeting the Enz/AR/lncRNA-p21/EZH2/STAT3 signaling may help urologists to develop a treatment for better suppression of the human CRPC progression

Novel targeting of PEGylated liposomes for codelivery of TGF-β1 siRNA and four antitubercular drugs to human macrophages for the treatment of mycobacterial infection: a quantitative proteomic study

Tuberculosis (TB) is still a major public health issue in developing countries, and its chemotherapy is compromised by poor drug compliance and severe side effects. This study aimed to synthesize and characterize new multimodal PEGylated liposomes encapsulated with clinically commonly used anti-TB drugs with linkage to small interfering RNA (siRNA) against transforming growth factor-β1 (TGF-β1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages that were the host cells of mycobacterium infection. The biological effects of the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis, autophagy, and the gene silencing efficiency of TGF-β1 siRNA in human macrophages. We also explored the proteomic responses to the newly synthesized NP-siRNA liposomes using the stable isotope labeling with amino acids in cell culture approach. The results showed that the multifunctional PEGylated liposomes were successfully synthesized and chemically characterized with a mean size of 265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and TGF-β1 siRNA were endocytosed efficiently by human macrophages as visualized by transmission electron microscopy and scanning electron microscopy. Furthermore, the liposomes showed a low cytotoxicity toward human macrophages. There was no significant effect on cell cycle distribution and apoptosis in THP-1-derived macrophages after drug exposure at concentrations ranging from 2.5 to 62.5 μg/mL. Notably, there was a 6.4-fold increase in the autophagy of human macrophages when treated with the NP-siRNA liposomes at 62.5 μg/mL. In addition, the TGF-β1 and nuclear factor-κB expression levels were downregulated by the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway Analysis data showed that there were over 40 signaling pathways involved in the proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160 proteins mapped. The top five canonical signaling pathways were eukaryotic initiation factor 2 signaling, actin cytoskeleton signaling, remodeling of epithelial adherens junctions, epithelial adherens junction signaling, and Rho GDP-dissociation inhibitor signaling pathways. Collectively, the novel synthetic targeting liposomes represent a promising delivery system for anti-TB drugs to human macrophages with good selectivity and minimal cytotoxicity

Thyroid dose assessments due to inhalation of 131I for nuclear medicine workers

BackgroundIn general, medical staff who work in nuclear medicine should be entirely safe in their professional environment. Nevertheless, we already know that the working environment of the nuclear medicine staff is not completely safe due to the handling of high amounts of radionuclides for diagnostic and therapy applications, which is especially relevant for 131I (as a non-sealed source).PurposeThe goal of this study was to assess the inhaled 131I thyroid dose in nuclear medicine workers and to introduce a simple method for internal exposure monitoring.MethodsUsing 2-IN*2-in NaI (Tl) scintillation spectrometer and its supporting software (InSpector Maintenance Utility and Genie 2000), from 2019 to 2021, internal thyroid irradiation monitoring, an internal thyroid irradiation monitoring investi A NaI (Tl) scintillation spectrometer and its sugation was carried out for 3 consecutive years, between 2019 and 2021, in staff members of nuclear medicine departments engaged with iodine therapy.Results131I activity was found highest in the thyroid of nuclear medicine workers involved with the manual packaging and delivery of the radioisotope, while it was not detected in staff members involved with the automatic packaging and drug delivery. The activity range was found to be 30.00 ± 6.60–6070.00 ± 1335.40 Bq for the exposed personnel, and the estimated dose was 0.05–6.77 mSv. In 2021, three workers had an annual equivalent dose above 5 mSv.ConclusionBy monitoring the thyroid 131I in staff members of the nuclear medicine department, it was found that there are 131I internal occupational exposure risks. The best solution is automatic packaging and drug delivery

Can the sex ratio of the spiralling whitefly (Aleurodicus dispersus) be described by local mate competition?

ABSTRACT Background: Local mate competition theory predicts a female-biased sex ratio if one or a few hymenopteran foundresses, such as parasitoid wasps, oviposit in a local patch, and a less female-biased sex ratio as the number of foundresses increases. Although hemipterans, whiteflies are also haplodiploid insects, and the spatial structure of whitefly populations is similar to that of wasps. Question: Do whitefly sex ratios match the theoretical predictions of local mate competition? Organism: The spiralling whitefly, Aleurodicus dispersus Russell (Hemiptera: Aleyrodidae), a newly invasive, destructive pest on Hainan Island, China. Methods: We investigated the effects of the number of foundresses on the sex ratio of A. dispersus. Results: Offspring sex ratio was female-biased when only one foundress oviposited in a patch. Sex ratio increased with the number of foundresses. When only one foundress laid eggs in a patch, offspring sex ratio declined as the number of offspring increased. Male offspring emerged earlier than female offspring. Conclusion: Local mate competition predicted the trends in sex ratio of the spiralling whitefly

Humidity resistant fabrication of CH3NH3PbI3 perovskite solar cells and modules

A humidity resistant and versatile fabrication method for the production of very high quality, organic-inorganic perovskite films, solar cells and solar modules is presented. By using ethyl acetate as an anti-solvent during deposition, perovskite solar cells with power conversion efficiencies (PCEs) up to 15% were fabricated in a 75% relative humidity (RH) environment. Ethyl acetate acts as a moisture absorber during spin-coating, protecting sensitive perovskite intermediate phases from airborne water during film formation and annealing. We have demonstrated the manufacture of 50 mm x 50 mm series interconnected modules with PCEs in excess of 10% for 13.5 cm2 devices processed in air at 75%RH and 11.8% at 50%RH. To the best of our knowledge, these results represent the highest efficiency for perovskite solar modules processed under high humidity ambient conditions. This new deposition protocol allows for low-cost, efficient and consistent device fabrication in humid climates and uncontrolled laboratories

Evaluating biochar and its modifications for the removal of ammonium, nitrate, and phosphate in water

Removal of nitrogen (N) and phosphorus (P) from water through the use of various sorbents is often considered an economically viable way for supplementing conventional methods. Biochar has been widely studied for its potential adsorption capabilities for soluble N and P, but the performance of different types of biochars can vary widely. In this review, we summarized the adsorption capacities of biochars in removing N (NH4-N and NO3-N) and P (PO4-P) based on the reported data, and discussed the possible mechanisms and influencing factors. In general, the NH4-N adsorption capacity of unmodified biochars is relatively low, at levels of less than 20 mg/g. This adsorption is mainly via ion exchange and/or interactions with oxygen-containing functional groups on biochar surfaces. The affinity is even lower for NO3-N, because of electrostatic repulsion by negatively charged biochar surfaces. Precipitation of PO4-P by metals/metal oxides in biochar is the primary mechanism for PO4-P removal. Biochars modified by metals have a significantly higher capacity to remove NH4-N, NO3-N, and PO4-P than unmodified biochar, due to the change in surface charge and the increase in metal oxides on the biochar surface. Ambient conditions in the aqueous phase, including temperature, pH, and co-existing ions, can significantly alter the adsorption of N and P by biochars, indicating the importance of optimal processing parameters for N and P removal. However, the release of endogenous N and P from biochar to water can impede its performance, and the presence of competing ions in water poses practical challenges for the use of biochar for nutrient removal. This review demonstrates that progress is needed to improve the performance of biochars and overcome challenges before the widespread field application of biochar for N and P removal is realized

Hydrogen evolution enhancement of ultra-low loading, size-selected molybdenum sulfide nanoclusters by sulfur enrichment

Size-selected molybdenum sulfide (MoSx) nanoclusters obtained by magnetron sputtering and gas condensation on glassy carbon substrates are typically sulfur-deficient (x = 1.6 ± 0.1), which limits their crystallinity and electrocatalytic properties. Here we demonstrate that a sulfur-enriching method, comprising sulfur evaporation and cluster annealing under vacuum conditions, significantly enhances their activity towards the hydrogen evolution reaction (HER). The S-richness (x = 4.9 ± 0.1) and extended crystalline order obtained in the sulfur-treated MoSx nanoclusters lead to consistent 200 mV shifts to lower HER onset potentials, along with two-fold and more-than 30-fold increases in turnover frequency and exchange current density values respectively. The high mass activities (~111 mA mg-1 @ 400 mV) obtained at ultra-low loadings (~100 ng cm-2, 5 % surface coverage) are comparable to the best reported MoS2 catalysts in the literature