Polystyrene nanoplastics induce lipophagy via the AMPK/ULK1 pathway and block lipophagic flux leading to lipid accumulation in hepatocytes.

Micro- and nanoplastic pollution has emerged as a significant global concern due to their extensive presence in the environment and potential adverse effects on human health. Nanoplastics can enter the human circulatory system and accumulate in the liver, disrupting hepatic metabolism and causing hepatotoxicity. However, the precise mechanism remains uncertain. Lipophagy is an alternative mechanism of lipid metabolism involving autophagy. This study aims to explore how polystyrene nanoplastics (PSNPs) influence lipid metabolism in hepatocytes via lipophagy. Initially, it was found that PSNPs were internalized by human hepatocytes, resulting in decreased cell viability. PSNPs were found to induce the accumulation of lipid droplets (LDs), with autophagy inhibition exacerbating this accumulation. Then, PSNPs were proved to activate lipophagy by recruiting LDs into autophagosomes and block the lipophagic flux by impairing lysosomal function, inhibiting LD degradation. Ultimately, PSNPs were shown to activate lipophagy through the AMPK/ULK1 pathway, and knocking down AMPK exacerbated lipid accumulation in hepatocytes. Overall, these results indicated that PSNPs triggered lipophagy via the AMPK/ULK1 pathway and blocked lipophagic flux, leading to lipid accumulation in hepatocytes. Thus, this study identifies a novel mechanism underlying nanoplastic-induced lipid accumulation, providing a foundation for the toxicity study and risk assessments of nanoplastics.

Establishment of a Dual-Signal Enhanced Fluorescent Aptasensor for Highly Sensitive Detection of Ochratoxin A.

A robust and versatile dual-signal enhanced fluorescent aptasensor was developed for ochratoxin A (OTA) detection based on fluorescence resonance energy transfer between 5-carboxyfluorescein (FAM) and Super Green I (SG) fluorophores as the donor and graphene oxide (GO) nanosheet as the acceptor. Abundant SG probes were adsorbed into the FAM-complementary DNA (cDNA)-aptamer double-stranded structure to achieve remarkably enhanced fluorescence responses. Without OTA, the FAM-cDNA-SG conjugates coexisted with GO nanosheets, exhibiting strong fluorescence signals. In the presence of OTA, it was captured by the aptamers to release cDNA-FAM and SG probes, which were adsorbed by GO, leading to OTA-dependent fluorescence quenching. The changed fluorescence intensity was measured for accurate quantitation of OTA. Under optimum conditions, the dual-signal enhanced fluorescent aptasensor realized fascinating sensitivity with a limit of detection of 0.005 ng/mL and a wide concentration range of 0.02-20 ng/mL, as well as high selectivity for OTA over other interfering substances, excellent accuracy with average recoveries of 91.37-116.83% in the fortified malt matrices, and superior reliability and practicability in actual samples. This FAM-cDNA-aptamer-SG/GO nanosheet-based aptasensing platform could be extended to monitor other contaminants or trace molecules in food, environmental, and diagnostic fields by altering the corresponding aptamers.

18F-Labeled PET Tracers Specific for Adenosine A2A Receptor: Design, Synthesis, and Biological Evaluation.

By modifying the structures of targeted A2AR antagonists and tracers, novel compounds 3, 7a, 9, 12c, and BIBD-399 were designed and synthesized. In vitro inhibition experiments demonstrated that 3, 12c, and BIBD-399 have high affinity for A2AR. [18F]3 and [18F]BIBD-399 were successfully synthesized. In terms of biological distribution, the brain uptake of [18F]MNI-444 exhibits greater than that of [18F]3 and [18F]BIBD-399. PET imaging shows that [18F]3 is off-target in the brain, while [18F]BIBD-399 and [18F]MNI-444 can be specifically imaged in regions with high A2AR expression. Differently, [18F]BIBD-399 could quickly reach equilibrium in the targeted region within 10 min after administration, while [18F]MNI-444 shows a slowly increasing trend within 2 h of administration. [18F]BIBD-399 is mainly metabolized by the liver and kidney, and there is no obvious defluorination in vivo. Additional in vitro autoradiography showed that the striatal signals of [18F]BIBD-399 and [18F]MNI-444 were inhibited by the A2AR antagonist SCH442416 but not by the A1R antagonist DPCPX, demonstrating the high A2AR binding specificity of [18F]BIBD-399. Molecular docking further confirms the high affinity of MNI-444 and BIBD-399 for A2AR. Further tMCAo imaging showed that [18F]BIBD-399 can sensitively distinguish between infarcted and noninfarcted sides, a capability not observed with [18F]MNI-444. Given its pharmacokinetic properties and the ability to identify lesion regions, [18F]BIBD-399 has potential advantages in monitoring A2AR changes, meriting further clinical investigation.

A case-control study of urinary concentrations of bisphenol A, bisphenol F, and bisphenol S and the risk of papillary thyroid cancer.

The incidence of thyroid cancer (TC), especially papillary thyroid cancer (PTC), has dramatically increased globally. Whereas some endocrine disruptors have been linked to neoplastic processes, the associations between human exposure to bisphenol analogs and the risk of TC remain unclear. This present case-control study examined the associations between the urinary concentrations of bisphenol A (BPA) and other bisphenols, namely bisphenol F (BPF) and bisphenol S (BPS), and the risk of PTC. After adjusting for confounders and creatinine standardization, significantly positive associations were observed for BPF (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.27-2.54), but negative associations observed for BPA (OR = 0.38, 95% CI = 0.19-0.77) and BPS (OR = 0.63, 95% CI = 0.43-0.93), in the total population. However, after stratification by age and smoking, statistical significance was retained only in non-smoking women, suggesting the adverse effects of BPF exposure on PTC risk, especially in women. These findings require replication and confirmation in further research.

[Evolutionary characterization of HA1 of influenza H1N1 hemagglutinin gene surveyed in 1981-2005 in China].

To understand the evolutionary characterization of HA1 of H1N1 influenza virus HA gene circulaing from 1981 to 2005 in China, viral RNAs of 370 H1N1 strains were extracted and transcribed into cDNA by reverse transcriptase and amplified by PCR. The products of PCR were sequenced. The sequences were analyzed through biometic software. The results showed that all the four antigenic sites were mutated, bigger change occurred on the Sb and Ca sites; the 130 loop of receptor binding sites(RBS) of HA1 amino acid deleted at the 134th site in 1991 firstly, then the number of the deleted strains were increasing, since 2000, all the strains had deleted at the 134th site, and simultaneously, the amino acid at 137th site was substituted by S for T. The change of HA1 glycosylation sites was found and 7 sites kept stable from 2000 to 2005. The H1N1 strains of the same year almost clustered in the same group on the phylogenetic tree and were irrelevant to virus isolated time and area. There appeared two groups of 2005 H1N1 virus strains that differed in time of virus isolation.

[Development of methods for detection of H5N1 from human clinical specimens].

BACKGROUND: To establish a method for H5N1 RNA detection and laboratory diagnosis of suspected human avian influenza (H5N1) virus infected cases. METHODS: The typing and sub-typing primers were designed according to M and H5 and N1 gene respectively, and the RT-PCR and real-time PCR were developed using these primers. RESULTS: The RT-PCR and real-time PCR could be used for H5N1 detection specifically, and there was no cross reaction with other influenza subtypes such as H1 and H3. The sensitivity for RT-PCR and real-time PCR was 1 TCID50 and 0.01 TCID50 respectively. Thirteen laboratory confirmed human H5N1 cases were detected from 42 suspected cases by using these methods. CONCLUSION: The established RT-PCR and real-time PCR methods can be used for laboratory detection of suspected human H5N1 cases.

[Resistance to amantadine of epidemic strain of H3 subtype influenza virus: a primary study].

OBJECTIVE: To study the resistance to amantadine of epidemic strain of H3 subtype influenza virus. METHODS: Forty-one strains of influenza virus were isolated from pediatric patients with influenza in Beijing 2004-2005 and were identified as H3 subtype. RNA was extracted. Thirty of the 40 strains were resistant to amantadine with a resistance rate of 75%. The M2 gene ion channel fragments were amplified by one-step RT-PCR, sequenced, and then underwent systemic tree analysis. RESULTS: M2 ion channel associated gene fragment with a molecular size of 153 bp was obtained. The amino acid at the site 31 changed from serine into asparagines, a mutation identical to that of the reference strain A/PR8/34 resistant to amantadine. CONCLUSION: The resistance rate to amantadine is high among the epidemic strains of H3 subtype influenza virus in China. The associated mutation occurs at the site 31 of M2 protein.