Polystyrene nanoplastics induce cardiotoxicity by upregulating HIPK2 and activating the P53 and TGF-ß1/Smad3 pathways.

Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-ß1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions.

Persistent production of multiple active species with copper doped zinc gallate nanoparticles for light-independent photocatalytic degradation of organic pollutants.

Photocatalysis is considered as an environmentally friendly and sustainable method as it can produce active species to degrade pollutants. However, its applications are hindered by the turbidity of pollutants and the requirements for continuous or repeated in situ irradiation. To avoid the need for continuous in situ irradiation in the photocatalytic process, herein we report the doping of Cu(II) ions into zinc gallate (ZnGa2O4) as traps to capture photo-generated electrons. In this way, long lifetime charge release and separation were effectively achieved for the persistent degradation of organic dyes in wastewater. The Cu(II) doped ZnGa2O4 (ZGC) nanoparticles with a small size about 7.7 nm synthesized via a hydrothermal method exhibited a persistent photocatalytic activity with continuous production of reactive oxygen species for at least 96 h without in situ irradiation due to its unique electronic structure and carrier transport path, and enabled to degrade 82.2 % of rhodamine B in 1 h. Further investigation revealed that the doped Cu(II) ions occupied the octahedral sites of ZGC and highly increased the persistent production and availability of active species for the persistent degradation of organic dyes under pre-illuminated conditions.

Self-evolving persistent luminescence nanoprobes for autofluorescence-free ratiometric imaging and on-demand enhanced chemodynamic therapy of pulmonary metastatic tumors.

Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situ excitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+ and Mn2+ released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.

The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

Afterglow Performance of Phenylenevinylene-Based Semiconducting Polymer Nanoparticles Doped with Photosensitizers Containing Electron-Withdrawing Groups.

It is usually believed that doping with photosensitizers capable of generating singlet oxygen (1O2) plays a pivotal role in enhancing the afterglow performance of semiconducting polymer nanoparticles (SPNs). However, the effect of doping photosensitizer bearing electron-withdrawing groups has not been reported. Here we report the effect of doping with six photosensitizers possessing different electron-withdrawing groups on the afterglow performance of SPNs using poly[(9,9-di(2-ethylhexyl)-9H-fluo-rene-2,7-vinylene)-co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)] (PF-MEHPPV) as substrate. It was found that the afterglow performance of SPNs was significantly influenced by doping with photosensitizers bearing electron-withdrawing groups. For the doped photosensitizers with strong electron-withdrawing groups, the stronger the electron-withdrawing ability of the group, the worse of the afterglow performance of the SPN regardless of the 1O2 generation ability of the photosensitizer. When the doped photosensitizer exhibited weak or none electron-withdrawing effect, the 1O2 generation ability of the photosensitizer played a dominant role on the afterglow performance of the SPNs. This work deepens the understanding of the design and synthesis of SPNs with different afterglow properties.

Size-independent boosting of near-infrared persistent luminescence in nano-phosphors via a magnesium doping strategy.

Near-infrared (NIR)-emitting persistent luminescence nanoparticles (PLNPs) are ideal optical imaging contrast reagents characterized by autofluorescence-free optical imaging for their frontier applications in long-term bioimaging. Preparation of uniform small-sized PLNPs with excellent luminescence performance is crucial for biomedical applications, but challenging. Here, we report a facile magnesium doping strategy to achieve size-independent boost of NIR persistent luminescence in typical and most concerned ZnGa2O4:Cr3+ PLNPs. This strategy relies on the doping of Mg2+ ions that with similar size of Zn2+ ions in the host lattice matrix, and concomitant to the electron traps tailoring tuned by varying the feed ratio of Mg2+. The optimum Mg2+-doped PLNPs give a long afterglow time (signal-to-noise ratio (SNR) = 31.6 at 30 d) without changing the desirable uniform sub-10 nm size of the original nanocrystals. The appropriate increase of the depth and concentration of electron trap contribute jointly to the enhancement of lifetime (488 % longer, 20.57 s) and afterglow time for 700 nm persistent luminescence. Meanwhile, these PLNPs keep the original excellent rechargeability and promote over 60 times increase of SNR in renewable in vivo imaging. This simple strategy provides a basis for new opportunities to address the critical challenge of effective optical performance boost in small-sized PLNPs.

Inulin alleviates perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure-induced intestinal toxicity by reshaping the gut microbiota and suppressing the enteric-origin LPS/TLR4/NF-κb pathway in dams and pups.

Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure.

Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study.

BACKGROUND: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear. METHODS: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia. RESULTS: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors. CONCLUSIONS: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.