X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl)phthalate-induced testis toxicity

As a widely used plasticizer,di-(2-ethylhexyl)phthalate(DEHP)is known to induce significant testicular injury.However,the potential mechanism and effects of pubertal exposure to DEHP on testis development remain unclear.In vivo,postnatal day(PND)21 male rats were gavaged with 0,250,and 500 mg/kg DEHP for ten days.Damage to the seminiferous epithelium and disturbed spermatogenesis were observed after DEHP exposure.Meanwhile,oxidative stress-induced injury and pyroptosis were activated.Both endoplasmic reticulum(ER)stress and mitophagy were involved in this process.Monoethylhexyl phthalate(MEHP)was used as the biometabolite of DEHP in vitro.The GC-1 and GC-2 cell lines were exposed to 0,100μM,200μM,and 400μM MEHP for 24 h.Reactive oxygen species(ROS)generation,oxidative stress damage,ER stress,mitophagy,and pyroptosis were significantly increased after MEHP exposure.The ultrastructure of the ER and mitochondria was destroyed.X-box binding protein 1(XBP1)was observed to be activated and translocated into the nucleus.ROS generation was inhibited by acetylcysteine.The levels of antioxidative stress,ER stress,mitophagy,and pyroptosis were decreased as well.After the administration of the ER stress inhibitor 4-phenyl-butyric acid,both mitophagy and pyroptosis were inhibited.Toyocamycin-induced XBP1 down-regulation decreased the levels of mitophagy and pyroptosis.The equilibrium between pyroptosis and mitophagy was disturbed by XBP1 accumulation.In summary,our findings confirmed that DEHP induced a ROS-mediated imbalance in pyroptosis and mitophagy in immature rat testes via XBP1.Moreover,XBP1 might be the key target in DEHP-related testis dysfunction.

Promotion of liquid-to-solid phase transition of cGAS by Baicalein suppresses lung tumorigenesis

Dear Editor,Kras and p53 mutation are among the most common gene mutations in lung cancer,which has both the highest incidence and mortality rate among cancers.1 Kras/p53 mutation also causes mitochondrial dysfunction,which has been implicated to promote the inflammation-to-cancer transition.2 We established a lung adenocarcinoma model by using conditional alleles of KrasLSLG12D/p53flox/flox in mice3 to evaluate the effect of Baicalein(5,6,7-trihydroxyflavone),a principal component of Scutellaria baicalensis in traditional Chinese medicine,4 on the initiation and progression of lung cancer.Cre-mediated expression of KrasG12D and deletion of p53 caused obvious tumor lesions in the lung,which were strongly inhibited by the administration of Baicalein(Fig.1a,b and Supplementary Fig.1a,b),indicating that Baicalein is highly potent in inhibiting the progression of primary lung cancer.

Noninvasive Low-Frequency Pulsed Focused Ultrasound Therapy for Rheumatoid Arthritis in Mice

Rheumatoid arthritis(RA)is a common autoimmune disease characterized by chronic and progressive inflammation of the synovium.Focused ultrasound therapy is an increasingly attractive alternative for treating RA owing to its noninvasiveness;however,it remains unclear which immune subsets respond to ultrasound stimulation.In this study,we showed that spleen-targeted low-frequency pulsed focused ultrasound(LFPFU)effectively improved the severity of arthritis in an arthritis mouse model established in DBA/1J mice.Additionally,we performed in-depth immune profiling of spleen samples from RA mice,RA mice that underwent ultrasound therapy,and healthy controls using mass cytometry along with extensive antibody panels and identified the immune composition of 14 cell populations,including CD4^(+)/CD8^(+)T cells,B cells,natural killer cells,and dendritic cells.Moreover,multidimensional analysis according to cell-surface markers and phenotypes helped in identifying 4 and 5 cell subpopulations among T and myeloid cells,respectively,with 6 T cell subsets and 3 myeloid cell subsets responsive to ultrasound therapy among the 3 groups.Of these cell subsets,CD8^(+)T cell subsets showed a unique response to ultrasound stimulation in RA mice.Specifically,CD8^(+)T cells show a noticeable correlation with the degree of arthritis progression and could serve as an indicator for spleen-focused ultrasound-based therapy.Furthermore,single-cell RNA sequencing of spleen cells revealed the importance of T,B,and myeloid cell populations in the anti-inflammatory pathway.These results elucidated the unique cell subsets and transcriptome of splenic cells responsive to LFPFU and demonstrated the potential of spleen-focused ultrasound stimulation in the treatment of inflammatory diseases.

Highly concentrated phenanthrenequinone-doped poly(MMA-co-ACMO) for volume holography

Novel composite materials are synthesized by incorporating N-acryloylmorpholine(ACMO) in highly concentrated phenanthrenequinone(PQ) doped poly(methyl methacrylate)(PMMA). The photosensitizer concentration of PQ was increased from 0.7 wt. % to 1.8 wt. %. The doping of ACMO component results in a higher diffraction efficiency and photosensitivity than a typical PQ/PMMA system. The enhanced performance of the material may stem from the ACMO molecules, which might open a new route for improving the holographic performance of the PQ/PMMA photopolymer.