METTL3 catalyzes the formation of N6 -methyl-adenosine (m 6 A) which has important roles in regulating various biological processes. However, the in vivo function of Mettl3 remains largely unknown in mammals. Here we generated germ cell-specific Mettl3 knockout mice and demonstrated that Mettl3 was essential for male fertility and spermatogenesis. The ablation of Mettl3 in germ cells severely inhibited spermatogonial differentiation and blocked the initiation of meiosis. Transcriptome and m 6 A profiling analysis revealed that genes functioning in spermatogenesis had altered profiles of expression and alternative splicing. Our findings provide novel insights into the function and regulatory mechanisms of Mettl3-mediated m 6 A modification in spermatogenesis and reproduction in mammals.

N6-methyladenosine (m6A) RNA methylation is the most abundant modification on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. However, the in vivo functions of METTL3 and m6A modification in mammalian development remain unclear. Here, we show that specific inactivation of Mettl3 in mouse nervous system causes severe developmental defects in the brain. Mettl3 conditional knockout (cKO) mice manifest cerebellar hypoplasia caused by drastically enhanced apoptosis of newborn cerebellar granule cells (CGCs) in the external granular layer (EGL). METTL3 depletion–induced loss of m6A modification causes extended RNA half-lives and aberrant splicing events, consequently leading to dysregulation of transcriptome-wide gene expression and premature CGC death. Our findings reveal a critical role of METTL3-mediated m6A in regulating the development of mammalian cerebellum.

Poly(ADP-ribosyl)ation (PARylation) is an essential post-translational modification catalyzed by poly(ADP-ribose) polymerase (PARP) enzymes. Poly(ADP-ribose) polymerase 1 (PARP1) is a well-characterized member of the PARP family. PARP1 plays a crucial role in multiple biological processes and PARP1 activation contributes to the development of various inflammatory and malignant disorders, including lung inflammatory disorders, cardiovascular disease, ovarian cancer, breast cancer, and diabetes. In this review, we will focus on the role and molecular mechanisms of PARPs enzymes in inflammation- and metabolic-related diseases. Specifically, we discuss the molecular mechanisms and signaling pathways that PARP1 is associated with in the regulation of pathogenesis. Recently, increasing evidence suggests that PARP inhibition is a promising strategy for intervention of some diseases. Thus, our in-depth understanding of the mechanism of how PARPs are activated and how their signaling downstream effecters can provide more potential therapeutic targets for the treatment of the related diseases in the future is crucial.

Silanized aluminum borate whiskers (ABWs) of 4 wt%, silanized zirconium dioxide nanoparticles (nano-ZrO2) of 2 wt% were mixed with polymethyl methacrylate (PMMA) powder to get ZrO2-ABWs/PMMA composites. Titanium dioxide (TiO2), silver-supported titanium dioxide (Ag/TiO2), silver-supported zirconium phosphate (Novaron) and tetrapod-like zinc oxide whiskers (T-ZnOw) antibacterial agents of 3 wt% were mixed with ZrO2-ABWs/PMMA composites respectively to fabricate standard specimens. Plaque biofilms on the specimens surface were investigated for colony-forming units (CFUs). In addition, cytotoxicity and mechanical behavior were evaluated. Results showed that the CFUs values of S. mutans and C. albican biofilms on the four antibacterial composites surface were all reduced (p<0.05) compared to the blank and control groups. The antibacterial composites did not have an adverse effect on fibroblast growth in this study (p>0.05) except TiO2 and Ag/TiO2 groups of undiluted extracts. The flexural strength and surface hardness of Novaron and T-ZnOw groups were increased (p<0.05) compared to the control group.

Histone deacetylase 10 (HDAC10) is a member of the class II HDACs, and its role in cancer is emerging. In this study, we found that HDAC10 is highly expressed in lung cancer tissues. It resides mainly in the cytoplasm of lung cancer cells but resides in the nucleus of adjacent normal cells. Further examinations revealed that HDAC10 resides in the cytoplasm in multiple lung cancer cell lines, including the A549, H358 and H460 cell lines, but mainly resides in the nucleus of normal lung epithelial 16HBE cells. A leucine-rich motif, R505L506L507C508V509A510L511, was identified as its nuclear localization signal (NLS), and a mutant (Mut-505-511) featuring mutations to A at each of its original R and L positions was found to be nuclear-localization defective. Functional analysis revealed that HDAC10 promoted lung cancer cell growth and that its knockdown induced cell cycle arrest and apoptosis. Mechanistic studies showed that HDAC10 knockdown significantly decreased the phosphorylation of AKT at Ser473 and that AKT expression significantly rescued the cell cycle arrest and apoptosis elicited by HDAC10 knockdown. A co-immunoprecipitation assay suggested that HDAC10 interacts with AKT and that inhibition of HDAC10 activity decreases its interaction with and phosphorylation of AKT. Finally, we confirmed that HDAC10 promoted lung cancer proliferation in a mouse model. Our study demonstrated that HDAC10 localizes and functions in the cytoplasm of lung cancer cells, thereby underscoring its potential role in the diagnosis and treatment of lung cancer.

As past studies of self-control and Internet addiction showed mixed results, this meta-analysis of 83 primary studies with 80,681 participants determined whether (a) these students with less self-control had greater Internet addiction, and (b) age, culture, gender, Internet addiction measures, or year moderated these relations. We used a random-effects meta-analysis of Pearson product-moment coefficients r with Fisher’s z-transformation and tested for moderation with the homogeneity tests. The results showed a positive link between impulsivity and Internet addiction (r = 0.371, 95% CI = [0.311, 0.427]) and a negative link between restraint and Internet addiction (r = −0.362, 95% CI = [−0.414, −0.307]). The moderation analysis indicated that the correlation between impulsivity indicators and greater Internet addiction was stronger among undergraduates (18–22 years old) than among adolescents (10–17 years old). Furthermore, the negative link between a restraint indicator and Internet addiction was greater (a) among students in East Asia than those in Western Europe/North America, (b) among males than females and (c) when using the Internet addiction measures GPIUS or IAT rather than CIAS. Hence, these results indicate a negative link between self-control and Internet addiction, and this link is moderated by age, culture, gender, and Internet addiction measure.

The oxidative state of sunflower oil during high-temperature storage has been facing large challenges. In the study, the antioxidant effect of the essential oil of Angelica dahurica cv. Yubaizhi (ADEO) in sunflower oil was explored. In the high-temperature storage for 24 days at 65 °C, ADEO (800 ppm) was able to markedly inhibit the development of the acid value (AV), peroxide value (PV), p-anisidine value (AnV), total oxidation value (TOTOX), thiobarbituric acid reactive substances (TBARS), total polar compounds (TPC), and the absorbance at 232 and 268 nm (p < 0.01 or p < 0.05) of sunflower oil and to prominently inhibit the transformation between unsaturated fatty acids (UFA) and saturated fatty acids (SFA). Interestingly, the synergistic effect of ADEO (400 ppm) and tert-butyl hydroquinone (TBHQ, 100 ppm) was demonstrated. Furthermore, the sensory attributes such as flavor, taste, and overall acceptability of oxidized sunflower oil added by ADEO at 200, 400, and 800 ppm were memorably elevated (p < 0.05). Besides, one of its main compounds, myrcene, was demonstrated to be its active compound during the whole investigation. Consequently, TBHQ at 200 ppm could be substituted by ADEO at 800 ppm and myrcene at 69.8 ppm in the high-temperature storage at 65 °C of sunflower oil.

8‐Oxoguanine DNA glycosylase1 (OGG1)‐initiated base excision repair (BER) is the primary pathway to remove the pre‐mutagenic 8‐oxo‐7,8‐dihydroguanine (8‐oxoG) from DNA. Recent studies documented 8‐oxoG serves as an epigenetic‐like mark and OGG1 modulates gene expression in oxidatively stressed cells. For this new role of OGG1, two distinct mechanisms have been proposed: one is coupled to base excision, while the other only requires substrate binding of OGG1––both resulting in conformational adjustment in the adjacent DNA sequences providing access for transcription factors to their cis‐elements. The present study aimed to examine if BER activity of OGG1 is required for pro‐inflammatory gene expression. To this end, Ogg1/OGG1 knockout/depleted cells were transfected with constructs expressing wild‐type (wt) and repair‐deficient mutants of OGG1. OGG1's promoter enrichment, oxidative state, and gene expression were examined. Results showed that TNFα exposure increased levels of oxidatively modified cysteine(s) of wt OGG1 without impairing its association with promoter and facilitated gene expression. The excision deficient K249Q mutant was even a more potent activator of gene expression; whereas, mutant OGG1 with impaired substrate recognition/binding was not. These data suggested the interaction of OGG1 with its substrate at regulatory regions followed by conformational adjustment in the adjacent DNA is the primary mode to modulate inflammatory gene expression.