piRNA loading triggers MIWI translocation from the intermitochondrial cement to chromatoid body during mouse spermatogenesis.

The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory mechanism underpinning MIWI translocation, however, has remained elusive. We unveil that piRNA loading is the trigger for MIWI translocation from the IMC to CB. Mechanistically, piRNA loading facilitates MIWI release from the IMC by weakening its ties with the mitochondria-anchored TDRKH. This, in turn, enables arginine methylation of MIWI, augmenting its binding affinity for TDRD6 and ensuring its integration within the CB. Notably, loss of piRNA-loading ability causes MIWI entrapment in the IMC and its destabilization in male germ cells, leading to defective spermatogenesis and male infertility in mice. Collectively, our findings establish the critical role of piRNA loading in MIWI translocation during spermatogenesis, offering new insights into piRNA biology in mammals.

Engineered hsa-miR-455-3p-Abundant Extracellular Vesicles Derived from 3D-Cultured Adipose Mesenchymal Stem Cells for Tissue-Engineering Hyaline Cartilage Regeneration.

Efforts are made to enhance the inherent potential of extracellular vesicles (EVs) by utilizing 3D culture platforms and engineered strategies for functional cargo-loading. Three distinct types of adipose mesenchymal stem cells-derived EVs (ADSCs-EVs) are successfully isolated utilizing 3D culture platforms consisting of porous gelatin methacryloyl (PG), PG combined with sericin methacryloyl (PG/SerMA), or PG combined with chondroitin sulfate methacryloyl (PG/ChSMA). These correspond to PG-EVs, PG/SerMA-EVs, and PG/ChSMA-EVs, respectively. Unique microRNA (miRNA) profiles are observed in each type of ADSCs-EVs. Notably, PG-EVs encapsulate higher levels of hsa-miR-455-3p and deliver more hsa-miR-455-3p to chondrocytes, which results in the activation of the hsa-miR-455-3p/PAK2/Smad2/3 axis and the subsequent hyaline cartilage regeneration. Furthermore, the functionality of PG-EVs is optimized through engineered strategies, including agomir/lentivirus transfection, electroporation, and Exo-Fect transfection. These strategies, referred to as Agomir-EVs, Lentivirus-EVs, Electroporation-EVs, and Exo-Fect-EVs, respectively, are ranked based on their efficacy in encapsulating hsa-miR-455-3p, delivering hsa-miR-455-3p to chondrocytes, and promoting cartilage formation via the hsa-miR-455-3p/PAK2/Smad2/3 axis. Notably, Exo-Fect-EVs exhibit the highest efficiency. Collectively, the 3D culture conditions and engineered strategies have an impact on the miRNA profiles and cartilage regeneration capabilities of ADSCs-EVs. The findings provide valuable insights into the mechanisms underlying the promotion of cartilage regeneration by ADSCs-EVs.

Characterization of the pheromone receptors in Mythimna loreyi reveals the differentiation of sex pheromone recognition in Mythimna species.

Pheromone receptors (PRs) are key proteins in the molecular mechanism of pheromone recognition, and exploring the functional differentiation of PRs between closely related species helps to understand the evolution of moth mating systems. Pheromone components of the agricultural pest Mythimna loreyi have turned into (Z)-9-tetradecen-1-yl acetate (Z9-14:OAc), (Z)-7-dodecen-1-yl acetate (Z7-12:OAc), and (Z)-11-hexadecen-1-yl acetate, while the composition differs from that of M. separata in the genus Mythimna. To understand the molecular mechanism of pheromone recognition, we sequenced and analyzed antennal transcriptomes to identify 62 odorant receptor (OR) genes. The expression levels of all putative ORs were analyzed using differentially expressed gene analysis. Six candidate PRs were quantified and functionally characterized in the Xenopus oocytes system. MlorPR6 and MlorPR3 were determined to be the receptors of major and minor components Z9-14:OAc and Z7-12:OAc. MlorPR1 and female antennae (FA)-biased MlorPR5 both possessed the ability to detect pheromones of sympatric species, including (Z,E)-9,12-tetradecadien-1-ol, (Z)-9-tetradecen-1-ol, and (Z)-9-tetradecenal. Based on the comparison of PR functions between M. loreyi and M. separata, we analyzed the differentiation of pheromone recognition mechanisms during the evolution of the mating systems of 2 Mythimna species.

The association of personality traits with childhood obesity: A systematic review and meta-analysis.

BACKGROUND: A growing body of evidence has revealed an association between personality traits and obesity, but the findings regarding this association among children remain mixed. The aim of this review was to systematically summarize the literature regarding the associations between personality traits and childhood obesity. METHODS: The study has been registered on PROSPERO (CRD42022306529). We searched a total of 8 databases up to July 1, 2023, to identify both published studies and grey literature written in English. Personality traits were classified into five dimensions based on the widely used Five-Factor Model. We conducted random effects meta-analyses to quantitatively synthesize the data. Newcastle-Ottawa Scale was used to assess the quality of included studies. RESULTS: A total of 7 studies were included. The pooled correlation coefficient of 2 studies was -0.09 (95 % CI: -0.17 to 0.00; I2 = 0 %) and the pooled standardized mean difference of 3 studies was -0.08 (95 % CI: -0.13 to -0.03; I2 = 66 %), indicating that conscientiousness was negatively associated with childhood obesity. No consistent patterns were found in the associations between the other 4 dimensions of personality traits and BMI/obesity in children. LIMITATIONS: Our findings should be interpreted with caution due to the exclusion of non-English studies, the limited generalizability to Eastern population, and the scarcity body of evidence for present topic. CONCLUSIONS: Low conscientiousness has been found to be consistently associated with childhood obesity. Causal associations of personality traits with the risk of childhood obesity remain to be clarified in future studies.

The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility.

PIWI-clade proteins harness piRNAs of 24-33 nt in length. Of great puzzles are how PIWI-clade proteins incorporate piRNAs of different sizes and whether the size matters to PIWI/piRNA function. Here we report that a PIWI-Ins module unique in PIWI-clade proteins helps define the length of piRNAs. Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter piRNAs and causes spermiogenic failure in mice, demonstrating the functional importance of this regulatory module. Mechanistically, we show that longer piRNAs provide additional complementarity to target mRNAs, thereby enhancing the assembly of the MIWI/eIF3f/HuR super-complex for translational activation. Importantly, we identify a c.1108C>T (p.R370W) mutation of HIWI (human PIWIL1) in infertile men and demonstrate in Miwi knock-in mice that this genetic mutation impairs male fertility by altering the property of PIWI-Ins in selecting longer piRNAs. These findings reveal a critical role of PIWI-Ins-ensured longer piRNAs in fine-tuning MIWI/piRNA targeting capacity, proven essential for spermatid development and male fertility.

Functional characterization of pheromone receptor candidates in codling moth Cydia pomonella (Lepidoptera: Tortricidae).

Sex pheromones serve a critical role in Lepidopterans finding mates. Male moths perceive and react to sex pheromones emitted by conspecific females through a delicate pheromone communication system. Pheromone receptors (PRs) are the key sensory elements at the beginning of that process. The codling moth (Cydia pomnonella) is an important pome fruit pest globally and a serious invasive species in China. Pheromone-based techniques have been used successfully in monitoring and controlling this species. We conducted ribonucleic acid sequencing analysis of the codling moth antennal transcriptome and identified 66 odorant receptors (ORs) in a population from Xinjiang province, China, of which 14 were PRs, including two novel PRs (CpomOR2e and CpomOR73). Four PRs that contain full-length open reading frames (CpomOR1, OR2a, OR5, OR7) and four PRs with ligands that have not been reported previously (CpomOR1, OR2a, OR5, OR7) were selected to deorphanize in the heterologous Xenopus oocyte expression system. Specifically, we found that CpomOR2a and CpomOR5 responded to (E,E)-8, 10-dodecadien-1-yl acetate (codlemone acetate). Furthermore, CpomOR5 (EC50 = 1.379 × 10-8 mol/L) was much more sensitive to codlemone acetate than CpomOR2a (EC50 = 1.663 × 10-6 mol/L). Since codlemone acetate is an important component of C. pomonella sex pheromone, our results improve the current understanding of pheromone communication in codling moths and will be helpful for the development of pest management strategies.

Scar-reducing effects of gambogenic acid on skin wounds in rabbit ears.

Hypertrophic scar (HS) is a dermal fibroproliferative disease that often occurs following abnormal wound healing. To date, there is no satisfied treatment strategies for improvement of scar formation with few side effects. The effects of gambogenic acid (GNA) on scar hypertrophy has not been studied previously. The present study was undertaken to find out the scar-reducing effects of GNA (0.48, 0.96 or 1.92 mg/ml) on skin wounds in rabbit ears. Scar evaluation index (SEI), collagen I (Col1) and collagen III (Col3), microvascular density (MVD), CD4+T cells and macrophages, vascular endothelial growth factor receptor 2 (VEGFR2), fibroblast growth factor receptor 1 (FGFR1), phospho-VEGFR 2 (p-VEGFR2) and p-FGFR1, interleukin (IL)-1ß, IL-6, IL-10 and tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1 and connective tissue growth factor (CTGF) in scar tissue were detected using various methods, respectively. Our data showed that GNA significantly reduced SEI, and the expression of Col1 and Col3 in scar tissue in a concentration-dependent manner. Also, it decreased MVD, the infiltration of CD4+T cells and macrophages, and the levels of VEGFR2, p-VEGFR2, FGFR1, p-FGFR1, TGF-ß1, CTGF, IL-1ß, IL-6, TNF-α, in addition to upregulated IL-10 in scar tissue. As a result, this study revealed that GNA reduced HS formation, which was associated with the inhibition of neoangiogenesis, local inflammatory response and growth factor expression in scar tissue during wound healing. These findings suggested that GNA may be considered as a preventive and therapeutic candidate for HS.

Effects of sorafenib on fibroblast-like synoviocyte apoptosis in rats with adjuvant arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by synovial inflammation and hyperplasia resulting from an imbalance between the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs). Our previous study found that sorafenib had inhibitory effects in rats with adjuvant arthritis (AA). The present study investigated the role of sorafenib in the induction of AA FLS apoptosis in vitro. FLSs obtained from AA rats were cultured in vitro and identified. Cell apoptosis was detected using terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) labeling methods. Real-time PCR and Western blotting assays were used to quantify the expression levels of Fas, Caspase-3, Mcl-1, NF-κB and C-jun gene products in AA FLSs. Our data revealed that sorafenib (4 µmol/L) induced apoptosis in AA FLSs, and flow cytometry analysis showed that AA FLSs treated with sorafenib (4 µmol/L) in vitro accumulated in early and late apoptosis. There were significant increases in the expression levels of Fas, Caspase-3 and Mcl-1, and significant decreases in NF-κB and C-jun expression in AA FLSs treated with sorafenib. In summary, these results demonstrate that sorafenib promotes AA FLS apoptosis, which may be related to the upregulation of Fas and Caspase-3 and downregulation of NF-κB and C-jun. All of these findings suggest that sorafenib exerts an inhibitory effect on AA rats in vivo via AA FLS apoptotic induction, which has potential therapeutic implications for RA.

[Characteristics of humidity and temperature variations and CO2 exchange of mobile dunes at different space-time scales in Horqin sandy land, China].

Terrestrial carbon cycle plays a key role in driving climate change and ecosystem carbon balance. Understanding the variations of humidity and temperature and CO2 exchanges are meaningful to reveal the law and mechanism of regional carbon cycles in deserts. We examined the near surface humidity, temperature variations, and CO2 exchanges by eddy covariance and Bowen ratio systems in a typical mobile dune of Horqin sandy land. We analyzed the relationships between water-heat and CO2 exchanges of 0 to 10 m vertical height at daily and seasonal scales were analyzed. The results showed that the vertical variations of near surface temperature ranged from 0.4 ℃ to 2 ℃ and decreased with the increases of height from April to September, but with an opposite pattern in other months. The seasonal variation of air relative humidity was greater than 40%. During the growing season of 2018, the averaged daily net ecosystem carbon exchange (NEE) was -0.02 mg·m-2·s-1. The annual averaged daily NEE was 0.003 mg·m-2·s-1, indicating that the mobile dunes were carbon sources at the whole year scale. The vertical differences of temperature and humidity well fitted the NEE. The inflexion points of the fitting curve were at 10% humidity and 0.5 ℃ temperature, respectively. At the scalem of the year, the NEE fitting result of temperature was better than that of humidity, with the inflexion points at 17 ℃ and 65% humidity, respectively. In the growing season, the near surface vertical temperature difference was negative, which would inhibit CO2 absorption of mobile dunes. The circumstances of high humidity would promote the absorption of atmospheric CO2. Across different time and vertical height, the variations of humidity and temperature were closely related to CO2 exchanges, which affected carbon sink and source of mobile dunes. Carbon budget was more sensitive to temperature than humidity.

Antiarthritic Effects of Sorafenib in Rats with Adjuvant-Induced Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane of joints. In this study, we aimed to investigate whether sorafenib exerts antiarthritic effects on RA in vivo. Adjuvant arthritis (AA) was induced (day 0) in male Sprague-Dawley rats by intradermal injection of 0.1 mL of complete Freund's complete adjuvant into the left hind paw. Sorafenib (10, 20, or 40 mg/kg/day) was administered intragastrically from day 10 to 24. Body weight, paw volume, synovial inflammation, and tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-10, and IL-17 serum levels were detected. In addition, microvascular density (MVD) and the expression of vascular endothelial growth factor receptor 2 (VEGFR-2) and fibroblast growth factor receptor 1 (FGFR-1) in synovial tissues were analyzed. Our data revealed that sorafenib administration led to significant body weight gain in AA rats but suppressed paw swelling, synovial hyperplasia, and inflammatory infiltration. Furthermore, it decreased TNF-α, IL-1ß, and IL-17 serum levels and upregulated IL-10. MVD and VEGFR-2 and FGFR-1 expression in synovial tissues were significantly reduced. Thus, this study shows that sorafenib exerts anti-arthritic effects in AA rats and therefore has potential in RA treatment. Anat Rec, 301:1519-1526, 2018. © 2018 Wiley Periodicals, Inc.

Effect of recombinant human endostatin on hypertrophic scar fibroblast apoptosis in a rabbit ear model.

Hypertrophic scar (HS) is a dermal fibroproliferative disorder characterized by the excessive proliferation of fibroblasts and is thought to result from a cellular imbalance caused by the increased growth and reduced apoptosis of hypertrophic scar fibroblasts (HSFs). Our recent study demonstrated that recombinant human endostatin (rhEndostatin) plays a key role in the inhibition of HSF proliferation in vitro, with a resulting decrease in dermal thickness and scar hypertrophy. However, the effect of this protein on HSF apoptosis is unknown. The present study was undertaken to directly examine the effect of rhEndostatin on HSF apoptosis in the rabbit ear model. Transmission electron microscopy and flow cytometry were used to investigate HSF apoptosis in scar tissues and cultured HSFs in vitro, respectively. The expression levels of the c-jun, c-fos, NF-κB, fas, caspase-3, and bcl-2 gene products in HSFs were quantified using real-time PCR and Western blotting assays. Our data reveal that rhEndostatin (2.5 or 5mg/ml) induces HSF apoptotic cell death in scar tissue. Additionally, HSFs treated with rhEndostatin (100mg/L) in vitro accumulated in early and late apoptosis and displayed significantly decreased expression of c-jun, c-fos, NF-κB, fas, caspase-3 and bcl-2. In sum, these results demonstrate that rhEndostatin induces HSF apoptosis, and this phenotypeis partially due to downregulation of NF-κB and bcl-2. These findings suggest that rhEndostatin may have an inhibitory effect on scar hypertrophy in vivo via HSF apoptotic induction and therefore has potential therapeutic use for the treatment of HS.