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Intracellular bacterial infections pose enormous challenges to food safety and public health. Antibiotic-based polymer prodrugs have been used to treat intracellular bacterial infection. However, the overuse of antibiotics may lead to the emergence of antibiotic resistance. In this work, we aimed to develop antibiotic-free pH-responsive polymeric prodrugs to combat intracellular S. aureus infection. Amphiphilic poly(ethylene glycol)-b-poly[(3-phenylprop-2-ene-1,1-diyl)bis(oxy)bis(enthane-2,1- diyl)diacrylate] (PEG-b-PCAE) was obtained by radical polymerization and they could self-assemble to form micelles. PEG-b-PCAE micelles could uptake by macrophage. Upon exposure to the acidic phagolysosome, PEG-b-PCAE micelles could release cinnamaldehyde (CA) through hydrolysis of the acetal linkage. PEG-b-PCAE could kill intracellular bacteria by damaging the bacterial membrane. Furthermore, PEG-b-PCAE micelles could generate reactive oxygen species (ROS) in macrophages and subsequently activate immune system to clear bacteria by inducing macrophages differentiation to M1 phenotype. PEG-b-PCAE micelles could accelerate the wound healing process of the S. aureus-infected model in vivo. It is anticipated that multifunctional antibiotic-free PEG-b-PCAE micelles with intrinsic antibacterial activities hold promise for improved outcomes in intracellular S. aureus infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Ticks are hematophagous parasites that transmit an extensive range of pathogens to their vertebrate hosts. Ticks can destroy invading microorganisms or alleviate infection via their rudimentary but orchestrated innate immune system. Antimicrobial peptides (AMPs) are important components of tick innate immunity. Among these humoral effector molecules, defensins are well-studied and widely identified in various species of Ixodidae (hard ticks) and Argasidae (soft ticks). This review was aimed at presenting the characterization of tick defensins from structure-based taxonomic status to antimicrobial function., Main Text: All published papers written in English from 2001 to May 2022 were searched through PubMed and Web of Science databases with the combination of relevant terms on tick defensins. Reports on identification and characterization of tick defensins were included. Of the 329 entries retrieved, 57 articles were finally eligible for our scoping review. Tick defensins mainly belong to the antibacterial ancient invertebrate-type defensins of the cis-defensins superfamily. They are generally small, cationic, and amphipathic, with six cysteine residues forming three intra-molecular disulfide bonds. Tick defensins primarily target membranes of a variety of pathogens, including Gram-positive and Gram-negative bacteria, fungi, viruses, and protozoa. Since tick defensins have a high degree of variability, we summarize their common biological properties and enumerate representative peptides. Along with the various and potent antimicrobial activities, the role of tick defensins in determining vector competence is discussed., Conclusions: Due to their broad-spectrum antimicrobial activities, tick defensins are considered novel candidates or targets for controlling infectious diseases., (© 2022. The Author(s).)

Long non-coding (lnc) RNA plays important roles in many cellular processes. The function of the vast majority of lncRNAs remains unknown. Here we identified that lncRNA-1700113A16RIK existed in skeletal muscle stem cells (MuSCs) and was significantly elevated during MuSC differentiation. Knockdown of 1700113A16RIK inhibits the differentiation of muscle stem cells. In contrast, overexpression of 1700113A16RIK promotes the differentiation of muscle stem cells. Further study shows the muscle specific transcription factor Myogenin (MyoG) positively regulates the expression of 1700113A16RIK by binding to the promoter region of 1700113A16RIK. Mechanistically, 1700113A16RIK may regulate the expression of myogenic genes by directly binding to 3'UTR of an important myogenic transcription factor MEF2D, which in turn promotes the translation of MEF2D. Taken together, our results defined 1700113A16RIK as a positive regulator of MuSC differentiation and elucidated a mechanism as to how 1700113A16RIK regulated MuSC differentiation., (© 2022. The Author(s).)

Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells (BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2 (Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling. RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging., (© 2022. The Author(s).)

Glucose is a primary source of energy used in most organisms. Thus, development of reliable approaches to measure intracellular glucose uptake is an important research issue. 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG), as a fluorescent glucose derivative, has been widely used to track intracellular glucose uptake by fluorescence imaging and measuring in mammalian cells. However, the avoid-less cross-interference of intrinsic autofluorescence background and tested fluorescent compounds limits its ability to provide trustworthy information on intracellular glucose uptake. By the extraction, separation and detection of 2-NBDG, a simple, sensitive and accurate HPLC-FLD method was established and validated for the measurement of intracellular glucose uptake in HepG2 cells. The developed method has been employed successfully to assess the glucose uptake activity of anti-diabetic drugs and fluorescent natural products. A fit-for-purpose partial validation was further performed for quantification and comparison of glucose uptake in AML12, LO2 hepatocytes, L6 myoblasts and 3T3-L1 preadipocytes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Maintaining proteostasis is important for animal development. How proteostasis influences spermatogenesis that generates male gametes, spermatozoa, is not clear. We show that testis-specific paralog of ribosomal large subunit protein RPL39, RPL39L, is required for mouse spermatogenesis. Deletion of Rpl39l in mouse caused reduced proliferation of spermatogonial stem cells, malformed sperm mitochondria and flagella, leading to sub-fertility in males. Biochemical analyses revealed that lack of RPL39L deteriorated protein synthesis and protein quality control in spermatogenic cells, partly due to reduced biogenesis of ribosomal subunits and ribosome homeostasis. RPL39/RPL39L is likely assembled into ribosomes via H/ACA domain containing NOP10 complex early in ribosome biogenesis pathway. Furthermore, Rpl39l null mice exhibited compromised regenerative spermatogenesis after chemical insult and early degenerative spermatogenesis in aging mice. These data demonstrate that maintaining proteostasis is important for spermatogenesis, of which ribosome homeostasis maintained by ribosomal proteins coordinates translation machinery to the regulation of cellular growth., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Background: Jinqi Jiangtang (JQJT) has been widely used in clinical practice to prevent and treat type 2 diabetes. However, little research has been done to identify and classify its quality markers (Q-markers) associated with anti-diabetes bioactivity. In this study, a strategy combining mass spectrometry-based untargeted metabolomics with backpropagation artificial neural network (BP-ANN)-based machine learning approach was proposed to screen Q-markers from JQJT preparation., Methods: This strategy mainly involved chemical profiling of herbal medicines, statistic processing of metabolomic datasets, detection of different anti-diabetes activities and establishment of BP-ANN model. The chemical features of seventy-eight batches of JQJT extracts were first profiled by using the untargeted UPLC-LTQ-Orbitrap metabolomic approach. The chemical features obtained which were associated with different anti-diabetes activities based on three modes of action were normalized, ranked, and then pre-selected by using ReliefF feature selection. BP-ANN model was then established and optimized to screen Q-markers based on mean impact value (MIV)., Results: Optimized BP-ANN architecture was established with high accuracy of R > 0.9983 and relative low error of MSE < 0.0014, which showed better performance than that of partial least square (PLS) model (R 2  < 0.5). Meanwhile, the BP-ANN model was subsequently applied to further screen potential bioactive components from the pre-selected chemical features by calculating their MIVs. With this machine learning model, 10 potential Q-markers with bioactivity were discovered from JQJT. The tested anti-diabetes bioactivities of 78 batches of JQJT could be accurately predicted., Conclusions: This proposed artificial intelligence approach is desirable for quick and easy identification of Q-markers with bioactivity from JQJT preparation.

Two metal-organic frameworks (MOFs), namely, [Ni(DTP)(H 2 O)] n (I) and [Cd 2 (DTP) 2 (bibp) 1.5 ] n (II) (H 2 DPT = 4'-(4-(3,5-dicarboxylphenoxy) phenyl)-4,2':6',4″-terpyridine; bibp = 1,3-di(1H-imidazol-1-yl)propane), that present structural diversity were solvothermally prepared. Single-crystal X-ray diffraction analysis indicates that they consist of {NiN 2 O 4 } building units (for I) and {CdO 4 N 2 } and {CdO 3 N 3 } building units (for II), which are further linked by multicarboxylate H 2 DPT to construct microporous three-dimensional frameworks. The remarkable character of these frameworks is that coordination polymer II demonstrates highly selective and sensitive bifunctional luminescent sensor toward nitrobenzene and Cu 2+ ion. The fluorescence quenching mechanism of II caused by nitrobenzene is ascribed to electron transfer from electron-rich (II) to electron-deficient nitrobenzene. The result was also evidenced by the density functional theory. Furthermore, anti-ferromagnetic as well as electrochemical characters of Ni-MOF (I) were also investigated in this paper.

Termites are well recognized for their thriving on recalcitrant lignocellulosic diets through nutritional symbioses with gut-dwelling microbiota; however, the effects of diet changes on termite gut microbiota are poorly understood, especially for the lower termites. In this study, we employed high-throughput 454 pyrosequencing of 16S V1-V3 amplicons to compare gut microbiotas of Tsaitermes ampliceps fed with lignin-rich and lignin-poor cellulose diets after a 2-week-feeding period. As a result, the majority of bacterial taxa were shared across the treatments with different diets, but their relative abundances were modified. In particular, the relative abundance was reduced for Spirochaetes and it was increased for Proteobacteria and Bacteroides by feeding the lignin-poor diet. The evenness of gut microbiota exhibited a significant difference in response to the diet type (filter paper diets < corn stover diets < wood diets), while their richness was constant, which may be related to the lower recalcitrance of this biomass to degradation. These results have important implications for sampling and analysis strategies to probe the lignocellulose degradation features of termite gut microbiota and suggest that the dietary lignocellulose composition could cause shifting rapidly in the termite gut microbiota.

Objective: To investigate the role of reducing resistance and distraction in rapid teeth movement and its reliability by establishing the Beagle dogs' experimental model., Methods: The left or right sides in mandibles of 20 beagles were randomly operated with different treatments: distraction twice a day through reducing resistance; distraction 6 times a day through reducing resistance; conventional distraction through reducing resistance; and conventional distraction (the control group). Each treatment was carried out in 10 sides. The pulp vitality, tooth mobility and distance of teeth transportation were evaluated at different time points: before the distraction, distraction after 15 days, retaining 30 days after 15 days of distraction. The degree of inclination, root resorption and alveolar bone density of the compressive areas were evaluated by cone-beam computed tomography images., Results: The distance of teeth transportation was similar in groups distraction twice daily and 6 times a day through reducing resistance (P>0.05), but their speed of transportation was significantly higher than that of conventional distraction through reducing resistance. The conventional distraction group had the lowest speed of transportation. The pulp vitality of distracted teeth was normal, and no root comprehensive resorption and periodontal defect were found. Distracted teeth in the reduced resistance and distraction groups (13.9°±3.5°) tipped more that in the conventional distraction group (6.6°±1.3°) (P<0.05)., Conclusion: Reducing resistance and distraction are inseparable factors to realize fast teeth moving. The rate of orthodontic tooth movement can be accelerated through resistance reduction and periodontal distraction without obvious unfavorable effects but at minimal acceptable teeth inclination.

Objective: To evaluate the effect of rapid teeth movement through reducing resistance and distraction using cone-beam computed tomography (CBCT)., Methods: The left or right side of the mandible of 10 beagles (5 males and 5 females) was randomly selected as the control side (for the conventional distraction with a force of about 85 g) and the other side as the experimental side (subjected to reducing resistance and distraction). CBCT images were taken at 5, 10, and 15 days and also after retaining for 10 and 90 days after distraction for 15 days. The distance of teeth transportation, degree of inclination, alveolar bone density of the compressive area and root resorption were evaluated based on the CBCT images and Ez3D2009 visualization software., Results: No significant difference was found between CBCT-based measurement and direct measurement of teeth transportation distance within the mouths (P>0.05). Teeth inclination on the experimental side was slightly greater than that on the control side (P<0.05). The root resorption on the experimental side was minimal, and the bone density increased gradually along with the teeth migration. The experimental side showed a comparable newly formed alveolar bone density and similar X-ray features of the compressive area with the control side., Conclusions: CBCT three-dimensional imaging can resolve the problems of overlapping and deformation of the two-dimensional images and is especially useful for measurement of teeth inclination and alveolar bone density in the process of reducing resistance and distraction.

Mammalian spermatogenesis originates from spermatogonial stem cells (SSCs), which undergo mitosis, meiosis and spermiogenesis in order to generate mature spermatozoa. SSCs are adult stem cells that can both self-renew and differentiate. To maintain pluripotency, SSCs are regulated by both extrinsic factors secreted from surrounding somatic cells and intrinsic factors including specific gene expression programs. Using fluorescent labeled germ line stem cells, mouse gonocytes and SSCs were purified up to 97% by improved FACS method. Through microarray analyses, global gene expression profiles of gonocytes, SSCs, and differentiated cells were compared. A large number of distinctive genes were found to be enriched in respective cell populations, indicating different functional requirements of each cell type. Functional clustering analyses revealed that while gonocytes and SSCs preferentially express genes implicated in gene expression regulation and epigenetic modifications, differentiated cells including somatic cells are enriched with genes encoding proteins involved in various cellular activities. Further in situ hybridization and RT-PCR experiments confirmed SSC specific expression of several genes of which functions have not been characterized in SSCs. The comparative gene expression profiling provides a useful resource for gene discovery in relation to SSC regulation and opens new avenues for the study of molecular mechanisms underlying SSC self-renewal and differentiation., (Copyright © 2012 Wiley Periodicals, Inc.)