IFN-stimulated metabolite transporter ENT3 facilitates viral genome release.

An increasing amount of evidence emphasizes the role of metabolic reprogramming in immune cells to fight infections. However, little is known about the regulation of metabolite transporters that facilitate and support metabolic demands. In this study, we found that the expression of equilibrative nucleoside transporter 3 (ENT3, encoded by solute carrier family 29 member 3, Slc29a3) is part of the innate immune response, which is rapidly upregulated upon pathogen invasion. The transcription of Slc29a3 is directly regulated by type I interferon-induced signaling, demonstrating that this metabolite transporter is an interferon-stimulated gene (ISG). Suprisingly, we unveil that several viruses, including SARS-CoV-2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of Slc29a3 expression is sufficient to significantly decrease viral replication in vitro and in vivo. Our study reveals that ENT3 is a pro-viral ISG co-opted by some viruses to gain a survival advantage.

The impact of tissue glue in wound healing of head and neck patients undergoing neck dissection.

We investigated the impact of fibrin glue on postoperative drainage amount and duration in head and neck cancer patients who underwent neck dissection. This study was a prospective randomized controlled trial. Patients who were scheduled to undergo neck dissection due to head and neck cancer were eligible for this study. After receiving a detailed explanation, all patients signed an informed consent form before enrollment. Patients were then randomly assigned to the study group (fibrin glue) or control group. In the study group, 2 ml of fibrin glue (Tissucol(®); Duploject, Baxter AG) was applied on the surface of the surgical wound before closure. Basic demographic data along with tumor-related features, operation-related variables, postoperative drainage amount/duration, postoperative pain, and analgesic usage were collected and analyzed. A total of 15 patients were included in the final analyses, with eight patients in the study group and seven patients in the control group. No significant differences were found between the two groups in age, gender, primary site, clinical N stage, neck dissection levels, perioperative bleeding, postoperative drainage amount/duration, hospitalization duration, and postoperative pain status. The application of 2 ml fibrin glue by the method described herein did not reduce the postoperative drainage amount/duration nor the postoperative pain status in patients who underwent neck dissection.

Protective effect of ethanolic extract of Echinacea purpurea contained nanoparticles on meniscal/ligamentous injury induced osteoarthritis in obese male rats.

Osteoarthritis (OA) is a chronic degenerative joint disease associated with age, mechanical stress, and obesity. Echinacea purpurea is a medicinal plant that shows good anti-inflammatory, antioxidant, and immunomodulatory activities. In this study, Echinacea purpurea ethanol extract nanoparticles (Nano-EE) were prepared by encapsulating Echinacea purpurea ethanol extract (EE) in chitosan-silica nanoparticles. Obesity (OB) in Sprague-Dawley (SD) rats was induced by fed 40% high-fat diet and then anterior cruciate ligament and meniscus injury were performed to induce OA. The rats got different doses of samples by oral gavage. The encapsulation efficiency and loading capacity of Nano-EE were 69.1% and 36.1%, respectively. The average size, polydispersity index (PDI), and zeta potential (ZP) of the Nano-EE were 145 ± 11 nm, 0.24 ± 0.01, - 4.57 ± 0.44 mV, respectively. Furthermore, electron microscopic images showed that the particles were spherical and were slightly agglomerated. Moreover, it showed that the leptin content, expression of MMPs, cytokines level, NF-κB level, and iNOS production were decreased whereas collagen II expression was increased after treatment. Besides, Nano-EE ameliorated the pain caused by OA and reduced the proteoglycan loss in cartilage. These results indicated that encapsulated EE (Nano-EE) can ameliorate OA with a low dosage and are more effective than unencapsulated EE.

Multiomics reveal the central role of pentose phosphate pathway in resident thymic macrophages to cope with efferocytosis-associated stress.

Tissue-resident macrophages (TRMs) are heterogeneous cell populations found throughout the body. Depending on their location, they perform diverse functions maintaining tissue homeostasis and providing immune surveillance. To survive and function within, TRMs adapt metabolically to the distinct microenvironments. However, little is known about the metabolic signatures of TRMs. The thymus provides a nurturing milieu for developing thymocytes yet efficiently removes those that fail the selection, relying on the resident thymic macrophages (TMφs). This study harnesses multiomics analyses to characterize TMφs and unveils their metabolic features. We find that the pentose phosphate pathway (PPP) is preferentially activated in TMφs, responding to the reduction-oxidation demands associated with the efferocytosis of dying thymocytes. The blockade of PPP in Mφs leads to decreased efferocytosis, which can be rescued by reactive oxygen species (ROS) scavengers. Our study reveals the key role of the PPP in TMφs and underscores the importance of metabolic adaptation in supporting Mφ efferocytosis.

Eleven generations of selection for the duration of fertility in the intergeneric crossbreeding of ducks.

A 12-generation selection experiment involving a selected line (S) and a control line (C) has been conducted since 1992 with the aim of increasing the number of fertile eggs laid by the Brown Tsaiya duck after a single artificial insemination (AI) with pooled Muscovy semen. On average, 28.9% of the females and 17.05% of the males were selected. The selection responses and the predicted responses showed similar trends. The average predicted genetic responses per generation in genetic standard deviation units were 0.40 for the number of fertile eggs, 0.45 for the maximum duration of fertility, and 0.32 for the number of hatched mule ducklings' traits. The fertility rates for days 2-8 after AI were 89.14% in the S line and 61.46% in the C line. Embryo viability was not impaired by this selection. The largest increase in fertility rate per day after a single AI was observed from d5 to d11. In G12, the fertility rate in the selected line was 91% at d2, 94% at d3, 92% at days 3 and 4 then decreased to 81% at d8, 75% at d9, 58% at d10 and 42% at d11. In contrast, the fertility rate in the control line showed an abrupt decrease from d4 (74%). The same tendencies were observed for the evolution of hatchability according to the egg set rates. It was concluded that selection for the number of fertile eggs after a single AI with pooled Muscovy semen could effectively increase the duration of the fertile period in ducks and that research should now be focused on ways to improve the viability of the hybrid mule duck embryo.

Automated tongue diagnosis on the smartphone and its applications.

Tongue features are important objective basis for clinical diagnosis and treatment in both western medicine and Chinese medicine. The need for continuous monitoring of health conditions inspires us to develop an automatic tongue diagnosis system based on built-in sensors of smartphones. However, tongue images taken by smartphone are quite different in color due to various lighting conditions, and it consequently affects the diagnosis especially when we use the appearance of tongue fur to infer health conditions. In this paper, we captured paired tongue images with and without flash, and the color difference between the paired images is used to estimate the lighting condition based on the Support Vector Machine (SVM). The color correction matrices for three kinds of common lights (i.e., fluorescent, halogen and incandescent) are pre-trained by using a ColorChecker-based method, and the corresponding pre-trained matrix for the estimated lighting is then applied to eliminate the effect of color distortion. We further use tongue fur detection as an example to discuss the effect of different model parameters and ColorCheckers for training the tongue color correction matrix under different lighting conditions. Finally, in order to demonstrate the potential use of our proposed system, we recruited 246 patients over a period of 2.5 years from a local hospital in Taiwan and examined the correlations between the captured tongue features and alanine aminotransferase (ALT)/aspartate aminotransferase (AST), which are important bio-markers for liver diseases. We found that some tongue features have strong correlation with AST or ALT, which suggests the possible use of these tongue features captured on a smartphone to provide an early warning of liver diseases.

Miconazole induces apoptosis via the death receptor 5-dependent and mitochondrial-mediated pathways in human bladder cancer cells.

Miconazole (MIC), an antifungal agent, diplays anti­tumorigenic activity in various types of human cancers, including bladder cancer, yet its mechanism of antitumor action is not well understood. In the present study, we demonstrated that, in a cell viability assay, MIC had a cytotoxic effect on human T24, J82 and TSGH-8301 bladder cancer cells in a dose- and time­dependent manner, but did not exhibit significant toxicity toward human peripheral blood mononuclear cells. Cell cycle analysis revealed that MIC at concentrations of 25 and 50 µM significantly caused G0/G1 arrest in the TSGH-8301 and T24 cells, respectively. DNA fragmentation, mitochondrial membrane potential and western blot analyses showed that MIC inhibited the growth of these cells by both mitochondrial­mediated and death receptor (DR5)­mediated apoptosis pathways. Specifically, MIC increased the protein levels of p21 and p27, but decreased the expression of cyclin E1, CDK2 and CDK4. MIC augmented the expression of DR5, cleaved forms of caspase-3 -8 and -9, poly(ADP­ribose) polymerase and Bax, decreased the expression of Bcl-2 but increased cytosol levels of cytochrome c. Our results suggest that MIC inhibits the growth of bladder cancer cells through induction of G0/G1 arrest and apoptosis via activation of both the extrinsic and intrinsic apoptotic pathways. MIC is a potential chemotherapeutic agent for treating bladder cancer in humans.

Genomic organization of the chicken CD8 locus reveals a novel family of immunoreceptor genes.

The genomic organization of the chicken CD8alpha gene was investigated to determine the basis of its polymorphism. Contiguous to the CD8alpha gene we identified multiple DNA blocks possessing sequences homologous to CD8alpha. Gene conversions and recombination over evolutionary time among CD8alpha and these CD8alpha homologous genes seem to account for the observed polymorphism. Furthermore, these CD8alpha-like DNAs encode a distinct multigene family of immunoreceptors that have a charged or polar residue in place of the interspecies-conserved CD8alpha transmembrane proline residue and a short cytoplasmic tail nonhomologous to CD8alpha. The identification of this novel multigene family with an organization reminiscent of human killer Ig-like receptors raises compelling questions on their evolutionary relationship among immunoreceptors.