OBJECTIVE: To summarize the research progress of rodent models of secondary lymphedema (SL) and provide a reference for selecting appropriate animal models in SL research. METHODS: Recent literature on rodent SL models at home and abroad was comprehensively analyzed, summarizing model categories, development techniques, strengths, and weaknesses. RESULTS: Current research primarily utilizes rats and mice to establish SL models. The main model types include hind limb, forelimb, tail, and head/neck models. The hind limb model is the most frequently employed, typically requiring surgery combined with irradiation to induce stable chronic edema. Forelimb models primarily simulate upper limb lymphedema, but exhibit relatively rapid edema resolution. Tail models offer operational simplicity and are predominantly used for studying acute edema mechanisms and interventions; however, they demonstrate poor clinical relevance. Emerging head/neck models provide a valuable tool for investigating head and neck cancer-associated lymphedema. These models exhibit variations in lymphedema duration, degree of fibrosis, and edema incidences. CONCLUSION Existing models still fall short in faithfully replicating the chronicity, fibrosis, fat deposition, and complex microenvironment characteristic of human chronic lymphedema. Future research must integrate multidisciplinary approaches, optimize model construction strategies, and explore novel modeling approaches to more accurately mimic the human disease and advance SL prevention and treatment research.
Lymphedema/pathology* ; Animals ; Disease Models, Animal ; Rats ; Mice ; Humans ; Head and Neck Neoplasms/complications* ; Rodentia

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Phosphatidylinositol 3-Kinase/metabolism* ; Facial Nerve Injuries/therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Beclin-1 ; Glial Cell Line-Derived Neurotrophic Factor ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Mammals/metabolism*

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals ; Mice ; Humans ; Ependymoglial Cells/metabolism* ; Hedgehog Proteins/metabolism* ; Ferrets/metabolism* ; Cerebral Cortex ; Neurogenesis ; Mammals/metabolism* ; Neuroglia/metabolism* ; Bone Morphogenetic Protein 7/metabolism*

Spermatogenesis is a continual process that occurs in the testes, in which diploid spermatogonial stem cells (SSCs) differentiate and generate haploid spermatozoa. This highly efficient and intricate process is orchestrated at multiple levels. N⁶-methyladenosine (m⁶A), an epigenetic modification prevalent in mRNAs, is implicated in the transcriptional regulation during spermatogenesis. However, the dynamics of m⁶A modification in non-rodent mammalian species remains unclear. Here, we systematically investigated the profile and role of m⁶A during spermatogenesis in pigs. By analyzing the transcriptomic distribution of m⁶A in spermatogonia, spermatocytes, and round spermatids, we identified a globally conserved m⁶A pattern between porcine and murine genes with spermatogenic function. We found that m⁶A was enriched in a group of genes that specifically encode the metabolic enzymes and regulators. In addition, transcriptomes in porcine male germ cells could be subjected to the m⁶A modification. Our data show that m⁶A plays the regulatory roles during spermatogenesis in pigs, which is similar to that in mice. Illustrations of this point are three genes (SETDB1, FOXO1, and FOXO3) that are crucial to the determination of the fate of SSCs. To the best of our knowledge, this study for the first time uncovers the expression profile and role of m⁶A during spermatogenesis in large animals and provides insights into the intricate transcriptional regulation underlying the lifelong male fertility in non-rodent mammalian species.
Animals ; Male ; Mice ; Cell Differentiation/genetics* ; Mammals/metabolism* ; Methylation ; RNA, Messenger/metabolism* ; Spermatogenesis/genetics* ; Spermatozoa/metabolism* ; Swine/genetics* ; Testis/metabolism* ; Transcriptome ; RNA Methylation/genetics*

Stress granules (SGs) are cytoplasmic ribonucleoprotein assemblies formed under stress conditions and are related to various biological processes and human diseases. Previous studies have reported the regulatory role of some proteins and linear RNAs in SG assembly. However, the relationship between circular RNAs (circRNAs) and SGs has not been discovered. Here, we screened both linear RNAs and circRNAs in SGs using improved total RNA sequencing of purified SG cores in mammalian cells and identified circular transcripts specifically localized in SGs. circRNAs with higher SG-related RNA-binding protein (RBP) binding abilities are more likely to be enriched in SGs. Furthermore, some SG-enriched circRNAs are differentially expressed in hepatocellular carcinoma (HCC) and adjacent tissues. These results suggest the regulatory role of circRNAs in SG formation and provide insights into the biological function of circRNAs and SGs in HCC.
Animals ; Humans ; RNA, Circular/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Stress Granules ; Cytoplasmic Granules/metabolism* ; Liver Neoplasms/metabolism* ; RNA/metabolism* ; Stress, Physiological/genetics* ; Mammals/genetics*

N⁶-methyladenine (m⁶A) is the most abundant RNA modification in mammalian messenger RNAs (mRNAs), which participates in and regulates many important biological activities, such as tissue development and stem cell differentiation. Due to an improved understanding of m⁶A, researchers have discovered that the biological function of m⁶A can be linked to many stages of mRNA metabolism and that m⁶A can regulate a variety of complex biological processes. In addition to its location on mammalian mRNAs, m⁶A has been identified on viral transcripts. m⁶A also plays important roles in the life cycle of many viruses and in viral replication in host cells. In this review, we briefly introduce the detection methods of m⁶A, the m⁶A-related proteins, and the functions of m⁶A. We also summarize the effects of m⁶A-related proteins on viral replication and infection. We hope that this review provides researchers with some insights for elucidating the complex mechanisms of the epitranscriptome related to viruses, and provides information for further study of the mechanisms of other modified nucleobases acting on processes such as viral replication. We also anticipate that this review can stimulate collaborative research from different fields, such as chemistry, biology, and medicine, and promote the development of antiviral drugs and vaccines.
Animals ; Viruses/genetics* ; RNA, Messenger/metabolism* ; Adenosine/metabolism* ; Cell Differentiation ; Mammals/metabolism*

Although the function of tRNAs in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice. Remarkable variation in the expression of tRNA isodecoders was observed among different tissues. When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons, we observed an expected reduction in the variation of anticodon expression across all samples, an unexpected smaller variation of anticodon usage bias, and an unexpected larger variation of tRNA isotype expression at amino acid level. Regardless of whether or not they share the same anticodons, the isodecoders encoding the same amino acids are co-expressed across different tissues. Based on the expression of tRNAs and the TE of mRNAs, we find that the tRNA adaptation index (tAI) and TE are significantly correlated in the same tissues but not between tissues; and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues. We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms. This study provides a resource for tRNA and translation studies, as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.
Animals ; Mice ; Anticodon/genetics* ; Transcriptome ; Protein Biosynthesis ; RNA, Transfer/chemistry* ; Amino Acids/metabolism* ; Mammals/metabolism*

Sleep is a highly conserved phenomenon in endotherms, and has a universal physiological function across all species. In mammals, sleep can be divided into two stages: rapid eye movement (REM) sleep and non-REM (NREM) sleep, which alternate in a cyclic manner. Humans spend about one-third of their lives asleep. Sufficient sleep is necessary for humans to sustain everyday functioning. Sleep plays an important role in regulating energy metabolism, immune defense, endocrine function, and the consolidation of memory process. With the development of social economy and the change of life style, sleep duration of the residents has gradually decreased and the incidence of sleep disturbances has increased. Sleep disturbances can lead to severe mental disorders, such as depression, anxiety disorders, dementia, and other mental diseases, and may increase the risk of physical diseases, such as chronic inflammation, heart disease, diabetes, hypertension, atherosclerosis and others. Maintaining good sleep is of great significance for developing social productive forces, promoting sustainable development of economic society, and is a necessary condition for carrying out the "Healthy China Strategy". The sleep research in China started in 1950s. After decades of development, researchers have made great progress in the molecular mechanisms of sleep and wakefulness, the pathogenesis of sleep disorders and the development of new therapies. With the advancement of science and technology and the public's attention to sleep, the level of clinical diagnosis and therapy of sleep disorders in China is gradually brought in line with international standards. The publication of diagnosis and treatment guidelines in the field of sleep medicine will promote the standardization of the construction. In the future, it is still necessary to promote the development of sleep medicine in the following aspects: Strengthening the professional training and discipline construction, improving the cooperation of sleep research, promoting the intelligent diagnosis and treatment of sleep disorders, and developing the new intervention strategies. Therefore, this review will comprehensively summarize the origin, current situation, and future expectations of sleep medicine in China, including discipline construction of sleep medicine, the number of sleep project grants, research findings, the status and progress of diagnosis and treatment of sleep disorders, and the development direction of sleep medicine.
Animals ; Humans ; Sleep ; Sleep Wake Disorders/therapy* ; Atherosclerosis ; China/epidemiology* ; Health Status ; Mammals

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 μg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated β-galactosidase stain kit(SA-β-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 μg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 μg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-β-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.
Humans ; Animals ; Periplaneta ; Sirtuin 1/genetics* ; K562 Cells ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Mammals