Lactylation (Kla), a protein post-translational modification characterized by the covalent conjugation of lactyl groups to lysine residues in proteins, is widely present in living organisms. Since its discovery in 2019, it has attracted much attention for its role in regulating major pathological processes such as tumorigenesis, neurodegenerative diseases, and cardiovascular diseases. By mediating core biological processes such as signal transduction, epigenetic regulation, and metabolic homeostasis, lactylation contributes to disease progression. However, the lactylation donor lactyl-CoA has a low intracellular concentration, and the specific enzyme catalyzing lactylation is not yet clear, which has become an urgent issue in lactate research. A groundbreaking study in 2024 found that alanyl-transfer t-RNA synthetase 1/2 (AARS1/2), members of the aminoacyl-tRNA synthetase (aaRS) family, can act as protein lysine lactate transferases, modifying histones and metabolic enzymes directly with lactate as a substrate, without relying on the classical substrate lactyl-CoA, promoting a new stage in lactate research. Although exercise significantly increases lactate levels in the body and can induce changes in lactylation in multiple tissues and cells, the regulation of lactylation by exercise is not entirely consistent with lactate levels. Research has found that high-intensity exercise can induce upregulation of lactate at 37 lysine sites in 25 proteins of adipose tissue, while leading to downregulation of lactate at 27 lysine sites in 22 proteins. The level of lactate is not the only factor regulating lactylation through exercise. We speculate that the lactate transferase AARS1/2 play an important role in the process of lactylation regulated by exercise, and AARS1/2 should also be regulated by exercise. This review introduces the molecular biology characteristics, subcellular localization, and multifaceted biological functions of AARS, including its canonical roles in alanylation and editing, as well as its newly identified lactate transferase activity. We detail the discovery of AARS1/2 as lactylation catalysts and the specific process of them as lactate transferases catalyzing protein lactylation. Furthermore, we discuss the pathophysiological significance of AARS in tumorigenesis, immune dysregulation, and neuropathy, with a focus on exploring the expression regulation and possible mechanisms of AARS through exercise. The expression of AARS in skeletal muscle regulated by exercise is related to exercise time and muscle fiber type; the skeletal muscle AARS2 upregulated by long-term and high-intensity exercise catalyzes the lactylation of key metabolic enzymes such as pyruvate dehydrogenase E1 alpha subunit (PDHA1) and carnitine palmitoyltransferase 2 (CPT2), reducing exercise capacity and providing exercise protection; physiological hypoxia caused by exercise significantly reduces the ubiquitination degradation of AARS2 by inhibiting its hydroxylation, thereby maintaining high levels of AARS2 protein and exerting lactate transferase function; exercise induced lactate production can promote the translocation of AARS1 cytoplasm to the nucleus, exert lactate transferase function upon nuclear entry, regulate histone lactylation, and participate in gene expression regulation; exercise induced lactate production promotes direct interactions between AARS and star molecules such as p53 and cGAS, and is widely involved in the occurrence and development of tumors and immune diseases. Elucidating the regulatory mechanism of exercise on AARS can provide new ideas for improving metabolic diseases and promote health through exercise.

Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

ObjectiveTo observe the effect of Yangxin Tongmai Formula （养心通脉方） by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease （PCHD） with blood stasis syndrome， and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group， model group and Yangxin Tongmai Formula group， and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling， rats in Yangxin Tongmai Formula group were gavaged with 18 g/（kg‧d） of Yangxin Tongmai Formula， and rats in blank group and the model group were gavaged with 4 ml/（kg‧d） of 0.9% NaCl solution， and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition， rats with successful modelling of PCHD with blood stasis were randomly divided into model group， Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice in the heart channel period （12：00） and pericardium channel period （20：00）］， the Yangxin Tongmai Formula control group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice at 8：00 and 18：00］ and the Atorvastatin Calcium group ［atorvastatin calcium tablets solution 1.8 mg/（kg‧d） at the same intervention time as that in Yangxin Tongmai Formula control group］， and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/（kg‧d） for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage， the blood lipids ［including total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）］ levels of rats in each group were detected； the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes； the levels of serum inflammation indexes ［tumour necrosis factor alpha （TNF-alpha）， lipopolysaccharide （LPS）， and interleukin 10 （IL-10）］ were detected； immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 （Calm2）， calcium voltage-gated channel subunit α1s （Cacna1s）， and phospholipase Cβ1 （Plcb1）. Compared with the blank group， rats in the model group showed elevated levels of TC， LDL， TNF-α and LPS， and decreased levels of HDL and IL-10 （P＜0.05 or P＜0.01）； HE staining showed obvious swelling of myocardial fibres， accompanied by a large number of inflammatory cell infiltration， and thickening of the inner wall of the aortic vessels with internal wall damage， which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group， the TC， LDL， TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group， the Yangxin Tongmai Formula control group， and the atorvastatin calcium group all reduced， and the contents of HDL and IL-10 all elevated （P＜0.05）， with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration， and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group， LDL， TNF-α and LPS contents reduced， and IL-10 contents increased in the midnight-noon ebb-flow administration method group （P＜0.05）. Compared with the model group， the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group （P＜0.05）； compared with the Yangxin Tongmai Formula control group， the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group （P＜0.05）. ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period （12：00） and pericardium channel period （20：00） was more effective in improving the blood lipid level， inhibiting inflammation， and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome， and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To explore the task-state electroencephalogram(EEG)characteristics of working memory in patients with post-stroke aphasia(PSA). Methods From September,2020 to February,2021,a total of eight patients with PSA(PSA group)and eight healthy adults(HC group)were recruited to collect EEG and memory scale data.The EEG data of working memory task-states were used to analyze the characteristics of the EEG frequency band indicators in time domain event-related potentials(ERP)and frequency;and the correlation with the items in the memory scale. Results Finally,five patients and five controls were included.N1 and P2 components were induced in the frontal area,and P300 components were induced in the parieto-occipital area.Compared with HC group,the activation of N1 and P2 increased in central prefrontal region,while the activity of P300 decreased in the right parieto-occipital re-gion in PSA group(|t|>2.193,P<0.05).The energy of theta band decreased in the right prefrontal region and the central parieto-occipital region,the energy of alpha1 band decreased in the left parieto-occipital region,and the energy of gamma band increased in the left central region(t>2.398,P<0.05).The energy of gamma band correlated with immediate recall(r = 0.914,P = 0.030)and correct recognition(r = 0.931,P = 0.022)of Auditory Verbal Learning Test,and inverting(r = 0.924,P = 0.025)and anterograde(r = 0.889,P = 0.044)of Digit Span Test. Conclusion Visual working memory task can activate the compensatory processing activity of memory related brain re-gions after PSA,which can be used as an objective indication for the evaluation of PSA working memory related research.There is close relationship between language impairment and working memory.

Objective: To explore the association between lifestyle and fat mass index (FMI) in different positions of children and adolescents aged 7-18, so as to provide a scientific basis for health promotion in children and adolescents. Methods: A total of 1 531 students aged 7-18 was selected by intentional sampling from 4 schools in Tongzhou District, Beijing from September to December in 2020 and August in 2022. Questionnaire survey was used to collect lifestyle including dietary behavior, moderate to vigorous physical activity, smoke and drink behaviors, sleep time and sleep quality. Dual energy Xray absorptiometry was employed to assess fat mass, and calculated total, android, trunk, hip, gynoid and leg fat mass index (FMI). The ttest and Chisquare test were used to compare the differences of different lifestyle. Logistic regression was used to analysis association between lifestyle and body composition in different positions. Results: Compared with healthy lifestyle, unhealthy lifestyle had higher risk for hightrunk FMI (OR=1.40, P<0.05). After adjusted for sex and age, unhealthy lifestyle had higher risk for hightotal FMI, highandroid FMI, hightrunk FMI (OR=1.37, 1.37, 1.50, P<0.05), compared with healthy lifestyle. Stratified analysis found the associations between unhealthy lifestyle and hightotal FMI, highandroid FMI, hightrunk FMI, and highthigh FMI were only significant in girls with 7-12 years old (OR=2.13, 2.46, 2.13, 2.13, P<0.05). Conclusions Unhealthy lifestyle is associated with hightotal FMI, highandroid FMI and hightrunk FMI. A healthy lifestyle should be maintained during puberty, especially before puberty, to help children and adolescents reduce body fat and promote a balanced distribution of body composition.

Cationic liposomes,as non-viral vectors,are widely used in gene therapy and gene silencing.Although numerous cationic liposomes have various structures,they can all improve the per-formance of gene delivery.As gene therapy is increasingly studied,it may be foreseen that new cationic lipoplexes will be explored.In this review,we aim to discuss four constituent domains of cationic lipids(headgroup,hydrophobic domain,linker and helper lipids)in gene delivery.This article attempts to demonstrate that various lipid structures show different transfection efficiency and cytotoxicity by sum-marizing the similarities and differences between the four parts of cationic lipids.Furthermore,their major influencing factors are covered.Finally,three clinical cases of ionizable lipids are described to reveal their characteristics and differences from cationic lipids.This paper is intended to provide a conceptual framework for the design of cationic liposomes and for the selection of cationic lipids.

Objective:To compare the effects of high-power and conventional power atrial fibrillation ablation on intraoperative acute pulmonary vein isolation, postoperative troponin levels, and atrial fibrillation recurrence.Methods:A retrospective selection was conducted on 105 patients with paroxysmal atrial fibrillation admitted to the Baoding NO.1 Central Hospital from January 2017 to December 2020. According to different treatment methods, they were divided into a high-power ablation group of 52 cases and a conventional power ablation group of 53 cases. The intraoperative rate of single circle acute pulmonary vein isolation, the recovery of electrical conduction after acute pulmonary vein isolation, and the location and number of points that need to be added were compared between the two groups; At the same time, two groups were compared in terms of surgical time, ablation time, surgical radiation exposure time and radiation dose, intraoperative complications postoperative cardiac troponin levels at 12 hours, and recurrence of atrial fibrillation within 1 year after ablation.Results:The intraoperative single loop pulmonary vein isolation rate and postoperative troponin levels in the high-power atrial fibrillation ablation group were higher than those in the conventional atrial fibrillation ablation group (all P<0.05). The surgical time, ablation time, and the number of sites and points that need to be added during surgery were less than those in the conventional atrial fibrillation ablation group (all P<0.05). There was no statistically significant difference in the incidence of intraoperative complications and postoperative atrial fibrillation recurrence between the two groups (all P>0.05). Conclusions:High power atrial fibrillation ablation has a higher single loop acute pulmonary vein isolation rate, fewer patch sites and points, shorter surgical time, and greater ablation damage compared to conventional ablation, and the clinical efficacy of the two groups is similar after surgery.