One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:To analyze clinical characteristics of Mycoplasma pneumoniae-induced rash and mucositis in children. Methods:Clinical data were collected from children diagnosed with Mycoplasma pneumoniae -induced rash and mucositis in the Department of Dermatology, Capital Center for Children's Health, Captital Medical University from August 1, 2023, to December 1, 2023, and their clinical features were analyzed. Results:A total of 15 children with Mycoplasma pneumoniae-induced rash and mucositis were collected, including 8 males and 7 females, aged 4 to 12 years. They were clinically characterized by obvious mucositis, and skin lesions were relatively mild. Oral mucosal involvement was observed in 13 cases, including lip ulcers (12 cases), oral mucositis (7 cases), tongue ulcers (3 cases), and glossitis (1 case) ; ocular mucosal involvement was reported in 7 cases, including suppurative conjunctivitis (4 cases), and eyelid edema (3 cases) ; 3 children had vulvogenital mucosal involvement, including coronary sulcus ulcers (1 case), urethral meatus ulcers (1 case), labia minora ulcers (1 case), and perianal ulcers (1 case) ; 1 child had nasal mucosal ulcers. Skin lesions occurred on the upper limbs in 5 cases, on the lower limbs in 6 cases, on the face in 2 cases, on the vulva in 2 cases, as well as on the trunk in 1 case. The types of skin lesions included targetoid erythema in 11 cases, vesiculobullous lesions in 6 cases and atypical targetoid erythema in 2 cases. PCR for the detection of Mycoplasma pneumoniae in vesiculobullous fluids showed negative results in the 6 patients with vesiculobullous lesions. The patients received systemic and topical treatment with antibiotic agents and glucocorticoids, as well as supportive therapy. Main pulmonary symptoms as well as skin and mucosal lesions of the 15 children subsided within 3 weeks, and they all had a favorable prognosis, without obvious complications or sequelae. Conclusion:Mycoplasma pneumoniae-related skin and mucosal lesions predominantly present as mucositis, with mild or absent skin involvement. The disorder usually has a mild course, characterized by short disease duration and favorable prognosis.

AIM: To investigate the correlation of degree of myopia in adolescents with axial length, corneal curvature and axial ratio.METHODS: Cross-sectional study. A total of 246 adolescents(492 eyes)aged 8-18 years consecutively enrolled for orthokeratology lens fitting at the Fifth Affiliated Hospital of Zhengzhou University between 2021 and 2023 were included based on random sampling method, with 447 eyes finally included due to the elimination of 45 eyes that did not meet the inclusion criteria. Biometric measurements under scotopic conditions assessed axial length(AL), corneal radius of curvature(CR), and AL/CR ratio. Cycloplegic refraction determined spherical equivalent(SE), classifying eyes into mild(216 eyes)or moderate(231 eyes)myopia groups. Furthermore, the correlation of degree of myopia with AL, CR and AL/CR was analyzed by multiple linear regression analysis.RESULTS: A statistically significant difference in myopia severity was observed between the 8-12-year-old and 13-18-year-old age groups(all P<0.001). There were statistically significant differences between mild and moderate groups in SE, AL and AL/CR(all P<0.001). Linear regression analysis revealed significant negative correlations of SE with AL and AL/CR(r=-0.531, -0.598, all P<0.001). The areas under the ROC curve(AUC)for predicting moderate myopia were 0.812(95% CI: 0.773-0.852)for AL/CR combined with gender and age, 0.800(95% CI: 0.759-0.841)for AL/CR alone, 0.726(95% CI: 0.680-0.773)for AL alone, and 0.548(95% CI: 0.494-0.601)for CR alone. The optimal AL/CR cut-off value for predicting moderate myopia was 3.189(sensitivity: 0.632, specificity: 0.852), suggesting its potential as a clinical threshold.CONCLUSION: In adolescents with mild-to-moderate myopia, AL/CR, AL, and SE showed significant negative correlations. The combination of AL/CR with gender and age demonstrated the highest diagnostic accuracy for SE. AL/CR shows independent predictive value for myopia degree in adolescents, irrespective of refractive status.

Objective:To analyze clinical characteristics of Mycoplasma pneumoniae-induced rash and mucositis in children. Methods:Clinical data were collected from children diagnosed with Mycoplasma pneumoniae -induced rash and mucositis in the Department of Dermatology, Capital Center for Children's Health, Captital Medical University from August 1, 2023, to December 1, 2023, and their clinical features were analyzed. Results:A total of 15 children with Mycoplasma pneumoniae-induced rash and mucositis were collected, including 8 males and 7 females, aged 4 to 12 years. They were clinically characterized by obvious mucositis, and skin lesions were relatively mild. Oral mucosal involvement was observed in 13 cases, including lip ulcers (12 cases), oral mucositis (7 cases), tongue ulcers (3 cases), and glossitis (1 case) ; ocular mucosal involvement was reported in 7 cases, including suppurative conjunctivitis (4 cases), and eyelid edema (3 cases) ; 3 children had vulvogenital mucosal involvement, including coronary sulcus ulcers (1 case), urethral meatus ulcers (1 case), labia minora ulcers (1 case), and perianal ulcers (1 case) ; 1 child had nasal mucosal ulcers. Skin lesions occurred on the upper limbs in 5 cases, on the lower limbs in 6 cases, on the face in 2 cases, on the vulva in 2 cases, as well as on the trunk in 1 case. The types of skin lesions included targetoid erythema in 11 cases, vesiculobullous lesions in 6 cases and atypical targetoid erythema in 2 cases. PCR for the detection of Mycoplasma pneumoniae in vesiculobullous fluids showed negative results in the 6 patients with vesiculobullous lesions. The patients received systemic and topical treatment with antibiotic agents and glucocorticoids, as well as supportive therapy. Main pulmonary symptoms as well as skin and mucosal lesions of the 15 children subsided within 3 weeks, and they all had a favorable prognosis, without obvious complications or sequelae. Conclusion:Mycoplasma pneumoniae-related skin and mucosal lesions predominantly present as mucositis, with mild or absent skin involvement. The disorder usually has a mild course, characterized by short disease duration and favorable prognosis.

AIM: To study the degree of astigmatism, axial distribution and axial symmetry pattern of binocular astigmatism in primary and secondary school students aged 7-18 years with myopia.METHODS:A total of 239 cases(478 eyes)of primary and secondary school students aged 7-18 years who underwent keratoplasty for myopia correction at the Fifth Affiliated Hospital of Zhengzhou University from 2020 to 2022 were randomly selected, and optometry was performed under ciliary muscle paralysis and was statistically analyzed.RESULTS:Astigmatism degree: 0.25 to 1.00 D accounted for 78.5%, 1.25 to 2.00 D accounted for 17.1%, and >2.00 D accounted for 4.4%. The axial distribution of astigmatism: 86.6% was astigmatism with the rule, 5.9% was astigmatism against the rule, and 7.5% was oblique astigmatism; both genders and different astigmatism degrees were dominated by astigmatism with the rule, and there were differences with the other two axes(both P<0.05). Axial symmetry pattern of astigmatism: the median axial difference in astigmatism between the direct symmetry model and the mirror symmetry model was 7° and 10°, respectively, with no statistical significance in both models(P=0.158), and there was no difference between the two in gender, degree of astigmatism, and axial distribution of astigmatism, but in the age group of 7-12 years old, the difference between the axial astigmatism of the direct symmetry model and the mirror symmetry model was statistically significant(P=0.027).CONCLUSION:The axial distribution of binocular astigmatism in myopic primary and middle school students is mostly astigmatism with the rule; the degree of astigmatism is more common from 0.25 to 1.0 D; however, there is no tendency for axial symmetry pattern of astigmatism.

The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

Objective: This study was to investigate the effects of MEHP on isolated rat heart and explore its mechanism. Methods: The experiments were performed with Langendorff-perfused rat heart with a Langendorff apparatus. 35 SD rats were used in the experiment and there were 5 rats per group. MEHP at doses of 3.125, 6.250, 12.500 and 25.000 μmol/L were given to the hearts for 25 minutes. Effects of NAC at concentration of 5 mmol/L were evaluated by co-treatment with 12.500 or 25.000 μmol/L MEHP. Data was collected per 5 minutes for 25 minutes. The heart rate, LVDP, LVEDP, dp/dtmax, and dp/dtmin were measured and analyzed using a PL3508 Data Acquisition and Analysis System. 200 waves at least were required each time. LDH contents in heart lavage fluid were determined by photometric assays using the automated biochemical analyzer. A section of the heart tissue was used for histopathological examination. DCFH-DA method was used to detect the levels of reactive oxygen species in different groups of heart tissues. Results: There was a concentration dependent decrease of heart rate (P<0.05) . At concentrations of 6.250, 12.500 and 25.000 μmol/L, MEHP significantly decreased the LVDP, dp/dtmax and dp/dtmin (P<0.05) , and this decrease is more pronounced with perfusion time. As the MEHP was given up to 6.250, 12.500 and 25.000 μmol/L, a statistical significance was found in the increase of LVEDP (P<0.05) . For dp/dtmin, a significant increase was observed at the concentration of 3.125 μmol/L when perfused with 10 and 15 min (P<0.05) , but this increase disappeared over time. LDH in cardiac perfusate increased as the MEHP given a higher concentration (P<0.05) . Compared with the control group, Histopathological analysis showed edema of myocardial tissue and cells, and inflammatory cells infiltration and myocardial cells necrosis were obvious in the MEHP perfusion groups. Myocardial ROS levels of the four MEHP treatment groups were all significantly higher than that of control group (P<0.05) . These heart damage induced by MEHP could be attenuated by NAC in different degrees. Conclusion MEHP can induce damage to myocardial tissue of isolated rat heart and one possible mechanism is the oxidative stress

BACKGROUND:Stem cel transplantation is a new method for blinding eye disease. But there is a lack of research about the protective effect of retinal stem cel transplantation on retinal ganglion cel s in glaucoma. OBJECTIVE:To explore the protective effect of retinal stem cel transplantation on retinal ganglion cel s of rats with glaucoma. METHODS:Forty-five Sprague-Dawley rats were randomly divided into three groups (n=15 per group) including control, model and retinal stem cel transplantation groups. Rat models of glaucoma were prepared in the latter two groups, and at 7 days after modeling, rats in the three groups were given intravitreal injection of 1 mL retinal stem cel s (5x106 cel s), the same amount of PBS, and no treatment, respectively. Subsequently, relative indicators were detected at 2 weeks after transplantation. RESULTS AND CONCLUSION:The expressions of brain-derived neurotrophic factor and insulin-like growth factor I protein as wel as the number of retinal ganglion cel s were the highest in the control group, fol owed by the retinal stem cel transplantation group model group, and the lowest in the model group (P<0.05). The number of apoptotic retinal ganglion cel s in model group was significantly higher than that of control group (P<0.05), and which in the retinal stem cel transplantation group was significantly lower than that in the model group (P<0.05), but higher than that in the control group (P<0.05). These results suggest that retinal stem cel transplantation for rat glaucoma can exert a protective effect on retinal ganglion cel s.

BACKGROUND:Studies have found that a variety of biological materials can be used for preparing corneal stroma scaffolds that have good biocompatibility, but research on preparation and biocompatibility of the acel ular porcine corneal stroma scaffold is little. OBJECTIVE:To explore the preparation and biocompatibility of the acel ular porcine corneal stroma scaffold. METHODS:Acel ular porcine corneal stroma scaffold and its extract were prepared. Wel-grown human corneal stromal cel s were selected and cultured in the extract of acel ular porcine corneal stroma scaffold (experimental group) or in the complete medium (control group), respectively. After 1, 2 and 3 days of culture, the proliferation ability of human corneal stromal cel s was detected by MTT assay. In the meanwhile, human corneal cel s were directly seeded onto the acel ular porcine corneal stroma scaffold, and then the cel growth on the scaffold was detected using immunochemical method. RESULTS AND CONCLUSION:The number of human corneal stromal cel s was in a rise with time in the two groups, and absorbance values had no significant difference between two groups at different time points of culture. Human corneal stromal cel s grew wel on the scaffold, and were positive for cel integrinβ1, vimentin, aldehyde dehydrogenase 3A1, as wel as CD34, CDK2 and K-Ras. These results show that the acel ular porcine corneal stroma scaffold has no cytotoxicity, and has good biocompatibility.

Objective To observe the effects of treadmill training at different intensities on the expression of p-AKT in rats' gastrocnemius muscles after focal cerebral ischemia,and to investigate whether intensive training is beneficial for the recovery of motor function.Methods Left middle cerebral artery occlusion (MCAO) was induced in 120 male Wistar rats using the intraluminal thread method,and they were divided into an MCAO group (no training),a normal training group (treadmill training once a day for 30 min) and an intensive training group (treadmill training twice a day for 60 min),each of 30 rats.There was also a sham control group with 30 members not given MCAO or training.The four groups were further divided into 3 day,7 day and 14 day subgroups.Five rats randomly selected from each subgroup were sacrificed for hematoxylin-eosin staining after 4％ paraformaldehyde treatment.Neurological function was evaluated using Zausinger scores,and the expression of p-Akt was detected by western blotting.Results No significant differences in Zausinger scores were observed between the intensive training group and the normal training group after 1,3 or 7 days of training.However the average Zausinger score in the intensive training group was significantly higher than in the normal training group after 14 d of treadmill training.After 7 d and 14 d of treadmill training the average cross-sectional area of the gastrocnemius muscles in the sham group was significantly higher than in the other three groups.The average area of the intensive training group was significantly larger than that of the normal training group.The expression of p-Akt in the gastrocnemius was significantly increased in the intensive training group compared with the normal training group in the 7 day and 14 day subgroups.Conclusion Treadmill training can improve the expression of p-Akt in atrophied gastrocnemius muscles caused by MCAO.Intensive training is more effective for the recovery of muscle function.