Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

Objective: To observe the efficacy of unblocking and regulating the Belt Vessel acupuncture method for patients with abdominal obesity in Germany and its influence on the body fat parameters and glycolipids metabolism. Methods: A total of 82 cases of abdominal obesity in Germany were selected. There were two dropout cases in the treatment process. All of the patients received acupuncture at Daimai (GB26), Daheng (SP15), Tianshu (ST25), Zhongwan (CV12), Shuidao (ST28), Waiguan (TE5), and Zulinqi (GB41). The patients received acupuncture therapy once every 2-3 d, 3 times a week. The treatment duration lasted 4 weeks. Before and after treatment, the body mass (BM), waist circumference (WC), abdominal circumference (AC), hip circumference (HC), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (GLU) were measured respectively, and the body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body fat rate (BFR) were calculated. Results: After treatment, the total effective rate was 72.5％; the levels of BM, WC, AC, HC, BMI, WHR, WHtR, BFR, TC, LDL-C, and GLU declined significantly compared with those before treatment (P<0.01), while the TG and HDL-C slightly declined, but the differences were statistically insignificant (P>0.05). Conclusion: The unblocking and regulating the Belt Vessel acupuncture method can significantly reduce body fat parameters such as BM, AC, and BFR, and correct the disorders of glucose and lipid metabolism in patients with abdominal obesity in Germany.

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Humans ; NF-kappa B/metabolism* ; Lipopolysaccharides/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Acute Lung Injury/metabolism* ; Lung ; Phosphate-Binding Proteins/therapeutic use* ; Pore Forming Cytotoxic Proteins/therapeutic use*

Objective:To investigate the correlation between cognitive function and living ability of older adult patients living in a mining community.Methods:A total of 180 older adult patients living in a mining community who received treatment during July-October 2019 were included in this study. They were randomly divided into the low-age group (< 68 years old, n = 94) and the high-age group (≥ 68 years old, n = 86). Cognitive function and living ability were evaluated using the Mini-Mental State Examination (MMSE), The Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL). The relationship between cognitive function and living ability was investigated using hierarchical analysis and Pearson correlation analysis. Results:The proportions of older adult patients with abnormal cognitive function identified by the MMSE and MoCA were 39.4% and 66.0%, respectively in the low-age group, and they were 32.6% and 61.6%, respectively in the high-age group. The MoCA had a greater performance in identifying abnormal cognitive function in each group than the MMSE ( χ2 = 26.69, 10.18, both P < 0.001). There were no significant differences in proportions of older adult patients with abnormal cognitive function identified by the MMSE and MoCA between low-age and high-age groups ( χ2 = 0.90, 0.36, both P > 0.05). The proportion of older adult patients with abnormal living ability was not significantly different between low-age and high-age groups (4.3% vs. 10.5%, χ2 = 2.58, P > 0.05). Compared with patients negative for MMSE items, living ability and instrumental activity of daily living increased by 7.0% and 9.4% in low-age patients positive for MMSE items (both P < 0.05). Compared with patients negative for MoCA items, living ability increased by 3.5% in low-age patients positive for MoCA items ( P < 0.05). Correlation analysis revealed that total scores of MMSE and MoCA were significantly negatively correlated with ADL score ( r = -0.26, -0.27, both P < 0.001) and instrumental activity of daily living score ( r = -0.27, -0.27, P < 0.001). Conclusion:Cognitive function and living ability are correlated in older adult patients living in a mining community. We should pay attention to the screening results of cognitive disorder in older adult patients and improve their living ability by improving their cognitive function.

ObjectiveTo investigate the immediate effect of wearing a soft ankle brace on dynamic and static balance function and biomechanics of affected lower limbs during walking in chronic ankle instability (CAI) patients. MethodsFrom January to August, 2021, 40 CAI patients from Musculoskeletal Rehabilitation Center, Beijing Rehabilitation Hospital, Capital Medical University were measured dynamic and static balance indexes with Zebris FDM-System and Y balance test, before and after wearing a soft ankle brace; while the kinetics indexes and surface electromyography of the affected lower extremities during walking were collected with Zebris FDM-System and a surface electromyography telemeter simultaneously. ResultsThe velocity and area of center of pressure reduced in both open and closed eye modes (|t| > 2.876, P < 0.01), the Y-balance scores increased in all the directions (|t| > 21.212, P < 0.001) after wearing brace; while the peak pressures and impulses increased in the midfoot and medial forefoot regions (|t| > 2.057, P < 0.05), and decreased in the lateral heel, lateral forefoot and toe regions (|t| > 2.464, P < 0.05), and the root mean square of surface electromyography increased in the tibialis anterior and lateral gastrocnemius (|t| > 2.159, P < 0.05) during walking. ConclusionWearing soft brace can immediately improve dynamic and static balance of CAI patients, and optimize plantar kinetic distribution and enhance activation of the anterior tibial and the lateral head of gastrocnemius of the affected limb during walking, to improve motor control of CAI patients.

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective:To observe the clinical features of retinopathy of prematurity (ROP) in multiple fetuses.Methods:Retrospective clinical study. From December 2009 to June 2018, 758 premature or low-weight multiple fetuses (multiple fetuses group) and 2363 simultaneous single fetuses (single fetuses group) who were admitted to the Department of Ophthalmology and Neonatal Department of Dongguan People’s Hospital and underwent ROP screening were included in the study. Among the multiple pregnancy group, there were 735 twins and 23 triplets; 441 males and 317 females. The mean gestational age was 32.22±2.14 weeks, and the mean body weight was 1.69±0.43 kg. There were 202 of natural births and 556 of cesarean sections. A total of 750 cases have a history of oxygen. Among the singleton group, 1421 were males and 942 were females. The mean gestational age was 32.06±2.52 weeks, and the mean body weight was 1.70±0.46 kg. There were 1146 of natural births and 1217 of cesarean sections. A total of 2333 cases have a history of oxygen. The detection rate of multiple ROP, gestational age, birth weight, sex composition ratio, mode of birth, time of first ROP diagnosis, and severity of ROP were observed. χ2 test was used to compare the rate between groups, and t test was used to compare the mean between groups. Results:Among the multiple pregnancy group, there were 68 cases (8.97%) of ROP. Among them, 64 twins (8.71%, 64/735), 4 triplets (17.39%, 4/23). Among the singleton group, there were 187 cases (7.91%) of ROP. With the increase of fetal number, the detection rate of ROP increased, but there was no significant difference ( χ2=3.097, P=0.213). There was no significant difference in the detection rate of ROP between multiple fetuses and single fetuses ( χ2=0.855, P=0.355). There was no significant difference in sex ratio ( χ2=0.069), mode of production ( χ2=1.900), birth weight ( t=0.139), gestational age ( t=-0.478), and time of first ROP diagnosis ( t=0.371) between ROP cases of multiple fetuses and single fetuses ( P=0.793, 0.168, 0.889, 0.633, 0.371). There was no significant difference in the constituent ratio of severity of ROP lesions between multiple fetuses and single fetuses ( χ2=3.003, P=0.223). Conclusion:There is no significant difference in ROP incidence, gestational age, birth weight, diagnosis time and severity of ROP between multiple fetuses and single fetuses under the same conditions.