ABSTRACT
Motoric cognitive risk syndrome (MCR), as a new type of "pre-dementia" , is a sensitive prediction indicators of falls.There may be multiple attribution pathways between MCR and falls, which provides a new health management strategy in the fall prevention for community-dwelling elderly.The paper reviews the current status of MCR-related falling, attribution characteristics, the methods of risk assessment and health management strategies for older adults with MCR, with the aim of providing a reference for promoting systematic research on falls among senior citizens with MCR and the practice of falls prevention in the community.
ABSTRACT
Phylogenetically distant coronaviruses have evolved to use ACE2 as their common receptors, including NL63 and many Severe acute respiratory syndrome (SARS) coronavirus-related viruses. We recently reported two Middle East respiratory syndrome coronavirus (MERS-CoV) closely related bat merbecoviruses, NeoCoV and PDF-2180, use Angiotensin-converting enzyme 2 (ACE2) for entry. However, their host range and cross-species transmissibility remain unknown. Here, we characterized their species-specific receptor preference by testing ACE2 orthologs from 49 bats and 53 non-bat mammals. Both viruses exhibited broad receptor recognition spectra and are unable to use ACE2 orthologs from 24 species, mainly Yinpterochiropteran bats. Comparative analyses of bat ACE2 orthologs underscored four crucial host range determinants, all confirmed by subsequent functional assays in human and bat cells. Among them, residue 305, participating in a critical interaction, plays a crucial role in host tropism determination. NeoCoV-T510F, a mutation that enhances human ACE2 recognition, further expanded the potential host range via tighter interaction with an evolutionary conserved hydrophobic pocket. Our results elucidated the molecular basis for the species-specific ACE2 usage of MERS-related viruses across mammals and shed light on their zoonotic risks.
ABSTRACT
Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors1-4. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic5. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using "MERS-CoV-2" with both high fatality and transmission rate.
ABSTRACT
Objective To observe the effect of Allicin on renal tissue fibrosis in chronic renal failure (CRF) and to study the protective mechanism of Allicin on CRF rats. Methods The CRF rat models were established by intragastric administration of adenine solution (250 mg/kg) for 21 days. After successful modeling, 80 model rats were randomly divided into the normal control group, the model group and the allicin low, medium and high dose groups using a random number table method (n=20). Allicin low-, medium-, and high-dose groups were intragastrically administered with 2.5, 5, and 10 mg/ml of allicin respectively. The model group and normal control group were given an equal volume of normal saline, and were administered at 2 ml/kg body weight of the rats, with once a day continuous administration for 28 d. Two hours after the last dose, the kidney mass was measured and the kidney index was calculated. The pathological changes of renal tissue was observed by HE staining; the serum BUN, SCr, uric acid, and 24-hour urinary protein levels were measured by a biochemical analyzer; the levels of CRP, IL-6 and TNF-α in serum and the levels of ollagen type Ⅳ(CⅣ), type Ⅲ procollagen (PCⅢ), laminin (LN), Fibronectin (FN) in plasma were by ELISA; the expression of collagen type Ⅰ (Col Ⅰ), plasminogen activator inhibitor-1 (PAI-1) and MMP-1 were observed by mmunohistochemical staining. Results Compared with model group, the bodyweight of rats in allicin medium, high dose groups were increased and kidney index decreased (P＜0.05 or P＜0.01), kidney histopathology scores decreased (P＜0.01). Compared with model group, the level of BUN (14.51 ± 2.76 mmol/L, 11.48 ± 2.43 mmol/L vs. 24.07 ± 3.82 mmol/L), SCr (116.28 ± 27.35 μmol/L, 106.57 ± 24.18 μmol/L vs. 134.89 ± 35.02 μmol/L), Uric acid (83.34 ± 16.42 mmol/L, 77.86 ± 13.97 mmol/L vs. 114.76 ± 16.53 mmol/L), 24 h urinary protein (152.79 ± 48.43 mg, 137.03 ± 42.61 mg vs. 177.94 ± 96.47 mg), CRP (8.79 ± 1.84 mg/L, 7.51 ± 1.69 mg/L vs. 11.64 ± 1.95 mg/L), TNF-α (184.37 ± 24.15 ng/L, 126.82 ± 12.96 ng/L vs. 255.87 ± 31.93 ng/L) in the allicin medium and high dose groups were significantly decreased (P＜0.05 or P＜0.01); the levels of C-Ⅳ (40.26 ± 7.12 ng/ml, 23.79 ± 4.25 ng/ml vs. 67.53 ± 8.39 ng/ml), PC-Ⅲ (32.03 ± 5.89 ng/ml, 24.31 ± 5.84 ng/ml vs. 54.20 ± 7.08 ng/ml), LN (99.05 ± 38.17 ng/ml, 83.42 ± 28.83 ng/ml vs. 117.83 ± 35.76 ng/ml) in plasma in the allicin medium and high dose groups were significantly decreased and the level of FN (98.58 ± 21.43 mg/L, 125.96 ± 25.12 mg/L vs. 66.72 ± 13.09 mg/L) in plasma in the allicin medium and high dose groups were significantly increased (P＜0.05 or P＜0.01); the expression of Col Ⅰ (0.17 ± 0.03, 0.09 ± 0.03 vs. 0.27 ± 0.05), PAI-1 (0.20 ± 0.05, 0.16 ± 0.04 vs. 0.31 ± 0.08) were down-regulated and the expression of MMP-1 (0.10 ± 0.03, 0.22 ± 0.05 vs. 0.04 ± 0.02) were up-regulated (P＜0.05 or P＜0.01). Conclusion Allicin has protective effects on CRF rats by inhibiting the renal tissue fibrosis and alleviating inflammation.
ABSTRACT
Objective To compare the risk factors of breast cancer in Ningxia Hui and Han women,and to provide evidence for the prevention and control of breast cancer.Methods The female patients of breast cancer treated at the Affiliated Hospital of Ningxia Medical University between May 2013 and July 2014 were chosen for case study,while other patients treated at the same hospital and during the same period who did not have breast cancer were selected as a control. An epidemiological survey was conducted using the same questionnaire among the two groups.The survey involved general demographic information,menstrual history,reproductive history,life habit and family history of cancer.Risk factors of breast cancer in Hui and Han nationalities were analyzed by logistic regression analysis.Results Logistic regression analysis showed that the abortion number(OR =2.631,P =0.028)was a risk factor for the occurrence of breast cancer in women of the Hui nationality,while physical exercise (OR =0.177,P =0.040)was a protective factor.Tumor suffered by immediate family members (OR =4.249,P =0.014),abortion number (OR =1.602,P =0.001 ),the age of the first childbirth (OR =1.253,P =0.001 )and the age of first marriage(OR =1.223,P =0.001 )were the major risk factors while physical exercise (OR =0.422,P =0.001 )was a protective factor against breast cancer in Han nationality. Conclusion The risk factors of breast cancer in the women of Hui and Han nationalities are consistent in terms of the total number of abortions and physical exercise.Compared with the Hui people,the age of first marriage,the age of first child birth,and tumor suffered by immediate family members also play a role in the occurrence of breast cancer in the Han na-tionality.
