ABSTRACT
ACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2s binding, how to efficiently and flexibly control ACE2 levels for prevention of SARS-CoV-2 infection has not been explored. Here, we revealed Vitamin C (VitC) administration as an effective strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in a dose-dependent manner, while partial reduction of ACE2 can greatly restrict SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination at Lys788 and degradation of ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC administration reduced host ACE2 and largely blocked SARS-CoV-2 infection in mice. This study identified an in vivo ACE2 balance controlled by both USP50 and an essential nutrient VitC, and revealed a critical role and application of VitC in daily protection from SARS-CoV-2 infection. HighlightsO_LIVitC reduces ACE2 protein levels in a dose-dependent manner C_LIO_LIVitC and USP50 regulate K48-linked ubiquitination at Lys788 of ACE2 C_LIO_LIVitC blocks the interaction between USP50 and ACE2 C_LIO_LIVitC administration lowers host ACE2 and prevents SARS-CoV-2 infection in vivo C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/499651v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@196682borg.highwire.dtl.DTLVardef@190f14dorg.highwire.dtl.DTLVardef@d22b59org.highwire.dtl.DTLVardef@1c0faa_HPS_FORMAT_FIGEXP M_FIG C_FIG The deubiquitinase USP50 controls ACE2 protein stability and levels, while Vitamin C blocks the USP50-ACE2 interaction and therefore results in ACE2 degradation, offering a flexible and efficient approach to protection of the host from SARS-CoV-2 infection.
ABSTRACT
Objective@#To analyze the causes of equinus deformity caused by intramuscular venous malformation onset posterior muscles of leg, and discuss the corresponding treatment methods.@*Methods@#A retrospective study was conducted on 69 cases of intramuscular venous malformations with equinus deformity from January 2012 to December 2017. Based on patient's main complain, physical examination and imaging data, the causes were divided into two categories: pain disorder and contracture disorder. Classification was on the basis of definite diagnosis of MRI. When the main complaint of medical history and physical examination indicated pain relief or passivity of the affected limb, and when the back extension of ankle joint was greater than 75 degrees, it was a pain disorder; when the medical history and physical examination indicated pain relief or passivity of the affected limb, the back extension of ankle joint was less than 15 degrees, it was a contracture disorder. Therapeutic methods included drug conservative treatment and surgical treatment. For the patients with pain disorder, the first choice was drug conservative treatment, and for the patients with contracture disorder, the first choice was surgery. Operative methods include simple venous malformation resection, venous malformation resection and Z-type Achilles tendon anastomosis lengthening. After operation patients received systematic functional rehabilitation exercise and calculated the satisfaction rate.@*Results@#13 cases of painful disorders were firstly treated by conservative medicine, but 4 cases were treated by operation after series of conservative treatments, satisfaction rate was 69.2%(9/13). 56 contracture cases were treated by operation, including 11 cases of simple venous malformation resection, 45 cases resection and Z-type anastomosis lengthening of Achilles tendon. All the patients were followed up for 6 months to 2 years after operation. 53 patients recovered to normal walking after operation, and 3 patients had mild limp, satisfaction rate was 94.6%(53/56). Patient satisfaction was 100%.@*Conclusions@#The equinus deformity caused by intramuscular venous malformation onset posterior muscles of leg affect the quality of life. Muscle/tendon contracture was the main cause. Correct surgical treatment combined with early rehabilitation exercise post operation can restore normal walking posture.
ABSTRACT
Objective To observe the alterations in brain gray matter volume(GMV)in idiopathic generalized epilepsy(IGE)patients with typical absence seizure. Methods Nine IGE patients with typical absence seizure and 16 healthy volunteers were prospectively recruited from People's Hospital of Zhengzhou University from September 2012 to January 2014. By using a 3. 0T magnetic resonance imaging(MRI)and voxel - based morphometry(VBM)method, their whole brain structures and their brain GMV were scanned and analyzed,respectively,then the changes in GMV were observed. Results Compared with healthy control group,brain GMV extensively decreased in IGE patients with typical absence seizure. Thirteen regions with significant differences were as follows:the right rectal gyrus(t = 3. 13,P ﹤0. 01),the left rectal gyrus(t = 4. 82,P ﹤ 0. 01),the right calcarine/ cuneus/ gyrus lingualis/ occipital gyrus/ inferior oc-cipital gyrus(t = 6. 86,P ﹤ 0. 01),right gyrus lingualis(t = 4. 01,P ﹤ 0. 01),the left gyrus lingualis/ inferior occipital gyrus(t = 3. 73,P ﹤ 0. 01),the left inferior occipital gyrus/ gyrus lingualis(t = 5. 42,P ﹤ 0. 01),the left middle occipi-tal gyrus(t = 3. 76,P ﹤ 0. 01),the right middle occipital gyrus/ superior occipital gyrus/ middle temporal gyrus( t =3. 85,P ﹤ 0. 01),left middle temporal gyrus/ superior temporal gyrus(t = 5. 06,P ﹤ 0. 01),the right precuneus/ cuneus (t = 3. 33,P ﹤ 0. 01),and the right superior parietal lo-bule(t = 3. 66,P ﹤ 0. 01),right precentral gyrus(t = 3. 44,P ﹤0. 01),right superior frontal gyrus/ paracentral lobule/ supplementary motor area(t = 3. 50,P ﹤ 0. 01). However,GMV increase was not found. Conclusions Brain GMV extensively decreased in 13 brain regions of IGE patients with typical absence seizure,and among them occipital lobe is the most significant.
