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OBJECTIVE@#To analyze the mutations in transcription regulatory sequences (TRSs) of coronaviruss (CoV) to provide the basis for exploring the patterns of SARS-CoV-2 transmission and outbreak.@*METHODS@#A combined evolutionary and molecular functional analysis of all sets of publicly available genomic data of viruses was performed.@*RESULTS@#A leader transcription regulatory sequence (TRS-L) usually comprises the first 60-70 nts of the 5' UTR in a CoV genome, and the body transcription regulatory sequences (TRS-Bs) are located immediately upstream of the genes other than ORF1a and 1b. In each CoV genome, the TRS-L and TRS-Bs share a specific consensus sequence, namely the TRS motif. Any changes of nucleotide residues in the TRS motifs are defined as TRS motif mutations. Mutations in the TRS-L or multiple TRS-Bs result in superattenuated variants. The spread of super-attenuated variants may cause an increase in asymptomatic or mild infections, prolonged incubation periods and a decreased detection rate of the viruses, thus posing new challenges to SARS-CoV-2 prevention and control. The super-attenuated variants also increase their possibility of long-term coexistence with humans. The Delta variant is significantly different from all the previous variants and may lead to a large-scale transmission. The Delta variant (B.1.617.2) with TRS motif mutation has already appeared and shown signs of spreading in Singapore, which, and even the Southeast Asia, may become the new epicenter of the next wave of SARS-CoV-2 outbreak.@*CONCLUSION@#TRS motif mutation will occur in all variants of SARS-CoV-2 and may result in super-attenuated variants. Only super-attenuated variants with TRS motif mutations will eventually lose the abilities of cross-species transmission and causing outbreaks.
Subject(s)
Humans , COVID-19/virology , Genome, Viral , Mutation , SARS-CoV-2/geneticsABSTRACT
BACKGROUND@#Surface modification is used to modify the biomaterials for the regulation of cell culture using different approaches, such as chemical graft and mechanical treatment. However, those conventional methodologies often require precise fabrication in a high resolution involving either high cost or laborious steps to remove chemical residues that are toxic to the cells. @*METHODS@# A novel and simple method was proposed and evaluated to rapidly generate surface ceases on the gelatin methacrylate (gelMA) surface using the heating-hydration process. Human umbilical vein endothelial cells (HUVECs) were cultured on the gelMA surface. The surface binding was characterized using the RGD (Arg-Gly-Asp) antibodies and cell adhesion pattern captured by scanning electron microscopy. The effect of the heating-hydration parameters on the creasing formation was investigated. The morphology of HUVECs cultured on such micropatterned gelMA was characterized and compared. @*RESULTS@#It is found that the hydration solution, gelMA mixture, and hydration rate are the major factors that influence the cracking sizes in the range from 20 to 120 lm which resulted in capillary-like patterns on the gelMA surface. Low concentration of gelMA, high water concentration of cooling agent, and slow hydration rate result in the long creases, and heating of at least 60 min is required for complete dehydration. Strong fluorescence was around the creases with RGDstaining. Consequently, micropatterned gelMA demonstrated good biocompatibility with endothelial cells with more than 95% cell viability and continuous cell proliferation throughout 2 weeks as well as a good trace of neovascular formation. In comparison, normal gelMA surface did not exhibit RGD-fluorescent signals, and the cultured HUVECs on it were rounded with no spreading for network formation. @*CONCLUSION@#The heating-hydration approach can successfully and easily produce the micropatterned gelMA that allows rapid and effective vascularization to potentially improve the functionalities of the tissue-engineered construct.
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BACKGROUND@#Surface modification is used to modify the biomaterials for the regulation of cell culture using different approaches, such as chemical graft and mechanical treatment. However, those conventional methodologies often require precise fabrication in a high resolution involving either high cost or laborious steps to remove chemical residues that are toxic to the cells. @*METHODS@# A novel and simple method was proposed and evaluated to rapidly generate surface ceases on the gelatin methacrylate (gelMA) surface using the heating-hydration process. Human umbilical vein endothelial cells (HUVECs) were cultured on the gelMA surface. The surface binding was characterized using the RGD (Arg-Gly-Asp) antibodies and cell adhesion pattern captured by scanning electron microscopy. The effect of the heating-hydration parameters on the creasing formation was investigated. The morphology of HUVECs cultured on such micropatterned gelMA was characterized and compared. @*RESULTS@#It is found that the hydration solution, gelMA mixture, and hydration rate are the major factors that influence the cracking sizes in the range from 20 to 120 lm which resulted in capillary-like patterns on the gelMA surface. Low concentration of gelMA, high water concentration of cooling agent, and slow hydration rate result in the long creases, and heating of at least 60 min is required for complete dehydration. Strong fluorescence was around the creases with RGDstaining. Consequently, micropatterned gelMA demonstrated good biocompatibility with endothelial cells with more than 95% cell viability and continuous cell proliferation throughout 2 weeks as well as a good trace of neovascular formation. In comparison, normal gelMA surface did not exhibit RGD-fluorescent signals, and the cultured HUVECs on it were rounded with no spreading for network formation. @*CONCLUSION@#The heating-hydration approach can successfully and easily produce the micropatterned gelMA that allows rapid and effective vascularization to potentially improve the functionalities of the tissue-engineered construct.
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Henoch-schonlein purpura is the most common vasculitis in the childhood.The prognosis of Henoch-schonlein purpura is mainly dependent on the renal component of the disease, which is equal to the severity of Henoch-schonlein purpura nephritis(HSPN). To predict the outcome of the HSPN, the pathology of renal biopsy is still remaining the gold standard.The conventional histological classification of the International Study of Kidney Disease in Chlidren(ISKDC), which is facing severe challenges in evaluating the prognosis of the HSPN, is imprecise.So it′s very necessary to recognize the relationship between specific pathological changes and prognosis of HSPN.So we reviewed the relationship between specific pathological changes and the prognosis prediction of HSPN in this paper, hoping to guide the clinical work.
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BACKGROUND AND OBJECTIVE@#Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice.@*METHODS@#Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively.@*RESULTS@#A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition.@*CONCLUSIONS@#In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.
Subject(s)
Animals , Male , Mice , Dexamethasone/therapeutic use , Disease Models, Animal , Kupffer Cells/physiology , Liver Failure, Acute/pathology , Mice, Inbred C57BL , Nuclear Receptor Subfamily 4, Group A, Member 1/physiology , Receptors, Glucocorticoid/physiologyABSTRACT
Objective To understand the thyroid stimulating hormone (TSH) level of neonates and iodine nutritional status of pregnant women and children in Guizhou Province.Metheds From 2016 to 2017,a city (district,county) in government location in Guizhou Province was selected as the urban survey site,and a county (city,district) whose economy was relatively backward and farther from the city (prefecture) in government location was selected as the rural survey site.In each survey site,300 salt samples were collected for determination of salt iodine;300 blood samples in the heel of neonates after birth 72 hours were taken for measurement of TSH.The Wodd Health Organization,United Nations International Children's Emergency Fund,and the International Committee for the Control of Iodine Deficiency (WHO/UNICEF/ICCIDD) recommend that when the proportion of neonates (TSH levels ＞ 5 mU/L) is ＜ 3％,the area is non-iodine-deficient.In other words,the 97th percentile (P97) value should be ≤5 mU/L.The normal reference value of the kit is ≤9 mU/L.And urinary iodine of 150 children aged 8-10 and 150 pregnant women was determined.Results A total of 5 400 edible salt samples were tested,the median of salt iodine was 27.9 mg/kg,and the consumption rate of qualified iodized salt was 94.89％ (5 124/5 400);5 400 neonatal heel blood samples were collected,the median of TSH was 2.62 mU/L,TSH P97 was 6.91 mU/L,and samples proportion with TSH ＞ 5 mU/L was 10.67％ (576/5 400),and ＞ 9 mU/L (the cut-off value of kit) was 1.00％ (54/5 400).Among 3 588 cases of children aged 8 to 10 years,the median of urinary iodine was 212.3 μg/L,those with urinary iodine ＜ 50 μg/L was 2.81％ (101/3 588),and ＜ 100 μg/L was 12.76％ (458/3 588).Among the 2 695 pregnant women,the median of urinary iodine was 163.1 μg/L,and 44.04％ (1 187/2 695) were ＜ 150 μg/L.Conclusions The quality of iodized salt is stable in Guizhou,the iodine nutrition status of children and pregnant women are good.The neonatal TSH and nutritional status of pregnant women should be monitored in the future.
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Objective To explore the working mode of continuous malaria elimination. Methods Judong Village in Congjiang County, Guizhou Province, which had the highest record of malaria incidence in the history of Guizhou Province, was selected as a pilot, a comprehensive prevention and control intervention was carried out aiming at the malaria epidemic, transmission and influencing factors, and the effect was evaluated after the intervention. Results From 2015 to 2016, through those intensive measures of constructing system, improving environment and health education, the people’s awareness of malaria prevention was increased, the people’s enthusiasm and initiatives to participate in the prevention and control of malaria were improved in Judong Village. Meanwhile, the roads were hardened and beautified, the dispose of sewage, feces and garbage was centralized. The awareness rate of malaria prevention knowledge of residents increased to 85% to 95%, and the formation rate of anti-mosquito behavior increased to 89.66%. The density of media Anopheles reduced from 0.56 to 0.07 mosquitoes per hour each mosquito catching platform. Conclusion A long-term mechanism for malaria prevention and control has been almost constructed in Judong Village, which facilitates the consolidation of malaria control achievements, and the progress towards malaria elimination.
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Objective To explore the working mode of continuous malaria elimination. Methods Judong Village in Congjiang County, Guizhou Province, which had the highest record of malaria incidence in the history of Guizhou Province, was selected as a pilot, a comprehensive prevention and control intervention was carried out aiming at the malaria epidemic, transmission and influencing factors, and the effect was evaluated after the intervention. Results From 2015 to 2016, through those intensive measures of constructing system, improving environment and health education, the people’s awareness of malaria prevention was increased, the people’s enthusiasm and initiatives to participate in the prevention and control of malaria were improved in Judong Village. Meanwhile, the roads were hardened and beautified, the dispose of sewage, feces and garbage was centralized. The awareness rate of malaria prevention knowledge of residents increased to 85% to 95%, and the formation rate of anti-mosquito behavior increased to 89.66%. The density of media Anopheles reduced from 0.56 to 0.07 mosquitoes per hour each mosquito catching platform. Conclusion A long-term mechanism for malaria prevention and control has been almost constructed in Judong Village, which facilitates the consolidation of malaria control achievements, and the progress towards malaria elimination.
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Objective To understand the status of total fluoride intake for persons over 16 years old after implementation of comprehensive prevention and control measures in historical severe diseased areas of coal-burning-borne endemic fluorosis in Guizhou Province.Methods In 2017,a total of 3 villages were selected as survey sites in Hehua,Jifeng and Jiping villages,which were heavier and did not meet the standards for elimination of the disease areas.Dental fluorosis of all children aged 8-12 were examined in these three villages.In each village,10 households were selected and average daily intake of staple foods,vegetables and drinking water per person over 16 years of age were surveyed.Samples of corn,rice,dried pepper,drinking water,and indoor air were collected and the content of fluoride was measured,and total fluoride intakes for adults were calculated.The survey results were compared with the survey data of 2006.Results The detection rates of dental fluorosis of children aged 8-12 in Hehua,Jifeng and Jiping were 16.86％ (29/172),17.90％ (29/162),7.94％ (10/126),respectively,and the differences were statistically significant compared to those of 2006 [94.32％ (216/229),100.00％ (72/72)、99.63％ (267/268),x2 =247.97,136.95,345.13,P ＜ 0.01].The fluorosis indices were 0.36,0.40,and 0.12,respectively.In the three villages,the medians of fluoride in drinking water were 0.040,0.029 and 0.033 mg/L.The staple food was rice,and their medians fluorine content were 0.019,0.016,and 0.015 mg/kg,respectively,which decreased 99.89％,99.96％,99.95％,compared with those of 2006 (the staple food was corn,with medians of 17.520,36.620 and 27.770 mg/kg).The medians of fluorine in dried pepper were 2.09,1.97 and 0.35 mg/kg,respectively,which decreased 99.59％,99.81％,99.96％,respectively,compared with those of 2006 (514.21,1 035.29,947.78 mg/kg),the differences were statistically significant (Z =2.079,2.542,2.449,P ＜ 0.01).No fluoride was detected in indoor air samples 24 hours a day.The average daily intake of fluorine per person over 16 years in the three villages were 0.304,0.279,0.273 mg,which decreased 98.45％,99.18％ and 99.00％,respectively compared to those of 2006 (19.564,33.837,27.224 mg).Conclusion Total fluoride levels are significantly lower in people over 16 years of age in the historical severe disease areas of coal-burning-borne endemic fluorosis in Guizhou Province.
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Background@#Obstructive sleep apnea syndrome (OSAS) is prevalent in obesity and is associated with many metabolic abnormalities. The relationship between OSAS and bone metabolism is still unclear. The aim of this study was to investigate the relationship between the severity of OSAS and bone metabolic markers.@*Methods@#A total of 119 obese males were enrolled in this study in spring months from 2015 to 2017. All candidates underwent polysomnography, and their bone mineral density (BMD) and the serum levels of total procollagen type 1 N-terminal propeptide (t-P1NP), N-terminal midfragment of osteocalcin (N-MID), β-C-terminal telopeptide of type 1 collagen (β-CTX), vitamin D (VD), and parathyroid hormone (PTH) were measured. The analysis of variance and Pearson correlation analysis were performed for data analyses.@*Results@#No significant differences in the mean values of BMD were observed among the obesity, mild-to-moderate OSAS, and severe OSAS groups; and the serum levels of t-P1NP and β-CTX in the severe OSAS group were significantly higher than those in the obesity group (48.42 ± 23.78 ng/ml vs. 31.98 ± 9.85 ng/ml, P < 0.001; 0.53 ± 0.24 ng/ml vs. 0.41 ± 0.13 ng/ml, P = 0.011, respectively). The serum level of VD in the obesity group was significantly higher than those in the mild-to-moderate and severe OSAS groups (both P < 0.001), and decreased as the severity of OSAS increased (P < 0.001). The serum level of PTH in the severe OSAS group was significantly higher than those in the obesity and mild-to-moderate OSAS groups (both P < 0.001). The results of correlation analysis indicated that the level of apnea-hypopnea index (AHI) was correlated with the levels of t-P1NP (r = 0.396, P < 0.001), VD (r = -0.404, P < 0.001), and PTH (r = 0.400, P < 0.001), whereas the level of minimum Osaturation (SaOmin) was correlated with the levels of VD (r = 0.258, P = 0.016) and PTH (r = -0.376, P < 0.001).@*Conclusions@#The levels of bone resorption and formation markers in patients with severe OSAS were significantly increased compared to obese men, and the severity of OSAS was correlated with the serum levels of t-P1NP, VD, and PTH.