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In recent years, 3D fashion design has been relied on for improving attire fashion, design, and presentation with fewer flaws and better visualization. This aids consumers in providing visualized recommendations on modifications, suggestions, and customized attire designs. Considering the influence of automation and intelligent processing in the fashion designing industry, it introduces a Flaw Detection Method in 3D Representation (FDM-3DR) to reduce frequent modifications. The proposed method visualizes the design in three dimensions for its completeness and flawless representation. Based on the consumer recommendation, the lack of design flaws in the representation is identified, and multiple detections are presented. This is required to improve consumer satisfaction and the multi-dimensional projection between flaws and complete attire products. The learning is trained using the fixable representation, and therefore, the previous unsuitable designs are repelled by different recommendations. This improves the design adaptability, recommendation ratio, and representation ratio. Besides, it reduces the recommendation time and flaws.
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Here, we present the second generation of our bicyclic peptide library (NTB), featuring a stereodiversified structure and a simplified construction strategy. We utilized a tandem ring-opening metathesis and ring-closing metathesis reaction (ROM-RCM) to cyclize the linear peptide library in a single step, representing the first reported instance of this reaction being applied to the preparation of macrocyclic peptides. Moreover, the resulting bicyclic peptide can be easily linearized for MS/MS sequencing with a one-step deallylation process. We employed this library to screen against the E363-R378 epitope of MYC and identified several MYC-targeting bicyclic peptides. Subsequent in vitro cell studies demonstrated that one candidate, NT-B2R, effectively suppressed MYC transcription activities and cell proliferation.
Subject(s)
Peptide Library , Tandem Mass Spectrometry , Peptides/pharmacology , Peptides/chemistryABSTRACT
We analyzed the clinical characteristics of outpatients with influenza-B-associated pneumonia during the 2021-2022 influenza season and analyzed the molecular epidemiology and evolution of influenza B virus. The presence of influenza B virus was confirmed by reverse transcription polymerase chain reaction (RT-PCR). Electronic medical records were used to collect and analyze data of outpatients. The HA and NA genes were phylogenetically analyzed using ClustalW 2.10 and MEGA 11.0. Out of 1569 outpatients who tested positive for influenza B virus, 11.7% (184/1569) developed pneumonia, and of these, 19.0% (35/184) had underlying diseases. Fever, cough, and sore throat were the most common symptoms. Among the complications, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and shock accounted for 2.7% (5/184), 4.9% (9/184), and 1.6% (3/184), respectively. Of the outpatients, 2.7% (5/184) were admitted to the hospital, and 0.5% (1/184) of them died. All of the strains from Beijing were identified as belonging to the B/Victoria lineage. The HA and NA gene sequences of 41 influenza B viruses showed high similarity to each other, and all of them belonged to clade 1A.3. Compared with the vaccine strain B/Washington/02/2019, all of the isolates contained N150K, G181E, and S194D mutations. S194D, E195K, and K200R mutations were detected in the 190 helix of the receptor binding region of HA. Co-mutations of H122Q, A127T, P144L, N150K, G181E, S194D, and K200R in HA and D53N, N59S, and G233E in NA were detected in 78.0% (32/41) of the isolates, and 56.3% (18/32) of these were from outpatients with influenza-B-associated pneumonia. Influenza outpatients with underlying diseases were more likely to develop pneumonia. No significant differences were observed in clinical symptoms or laboratory results between outpatients with and without pneumonia, so testing for influenza virus seems to be a good choice. The observed amino acid variations suggest that current vaccines might not provide effective protection.
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Influenza, Human , Humans , Influenza, Human/epidemiology , Influenza B virus , Beijing , Seasons , Outpatients , Evolution, Molecular , Phylogeny , Hemagglutinin Glycoproteins, Influenza Virus/geneticsABSTRACT
OBJECTIVE@#To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism.@*METHODS@#Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis.@*RESULTS@#DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01).@*CONCLUSIONS@#DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Subject(s)
Mice , Male , Animals , Proto-Oncogene Proteins c-akt/metabolism , Lipopolysaccharides , Phosphatidylinositol 3-Kinases/metabolism , Interleukin-1beta/metabolism , Vascular Endothelial Growth Factor A/metabolism , Tumor Necrosis Factor-alpha/metabolism , Claudin-5/metabolism , Acute Lung Injury/chemically induced , Lung/pathology , Interleukin-6/metabolism , Drugs, Chinese HerbalABSTRACT
Objective To analyze the factors associated with pain after arthroscopic rotator cuff bridge suture.Methods According to the inclusion and exclusion criteria,the data of 112 patients with unilateral rotator cuff injury who received arthroscopic bridge suture in our department were collected and were investigated in the form of telephone follow-up.In this study,SPSS 23.0 was used to input data and conduct statistical analysis.Logistic regression analysis was used to analyze the correlation between the above influencing factors and postoperative pain.Results A total of 112 patients were included for statistical analysis,single factor analysis revealed,including course of disease,smoking history,preoperative University of California,Los Angeles(UCLA)score,Constant score,numeric rating scale(NRS),size of rotator cuff tear,whether it was full-thickness tear and degree of tendon retraction might be related to postoperative pain(P<0.05).The age,gender,body mass index(BMI),drinking history,diabetes and hypertension were not related to postoperative pain(P>0.05).Multiple linear regression analysis concluded that there were four factors related to postoperative pain,and the correlation degree was preoperative NRS,preoperative UCLA score,tear size and smoking history.Conclusion The causes of postoperative pain after arthroscopic rotator cauff repair are complex and diverse.Analyzing the cause of postoperative pain can effectively reduce the pain of patients and promote the recovery of shoulder joint function.
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Objective@#To explore the association between physical activity levels and depressive symptoms among college students, so as to provide evidence for promoting physical and mental health of college students.@*Methods@#Using a cohort study design,a baseline survey of 1 415 college students in Shenyang Normal University in 2017 followed for three years from 2018 to 2020. The International Physical Activity Questionnaire-Short Form (IPAQ-SF) and Selfrating Depression Scale (SDS) were used to evaluate the physical activity levels and depressive symptoms of college students. According to the level of physical activity at baseline (MET ·h/week), participants were divided into three groups [T1 (≤36.4), T2 (>36.4-89.3) and T3 (>89.3)]. Logistic regression analysis was used to examine the association between baseline physical activity levels and the incidence of depressive symptoms during the school years.@*Results@#In the 3year followup (2018-2020), 852 (60.2%) participants exhibited depressive symptoms. The numbers of individuals with depressive symptoms in the T1, T2, and T3 groups were 324, 268, and 260, respectively. Logistic regression analysis showed that college students who participated in higher levels of physical activity decreased the risk of depressive symptoms by 34.2% [T2: OR(95%CI) = 0.658 (0.500-0.866)] and 38.9% [T3:OR(95%CI)=0.611(0.465-0.804)] compared with T1 group after adjusting for demographic, lifestyle, healthrelated factors, and baseline depressive symptoms as covariates. The sexstratified analysis showed a negative correlation between physical activity levels and the incidence of depressive symptoms in female college students. Compared with T1 group, higher levels of physical activity reduced the incidence of depressive symptoms by 39.6% [T2: OR(95%CI)=0.604(0.445-0.820)] and 37.7% [T3: OR(95%CI)=0.623(0.459-0.846)], respectively (P<0.01). However, there was no significant correlation between physical activity levels and depressive symptoms in male college students (P>0.05).@*Conclusions@#There is an inverse relationship between physical activity levels and depressive symptoms. The findings suggest that schools should reduce the risk of depressive symptoms by promoting physical activity levels among college students.
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BACKGROUND: It is unknown whether total wrist arthrodesis (TWA) should be performed with or without arthrodesis of the carpometacarpal joint (CMCJ). The aim of this study is to compare CMCJ-spanning TWA plates using 3D printed wrist arthrodesis model with and without arthrodesis of the CMCJ. METHODS: Total wrist arthrodesis plates mounted to 3D printed models were tested under a 4-N bending load at 4 Hz for 50 000 cycles, increased by 15% every 10 000 cycles until failure. RESULTS: Plates with arthrodesis CMCJ were stiffer and failed at a significantly greater load and number of cycles than plates mounted to models without CMCJ arthrodesis. The Synthes stainless steel locking TWA plate performed better than the Trimed plate applied to the model without CMCJ arthrodesis and the Acumed plate applied to the model with CMCJ arthrodesis. Based on these findings, we recommend arthrodesis of the CMCJ in TWA. CONCLUSIONS: Incorporation of the CMCJ in TWA may protect against plate failure. If arthrodesis of the CMCJ is not performed, plate removal should be considered before breakage occurs. LEVEL OF EVIDENCE: IV.
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Multiplex protein imaging technologies enable deep phenotyping and provide rich spatial information about biological samples. Existing methods have shown great success but also harbored trade-offs between various pros and cons, underscoring the persisting necessity to expand the imaging toolkits. Here we present PACIFIC: photoactive immunofluorescence with iterative cleavage, a new modality of multiplex protein imaging methods. PACIFIC achieves iterative multiplexing by implementing photocleavable fluorophores for antibody labeling with one-step spin-column purification. PACIFIC requires no specialized instrument, no DNA encoding, or chemical treatments. We demonstrate that PACIFIC can resolve cellular heterogeneity in both formalin-fixed paraffin-embedded (FFPE) samples and fixed cells. To further highlight how PACIFIC assists discovery, we integrate PACIFIC with live-cell tracking and identify phosphor-p70S6K as a critical driver that governs U87 cell mobility. Considering the cost, flexibility, and compatibility, we foresee that PACIFIC can confer deep phenotyping capabilities to anyone with access to traditional immunofluorescence platforms.
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BACKGROUND: Influenza A viruses have undergone rapid evolution with virulent; however, complete and comprehensive data on gene evolution and amino acid variation of HA and NA in immunosuppressed patients was few. In this study, we analysed molecular epidemiology and evolution of influenza A viruses in immunosuppressed population, and immunocompetent population were used as controls. METHODS: Full sequences of HA and NA of A(H1N1)pdm09 and A(H3N2) were acquired through reverse transcription-polymerase chain reaction (RT-PCR). HA and NA genes were sequenced using the Sanger method and phylogenetically analysed using ClustalW 2.10 and MEGA software version 11.0. RESULTS: During the 2018-2020 influenza seasons, 54 immunosuppressed and 46 immunocompetent inpatients screened positive for influenza A viruses by using the quantitative real-time PCR (qRT-PCR) were enrolled. 27 immunosuppressed and 23 immunocompetent nasal swab or bronchoalveolar lavage fluid samples were randomly selected and sequenced using the Sanger method. A(H1N1)pdm09 were detected in 15 samples and the remaining 35 samples were A(H3N2) positive. By analyzing the HA and NA gene sequences of these virus strains, we found that all A(H1N1)pdm09 viruses shared high similarities to each other and the HA and NA genes of these viruses exclusively belonged to subclade 6B.1A.1. Some NA genes of A(H3N2) viruses were not in the same clade as those of A/Singapore/INFIMH-16-0019/2016 and A/Kansas/14/2017, which may have led to A(H3N2) being the dominant strain in the 2019-2020 influenza season. Both A(H1N1)pdm09 and A(H3N2) viruses showed similar evolutionary lineages patterns of HA and NA between immunosuppressed and immunocompetent patients. Compared with the vaccine strains, there were no statistically significant of HA and NA genes and amino acid sequences of influenza A viruses in immunosuppressed and immunocompetent patients. However, the oseltamivir resistance substitution of NA-H275Y and R292K have been observed in immunosuppressed patients. CONCLUSIONS: A(H1N1)pdm09 and A(H3N2) viruses showed similar evolutionary lineages patterns of HA and NA between immunosuppressed and immunocompetent patients. Both immunocompetent and immunosuppressed patients have some key substitutions, which should be of note monitored, especially those with potential to affect the viral antigen.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza, Human , Humans , Influenza A virus/genetics , Influenza, Human/epidemiology , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H3N2 Subtype/genetics , Phylogeny , Seasons , Inpatients , Beijing , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Neuraminidase/geneticsABSTRACT
Background: The monocyte-macrophage-dendritic cell (DC) (MMD) system exerts crucial functions that may modulate fibrogenesis in nonalcoholic steatohepatitis (NASH). In this study, we explored the cell characteristics, distribution and developmental trajectory of the liver MMD system in NASH mice with fibrosis and clarified characteristic genes of the MMD system involved in liver fibrosis progression in NASH mice and patients. Methods: Single cells in liver tissue samples from NASH and normal mice were quantified using single-cell RNA sequencing (scRNA-seq) analysis. Differentially expressed genes (DEGs) in the MMD system by pseudotime analysis were validated by tyramide signal amplification (TSA)-immunohistochemical staining (IHC) and analyzed by second harmonic generation (SHG)/two-photon excitation fluorescence (TPEF). Results: Compared with control mice, there were increased numbers of monocytes, Kupffer cells, and DCs in two NASH mouse models. From the transcriptional profiles of these single cells, we identified 8 monocyte subsets (Mono1-Mono8) with different molecular and functional properties. Furthermore, the pseudotime analysis showed that Mono5 and Mono6 were at the beginning of the trajectory path, whereas Mono2, Mono4, Kupffer cells and DCs were at a terminal state. Genes related to liver collagen production were at the late stage of this trajectory path. DEGs analysis revealed that the genes Fmnl1 and Myh9 in the MMD system were gradually upregulated during the trajectory. By TSA-IHC, the Fmnl1 and Myh9 expression levels were increased and associated with collagen production and fibrosis stage in NASH mice and patients. Conclusions: Our transcriptome data provide a novel landscape of the MMD system that is involved in advanced NASH disease status. Fmnl1 and Myh9 expression in the MMD system was associated with the progression of NASH fibrosis.
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Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/pathology , Monocytes/metabolism , Kupffer Cells/metabolism , Fibrosis , Gene ExpressionABSTRACT
BACKGROUND: This systematic review aims to explore the prevalence of the impact of the COVID-19, MERS, and SARS pandemics on the mental health of pregnant women. METHODS: All COVID-19, SARS and MERS studies that evaluated the mental health of pregnant women with/without gynaecological conditions that were reported in English between December 2000 - July 2021 were included. The search criteria were developed based upon the research question using PubMed, Science Direct, Ovid PsycINFO and EMBASE databases. A wide search criterion was used to ensure the inclusion of all pregnant women with existing gynaecological conditions. The Newcastle-Ottawa-Scale was used to assess the risk of bias for all included studies. Random effects model with restricted maximum-likelihood estimation method was applied for the meta-analysis and I-square statistic was used to evaluate heterogeneity across studies. The pooled prevalence rates of symptoms of anxiety, depression, PTSD, stress, and sleep disorders with 95% confidence interval (CI) were computed. RESULTS: This systematic review identified 217 studies which included 638,889 pregnant women or women who had just given birth. There were no studies reporting the mental health impact due to MERS and SARS. Results showed that women who were pregnant or had just given birth displayed various symptoms of poor mental health including those relating to depression (24.9%), anxiety (32.8%), stress (29.44%), Post Traumatic Stress Disorder (PTSD) (27.93%), and sleep disorders (24.38%) during the COVID-19 pandemic. DISCUSSION: It is important to note that studies included in this review used a range of outcome measures which does not allow for direct comparisons between findings. Most studies reported self-reported measure of symptoms without clinical diagnoses so conclusions can be made for symptom prevalence rather than of mental illness. The importance of managing mental health during pregnancy and after-delivery improves the quality of life and wellbeing of mothers hence developing an evidence-based approached as part of pandemic preparedness would improve mental health during challenging times. OTHER: The work presented in this manuscript was not funded by any specific grants. A study protocol was developed and published in PROSPERO (CRD42021235356) to explore several key objectives.
Subject(s)
COVID-19 , Sleep Wake Disorders , Female , Pregnancy , Humans , Mental Health , Pandemics , COVID-19/epidemiology , Prevalence , Quality of Life , Parturition , Anxiety/epidemiology , Sleep Wake Disorders/epidemiology , Depression/epidemiologyABSTRACT
Objective:To explore the effect of perioperative aspirin administration on intraoperative and postoperative bleeding in patients undergoing video-assisted thoracoscopic (VATS) pulmonary wedge resection.Methods:Sixty-three patients scheduled for VATS pulmonary wedge resection in Shougang Hospital of Peking University from November 2020 to April 2022 were randomly assigned in 2 groups. All patients had a history of aspirin taking, patients in study group ( n=32) continued aspirin taking perioperatively, and patients in the control group ( n=31) stopped taking aspirin for 7 days before surgery and resumed taking 3 days after surgery. The volume of intraoperative blood lost, operation time, postoperative drainage volume, thoracic drainage tube placement time, postoperative hospital stay, postoperative thrombosis of lower extremity, perioperative cardiovascular and cerebrovascular events, and postoperative wound healing were documented and compared between the two groups. Results:There were no significant differences in age, gender, oral aspirin time, lesion location, lesion nature, localization, lesion size and underlying disease between the two groups (all P>0.05). All patients successfully completed the operation, and no patients switched to thoracotomy. The intraoperative blood loss in study group and control group was (27.72±12.86) ml and (31.35±13.81) ml ( t=1.08, P=0.283); the operation time was (61.16±10.24) minutes and (61.39±13.79) minutes, respectively ( t=0.08, P=0.940). There were no significant differences in postoperative thoracic drainage, drainage tube placement time, length of hospital stay, incidence of lower extremity thrombosis, incidence of cardiovascular and cerebrovascular events, and rate of poor wound healing between the two groups (all P>0.05). Conclusion:Perioperative administration of aspirin may not increase intraoperative and postoperative bleeding, and the incidence of operation-related complications in patients undergoing VATS pulmonary wedge resection.
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AIM: To investigate the changes in retinal nerve fiber layer(RNFL)and macular retinal thickness(MRT)in children with refractive abnormalities and amblyopia, and their predictive value of outcome.METHODS: A total of 168 children with myopic refractive abnormalities and monocular amblyopia admitted to our hospital from January 2020 to October 2022 were selected as the observation group, with 118 cases of mild to moderate amblyopia and 50 cases of severe amblyopia, and 168 children with normal vision were included as the control group in a 1:1 ratio during the same period. The changes of RNFL and MRT in two groups of children were statistically counted, and the correlation between the severity of refractive abnormalities and RNFL and MRT in children with amblyopia was analyzed. Additionally, the observation group was divided into effective subgroup and ineffective subgroup based on the therapeutic effect. The general information, as well as RNFL and MRT of the effective subgroup and the ineffective subgroups before and after treatment were compared. Logistic was used to analyze the factors influencing efficacy, and ROC curves was plotted to analyze the predictive value of RNFL and MRT alone or in combination for efficacy.RESULTS: RNFL and MRT of cases of severe amblyopia were higher than those of the mild to moderate amblyopia and the control groups(all P&#x003C;0.05); the severity of amblyopia in children with refractive abnormalities is positively correlated with RNFL and MRT(rs=0.745 and0.724, both P&#x003C;0.001); among patients of mild to moderate and severe, there were statistically significant differences between the effective and ineffective subgroups in terms of initial treatment age, fixation form, treatment compliance, as well as RNFL, MRT, and their differences before and 1mo postoperatively(all P&#x003C;0.05). Logistic analysis showed that initial treatment age, fixation nature, treatment compliance, RNFL and MRT before and 1mo postoperatively were all factors influencing the therapeutic effect of amblyopia with refractive abnormalities in children(all P&#x003C;0.05); after 1mo of treatment, the combined prediction of RNFL and MRT was significantly better than that of single prediction in children with mild to severe amblyopia.CONCLUSION:There are differences in RNFL and MRT in children with abnormal refractive amblyopia, and they are closely related to the different degrees and curative effects of children. The combination of RNFL and MRT after 1mo of treatment has certain value in predicting children with different degrees of abnormal refractive amblyopia.
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This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1β, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.
Subject(s)
Animals , Rats , Caspase 1/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Interleukin-18 , Blood Glucose , Pyroptosis , Tumor Necrosis Factor-alpha , Diabetes Complications , Vascular Diseases , Inflammasomes , Cholesterol , Lipids , Diabetes MellitusABSTRACT
This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1ß, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.
Subject(s)
Diabetes Complications , Diabetes Mellitus , Vascular Diseases , Animals , Rats , Caspase 1/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Interleukin-18 , Blood Glucose , Pyroptosis , Tumor Necrosis Factor-alpha , Inflammasomes , Cholesterol , LipidsABSTRACT
Delivering cargo molecules across the plasma membrane is critical for biomedical research, and the need to develop molecularly well-defined tags that enable cargo transportation is ever-increasing. We report here a hydrophilic endocytosis-promoting peptide (EPP6) rich in hydroxyl groups with no positive charge. EPP6 can transport a wide array of small-molecule cargos into a diverse panel of animal cells. Mechanistic studies revealed that it entered the cells through a caveolin- and dynamin-dependent endocytosis pathway, mediated by the surface receptor fibrinogen C domain-containing protein 1. After endocytosis, EPP6 trafficked through early and late endosomes within 30 min. Over time, EPP6 partitioned among cytosol, lysosomes, and some long-lived compartments. It also demonstrated prominent transcytosis abilities in both in vitro and in vivo models. Our study proves that positive charge is not an indispensable feature for hydrophilic cell-penetrating peptides and provides a new category of molecularly well-defined delivery tags for biomedical applications.
Subject(s)
Cell-Penetrating Peptides , Endocytosis , Animals , Endosomes/metabolism , Cell-Penetrating Peptides/metabolism , Lysosomes/metabolism , Hydrophobic and Hydrophilic InteractionsABSTRACT
Background: Although effective vaccines have been developed against coronavirus disease 2019 (COVID-19), the level of neutralizing antibodies (NAbs) induced after vaccination in the real world is still unknown. The aim of this work was to evaluate the level and persistence of NAbs induced by two inactivated COVID-19 vaccines in China. Methods: Serum samples were collected from 1,335 people aged 18 years and over who were vaccinated with an inactivated COVID-19 vaccine at Peking University People's Hospital from January 19 to June 23, 2021, for the detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Results: The positive rate for NAbs against SARS-CoV-2 was 79-91% from the first month to the second month after the second vaccine dose. The gradual decline in positivity rate for NAb response was observed from 78% at 3 months post-vaccination to 0% at 12 months post-vaccination. When there was a 21-day interval between the two doses of vaccine, the NAb positivity rate was 0% 6 months after the second dose. NAb levels were significantly higher when the interval between two doses were 3-8 weeks than when it was 0-3 weeks (χ2 = 14.04, p < 0.001). There was a linear correlation between NAbs and IgG antibodies in 1,335 vaccinated patients. NAb levels decreased in 31 patients (81.6%) and increased in 7 patients (18.4%) over time in the series of 38 patients after the second vaccination. The NAb positivity rate was significantly higher in 18- to 40-year-old subjects than in 41- to 60-year-old subjects (t = -1.959, p < 0.01; t = 0.839, p < 0.01). Conclusion: The NAb positivity rate was the highest at the first and second month after the second dose of vaccine, and gradually decreased over time. With a 21-day interval between two doses of vaccine, neutralizing antibody levels persisted for only 6 months after the second dose of vaccine. Therefore, a third vaccine dose is recommended. Our results suggest that in cases in which NAbs cannot be detected, IgM/IgG antibodies can be detected instead. The level of NAbs produced after vaccination was affected by age but not by sex. Our results suggest that an interval of 21 to 56 days between shots is suitable for vaccination.
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BACKGROUND: Compared with immunocompetent patients, immunosuppressed patients have higher morbidity and mortality, a longer duration of viral shedding, more frequent complications, and more antiviral resistance during influenza infections. However, few data on this population in China have been reported. We analysed the clinical characteristics, effects of antiviral therapy, and risk factors for admission to the intensive care unit (ICU) and death in this population after influenza infections and explored the influenza vaccination situation for this population. METHODS: We analysed 111 immunosuppressed inpatients who were infected with influenza virus during the 2015-2020 influenza seasons. Medical data were collected through the electronic medical record system and analysed. Univariate analysis and multivariate logistics analysis were used to identify risk factors. RESULTS: The most common cause of immunosuppression was malignancies being treated with chemotherapy (64.0%, 71/111), followed by haematopoietic stem cell transplantation (HSCT) (23.4%, 26/111). The most common presenting symptoms were fever and cough. Dyspnoea, gastrointestinal symptoms and altered mental status were more common in HSCT patients than in patients with immunosuppression due to other causes. Approximately 14.4% (16/111) of patients were admitted to the ICU, and 9.9% (11/111) of patients died. Combined and double doses of neuraminidase inhibitors did not significantly reduce the risk of admission to the ICU or death. Risk factors for admission to the ICU were dyspnoea, coinfection with other pathogens and no antiviral treatment within 48 h. The presence of dyspnoea and altered mental status were independently associated with death. Only 2.7% (3/111) of patients less than 12 months old had received a seasonal influenza vaccine. CONCLUSION: Fever and other classic symptoms of influenza may be absent in immunosuppressed recipients, especially in HSCT patients. Conducting influenza virus detection at the first presentation seems to be a good choice for early diagnosis. Clinicians should pay extra attention to immunosuppressed patients with dyspnoea, altered mental status, coinfection with other pathogens and no antiviral treatment within 48 h because these patients have a high risk of severe illness. Inactivated influenza vaccines are recommended for immunosuppressed patients.
Subject(s)
Influenza Vaccines , Influenza, Human , Antiviral Agents/therapeutic use , Beijing , Humans , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Inpatients , Risk Factors , SeasonsABSTRACT
Objective:To study the influencing factors for shoulder stiffness after rotator cuff tear.Methods:The data of 228 patients were retrospectively analyzed who had been diagnosed with rotator cuff tear by arthroscopic surgery at Department of Articular Surgery, Hospital Affiliated to Chengde Medical College from June 2019 to May 2021. Their baseline data were recorded immediately after admission, including possible risk factors for shoulder stiffness. The patients were divided into a stiffness group and a non-stiffness group based on passive range of motion of shoulder joint. Univariate and multivariate analyses were performed to find out the influencing factors for shoulder stiffness after rotator cuff tear.Results:Preliminary univariate analysis showed that advanced age, smoking history, misdiagnosis history, no standardized physiotherapy history, high body mass index (BMI) and long duration of disease were all likely risk factors for shoulder stiffness in patients with rotator cuff tear ( P<0.05). Multivariate analysis confirmed that advanced age( OR=1.474, 95% CI: 1.013~2.145, P=0.043), smoking history( OR=2.239, 95% CI: 1.147~4.368, P=0.018), no standardized physiotherapy history( OR=0.167, 95% CI: 0.065~0.424, P<0.001), high BMI( OR=3.029, 95% CI: 1.657~5.536, P<0.001) and long duration of disease ( OR=1.775, 95% CI: 1.384~2.276, P<0.001) were the risk factors for shoulder stiffness. Conclusion:Age>60 years, smoking history, misdiagnosis history, no standardized physiotherapy history, high body mass index and long course of disease may be the important influencing factors for shoulder stiffness after rotator cuff tear.
ABSTRACT
Polarity-reversal catalysts enable otherwise sluggish or completely ineffective reactions which are characterized by unfavorable polar effects between radicals and substrates. We herein disclose that when irradiated by visible light, bromine can behave as a polarity-reversal catalyst. Hydroacylation of vinyl arenes, a three-component cascade transformation and deuteration of aldehydes were each achieved in a metal-free manner without initiators by using inexpensive N-bromosuccinimide as the precatalyst. Light is essential to generate and maintain the active bromine radical during the reaction process. Another key to success is that HBr can behave as an effective hydrogen donor to turn over the catalytic cycles.