Clinical activity and safety of sintilimab, bevacizumab, and TMZ in patients with recurrent glioblastoma.

PURPOSE: There are limited and no standard therapies for recurrent glioblastoma. We herein report the antitumour activity and safety of sintilimab, bevacizumab and temozolomide (TMZ) in recurrent glioblastoma. METHODS: We retrospectively analysed eight patients with recurrent glioblastoma treated with sintilimab (200 mg) every three weeks + bevacizumab (10 mg/kg) every three weeks + TMZ (200 mg/m²orally) (5 days orally every 28 days for a total of four weeks). The primary objective was investigator-assessed median progression-free survival(mPFS). Secondary objectives were to assess the 6-month PFS, objective response rate (ORR) and duration of response (DOR) accroding to RANO criteria. RESULTS: The mPFS time for 8 patients was 3.340 months (95% CI: 2.217-4.463), The longest PFS was close to 9 months. Five patients were assessed to have achieved partial response (PR), with an overall remission rate of 62.5%, Four patients experienced a change in tumour volume at the best response time of greater than 60% shrinkage from baseline, and one patient remained progression free upon review, with a DOR of more than 6.57 months. The 6-month PFS was 25% (95% CI: 5.0-55.0%). Three patients had a treatment-related adverse events, though no grade 4 or 5 adverse events occurred. CONCLUSION: In this small retrospective study, the combination regimen of sintilimab, bevacizumab and TMZ showed promising antitumour activity in treatment of recurrent glioblastoma, with a good objective remission rate.

Amide proton transfer weighted and diffusion weighted imaging based radiomics classification algorithm for predicting 1p/19q co-deletion status in low grade gliomas.

BACKGROUND: 1p/19q co-deletion in low-grade gliomas (LGG, World Health Organization grade II and III) is of great significance in clinical decision making. We aim to use radiomics analysis to predict 1p/19q co-deletion in LGG based on amide proton transfer weighted (APTw), diffusion weighted imaging (DWI), and conventional MRI. METHODS: This retrospective study included 90 patients histopathologically diagnosed with LGG. We performed a radiomics analysis by extracting 8454 MRI-based features form APTw, DWI and conventional MR images and applied a least absolute shrinkage and selection operator (LASSO) algorithm to select radiomics signature. A radiomics score (Rad-score) was generated using a linear combination of the values of the selected features weighted for each of the patients. Three neuroradiologists, including one experienced neuroradiologist and two resident physicians, independently evaluated the MR features of LGG and provided predictions on whether the tumor had 1p/19q co-deletion or 1p/19q intact status. A clinical model was then constructed based on the significant variables identified in this analysis. A combined model incorporating both the Rad-score and clinical factors was also constructed. The predictive performance was validated by receiver operating characteristic curve analysis, DeLong analysis and decision curve analysis. P < 0.05 was statistically significant. RESULTS: The radiomics model and the combined model both exhibited excellent performance on both the training and test sets, achieving areas under the curve (AUCs) of 0.948 and 0.966, as well as 0.909 and 0.896, respectively. These results surpassed the performance of the clinical model, which achieved AUCs of 0.760 and 0.766 on the training and test sets, respectively. After performing Delong analysis, the clinical model did not significantly differ in predictive performance from three neuroradiologists. In the training set, both the radiomic and combined models performed better than all neuroradiologists. In the test set, the models exhibited higher AUCs than the neuroradiologists, with the radiomics model significantly outperforming resident physicians B and C, but not differing significantly from experienced neuroradiologist. CONCLUSIONS: Our results suggest that our algorithm can noninvasively predict the 1p/19q co-deletion status of LGG. The predictive performance of radiomics model was comparable to that of experienced neuroradiologist, significantly outperforming the diagnostic accuracy of resident physicians, thereby offering the potential to facilitate non-invasive 1p/19q co-deletion prediction of LGG.

O-glycosylation of SARS-CoV-2 spike protein by host O-glycosyltransferase strengthens its trimeric structure.

Protein O-glycosylation, also known as mucin-type O-glycosylation, is one of the most abundant glycosylation in mammalian cells. It is initially catalyzed by a family of polypeptide GalNAc transferases (ppGalNAc-Ts). The trimeric spike protein (S) of SARS-CoV-2 is highly glycosylated and facilitates the virus's entry into host cells and membrane fusion of the virus. However, the functions and relationship between host ppGalNAc-Ts and O-glycosylation on the S protein remain unclear. Herein, we identify 15 O-glycosites and 10 distinct O-glycan structures on the S protein using an HCD-product-dependent triggered ETD mass spectrometric analysis. We observe that the isoenzyme T6 of ppGalNAc-Ts (ppGalNAc-T6) exhibits high O-glycosylation activity for the S protein, as demonstrated by an on-chip catalytic assay. Overexpression of ppGalNAc-T6 in HEK293 cells significantly enhances the O-glycosylation level of the S protein, not only by adding new O-glycosites but also by increasing O-glycan heterogeneity. Molecular dynamics simulations reveal that O-glycosylation on the protomer-interface regions, modified by ppGalNAc-T6, potentially stabilizes the trimeric S protein structure by establishing hydrogen bonds and non-polar interactions between adjacent protomers. Furthermore, mutation frequency analysis indicates that most O-glycosites of the S protein are conserved during the evolution of SARS-CoV-2 variants. Taken together, our finding demonstrate that host O-glycosyltransferases dynamically regulate the O-glycosylation of the S protein, which may influence the trimeric structural stability of the protein. This work provides structural insights into the functional role of specific host O-glycosyltransferases in regulating the O-glycosylation of viral envelope proteins.

Why do Chinese Youth Seek Cancer Risk Information Online? Evidence from Four Cities.

This study, inspired by the Risk Information Seeking and Processing (RISP) model, examines the mechanisms by which perceived hazard characteristics and the informational subjective norms of Chinese youth, aged from 14 to 44 years old, become associated with their intentions to seek cancer risk information online. A sample of 684 Chinese youths was collected from four cities in Mainland China with results revealing that perceived hazard characteristics and informational subjective norms motivate their online cancer risk information seeking intentions. Specifically, perceived probability, perceived severity, and institutional trust are positively related to negative affect, however the relationship between personal control and negative affect is not significant. Institutional trust and personal control are positively related to positive affect while perceived probability and perceived severity have no significant effect on positive affect. Negative affect and informational subjective norms are positively related to perceived information insufficiency, while the relationship between positive affect and perceived information insufficiency is not significant. Negative affect, positive affect, informational subjective norms, and perceived information insufficiency are all positively related to the online cancer risk information seeking intentions of Chinese youth.

Automated detection and segmentation of pleural effusion on ultrasound images using an Attention U-net.

BACKGROUND: Ultrasonic for detecting and evaluating pleural effusion is an essential part of the Extended Focused Assessment with Sonography in Trauma (E-FAST) in emergencies. Our study aimed to develop an Artificial Intelligence (AI) diagnostic model that automatically identifies and segments pleural effusion areas on ultrasonography. METHODS: An Attention U-net and a U-net model were used to detect and segment pleural effusion on ultrasound images of 848 subjects through fully supervised learning. Sensitivity, specificity, precision, accuracy, F1 score, the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) were used to assess the model's effectiveness in classifying the data. The dice coefficient was used to evaluate the segmentation performance of the model. RESULTS: In 10 random tests, the Attention U-net and U-net 's average sensitivity of 97% demonstrated that the pleural effusion was well detectable. The Attention U-net performed better at identifying negative images than the U-net, which had an average specificity of 91% compared to 86% for the U-net. Additionally, the Attention U-net was more accurate in predicting the pleural effusion region because its average dice coefficient was 0.86 as opposed to the U-net's average dice coefficient of 0.82. CONCLUSIONS: The Attention U-net showed excellent performance in detecting and segmenting pleural effusion on ultrasonic images, which is expected to enhance the operation and application of E-FAST in clinical work.

Improving cascade outcomes for active TB: A global systematic review and meta-analysis of TB interventions.

BACKGROUND: To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. METHODS AND FINDINGS: In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). CONCLUSIONS: Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity.

Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.

BACKGROUND: The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. METHODS: We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. RESULTS: In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]). CONCLUSIONS: Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.

Mechanisms of autophagy and endoplasmic reticulum stress in the reversal of platinum resistance of epithelial ovarian cancer cells by naringin.

OBJECTIVE: Our previous studies showed that naringin (Nar) can effectively reverse the cisplatin resistance of ovarian cancer cells. This study aims to explore the potential mechanism by which Nar reverses cisplatin resistance in ovarian cancer. METHODS: The proliferative activity of cells was evaluated using CCK8 and cell clone formation assays. Autophagic flux in cells was evaluated via LC3B immunofluorescence and monodansylcadaverine (MDC) staining. The expression levels of autophagy, endoplasmic reticulum (ER) stress, and apoptosis-related proteins were detected via Western blotting. Autophagy and ER stress were regulated using siATG5, siLC3B, rapamycin (Rap), chloroquine (CQ), 4-phenylbutyric acid (4-PBA), and thapsigargin (TG). siATG5 and siLC3B are short interfering RNAs (siRNAs) used to knock down the expression of ATG5 and LC3B genes, respectively. RESULTS: Nar inhibited autophagy in SKOV3/DDP cells by activating the PI3K/AKT/mTOR pathway. And Nar increased the levels of ER stress-related proteins, namely, P-PERK, GRP78, and CHOP, and promoted apoptosis in SKOV3/DDP cells. Moreover, treatment with the inhibitor of ER stress alleviated apoptosis induced by Nar in SKOV3/DDP cells. In addition, compared to cisplatin or naringin alone, the combination of Nar and cisplatin significantly reduced the proliferative activity of SKOV3/DDP cells. And siATG5, siLC3B, CQ or TG pretreatment further inhibited the proliferative activity of SKOV3/DDP cells. Conversely, Rap or 4-PBA pretreatment alleviated the cell proliferation inhibition caused by Nar combined with cisplatin. CONCLUSION: Nar not only inhibited the autophagy in SKOV3/DDP cells by regulating the PI3K/AKT/mTOR signalling pathway, but also promoted apoptosis in SKOV3/DDP cells by targeting ER stress. Nar can reverse the cisplatin resistance in SKOV3/DDP cells through these two mechanisms.

Prenatal exposure to famine and the development of diabetes later in life: an age-period-cohort analysis of the China health and nutrition survey (CHNS) from 1997 to 2015.

PURPOSE: Prenatal exposure to famine has been linked to increased diabetes risk in adulthood. However, one fundamental issue to be addressed is that the reported famine-diabetes relation may be confounded by the age differences between the exposed and non-exposed groups. We aimed to determine the association between prenatal exposure to the Chinese famine of 1959-1962 and risk of diabetes by applying age well-controlled strategies. METHODS: Among 20,535 individuals born in 1955-1966 who participated in the China Health and Nutrition Survey from 1997 to 2015, we constructed age-matched exposed vs. non-exposed groups to investigate the role of prenatal exposure to the Chinese famine of 1959-1962 in relation to diabetes. We also built a hierarchical age-period-cohort (HAPC) model to specifically examine the relation of famine to diabetes risk independent of age. RESULTS: Compared to the age-balanced men in the non-exposed group, the exposed men born in 1961 had a 154% increased risk of diabetes [odds ratio (OR) 2.54 (95% CI 1.07-6.03), P = 0.04). In the HAPC analysis, the predicted probabilities of diabetes peaked in the 1961-birth cohort of men [3.4% (95% CI 2.4%-5.0%)], as compared to the average probability of diabetes (reference) of 1.8% for men overall. Neither analytical strategy revealed any strong relation between famine exposure and diabetes risk in women. CONCLUSION: Among the pre-defined Chinese famine period of 1959-1962, early-life exposure to famine was associated with increased diabetes risk in men but not in women, and these relations were independent of age.

Predicting COVID-19 vaccination intentions: the roles of threat appraisal, coping appraisal, subjective norms, and negative affect.

BACKGROUND: As a new disease, communities possess little natural immunity to COVID-19 and vaccines are considered critical to preventing and reducing the incidence of severe illness. This study, inspired by Protection Motivation Theory (PMT), examines the relationship between citizens' threat appraisal, coping appraisal, subjective norms, negative affect, and their COVID-19 vaccination intentions. METHODS: A sample of 340 citizens from two main cities in Mainland China, Xi'an and Wuxi, was used for data analysis. Structural Equation Modeling (SEM) was employed with latent and observed variables to test hypotheses. Data were analyzed using AMOS 24.0. RESULTS: Several findings extend current understanding. Firstly, our proposed model explains 73% of the variance in vaccination intentions. Secondly, perceived severity only indirectly shapes COVID-19 vaccination intentions through negative affect. Thirdly, negative affect and response costs are negatively related to COVID-19 vaccination intentions. Finally, Perceived probability, subjective norms, response efficacy and self-efficacy are positively related to COVID-19 vaccination intentions; among them, self-efficacy contributes the most, followed by response efficacy and subjective norms, and lastly perceived probability. CONCLUSION: Theoretically, this study increases current understanding about subjective norms and affective responses. We provoke a certain amount of thought about the role of affect response in relation to threat appraisal and vaccination intentions. Specifically, governments must be vigilant that citizens' negative affect, such as fear, may cause vaccine hesitation.

Comparative Analysis of Social Support in Online Health Communities Using a Word Co-Occurrence Network Analysis Approach.

Online health communities (OHCs) have become a major source of social support for people with health problems. Members of OHCs interact online with others facing similar health problems and receive multiple types of social support, including but not limited to informational support, emotional support, and companionship. The aim of this study is to examine the differences in social support communication among people with different types of cancers. A novel approach is developed to better understand the types of social support embedded in OHC posts. Our approach, based on the word co-occurrence network analysis, preserves the semantic structures of the texts. Information extraction from the semantic structures is supported by the interplay of quantitative and qualitative analyses of the network structures. Our analysis shows that significant differences in social support exist across cancer types, and evidence for the differences across diseases in terms of communication preferences and language use is also identified. Overall, this study can establish a new venue for extracting and analyzing information, so as to inform social support for clinical care.

LM-GlycomeAtlas Ver. 2.0: An Integrated Visualization for Lectin Microarray-based Mouse Tissue Glycome Mapping Data with Lectin Histochemistry.

Laser microdissection-assisted lectin microarray has been used to obtain quantitative and qualitative information on glycans on proteins expressed in microscopic regions of formalin-fixed paraffin-embedded tissue sections. For the effective visualization of this "tissue glycome mapping" data, a novel online tool, LM-GlycomeAtlas (https://glycosmos.org/lm_glycomeatlas/index), was launched in the freely available glycoscience portal, the GlyCosmos Portal (https://glycosmos.org). In LM-GlycomeAtlas Version 1.0, nine tissues from normal mice were used to provide one data set of glycomic profiles. Here we introduce an updated version of LM-GlycomeAtlas, which includes more spatial information. We designed it to deposit multiple data sets of glycomic profiles with high-resolution histological images, which included staining images with multiple lectins on the array. The additionally implemented interfaces allow users to display multiple histological images of interest (e.g., diseased and normal mice), thereby facilitating the evaluation of tissue glycomic profiling and glyco-pathological analysis. Using these updated interfaces, 451 glycomic profiling data and 42 histological images obtained from 14 tissues of normal and diseased mice were successfully visualized. By easy integration with other tools for glycoproteomic data and protein glycosylation machinery, LM-GlycomeAtlas will be one of the most valuable open resources that contribute to both glycoscience and proteomics communities.

Polypeptide N-acetylgalactosaminyltransferase 18 retains in endoplasmic reticulum depending on its luminal regions interacting with ER resident UGGT1, PLOD3 and LPCAT1.

Mucin-type O-glycosylation is initiated by the polypeptide: N-acetylgalactosaminyltransferase (ppGalNAc-T) family of enzymes, which consists of 20 members in humans. Among them, unlike other ppGalNAc-Ts located in Golgi apparatus, ppGalNAc-T18 distributes primarily in the endoplasmic reticulum (ER) and non-catalytically regulates ER homeostasis and O-glycosylation. Here, we report the mechanism for ppGalNAc-T18 ER localization and the function of each structural domain of ppGalNAc-T18. By using ppGalNAc-T18 truncation mutants, we revealed that the luminal stem region and catalytic domain of ppGalNAc-T18 are essential for ER localization, whereas the lectin domain and N-glycosylation of ppGalNAc-T18 are not required. In the absence of the luminal region (i.e., stem region, catalytic and lectin domains), the conserved Golgi retention motif RKTK within the cytoplasmic tail combined with the transmembrane domain ensure ER export and Golgi retention, as observed for other Golgi resident ppGalNAc-Ts. Results from coimmunoprecipitation assays showed that the luminal region interacts with ER resident proteins UGGT1, PLOD3 and LPCAT1. Furthermore, flow cytometry analysis showed that the entire luminal region is required for the non-catalytic O-GalNAc glycosylation activity of ppGalNAc-T18. The findings reveal a novel subcellular localization mechanism of ppGalNAc-Ts and provide a foundation to further characterize the function of ppGalNAc-T18 in the ER.

Post-migration well-being of Sub-Saharan Africans in China: a nationwide cross-sectional survey.

PURPOSE: This study aims to understand the quality of life (QOL) among Sub-Saharan African (SSA) migrants and explore the factors that contribute to and shape SSA migrants' QOL and shed light on how post-migration factors affect their QOL in China. METHODS: We conducted a nationwide cross-sectional survey on QOL of SSA migrants in China from August, 2019 to November, 2019. We recruited SSA migrants using a combination of peer-referred online and offline surveys. The WHOQOL-BREF scale assessed the QOL of participants, and depressive symptoms were measured using Center for Epidemiologic Studies-Depression scale. Correlates of well-being including depressive symptoms, migration-related factors, and socio-demographic characteristics were included in hierarchical linear regression models to explore the contributions of these factors on QOL of SSA migrants. RESULTS: This study included 928 eligible SSA migrants. The total score of the WHOQOL-BREF scale was 66.8 ± 14.0. Attitudes of local people toward SSA migrants (ß = 3.1, 95% CI 2.4, 3.0) and satisfaction with their living conditions (ß = 3.6, 95% CI 2.5, 4.7) were positively associated with QOL and explained 12.2% of the variance. Contracting an infectious disease in the past year (ß = - 5.3, 95% CI - 7.6, - 2.9) and depression werenegatively associated with QOL (ß = - 0.7, 95% CI - 0.7, - 0.6) and explained 24.4% of the variance. CONCLUSION: Our study underscores the importance of several key factors that may aid in the improvement of QOL among SSA migrants. Post-migration environmental factors emerged as key correlates of QOL, which builds on previous evidence that the post-migration context should be improved to safeguard the well-being of SSA migrants in China.

Imaging features of sentinel lymph node mapped by multidetector-row computed tomography lymphography in predicting axillary lymph node metastasis.

INTRODUCTION: Accurately assessing axillary lymph node (ALN) status in breast cancer is vital for clinical decision making and prognosis. The purpose of this study was to evaluate the predictive value of sentinel lymph node (SLN) mapped by multidetector-row computed tomography lymphography (MDCT-LG) for ALN metastasis in breast cancer patients. METHODS: 112 patients with breast cancer who underwent preoperative MDCT-LG examination were included in the study. Long-axis diameter, short-axis diameter, ratio of long-/short-axis and cortical thickness were measured. Logistic regression analysis was performed to evaluate independent predictors associated with ALN metastasis. The prediction of ALN metastasis was determined with related variables of SLN using receiver operating characteristic (ROC) curve analysis. RESULTS: Among the 112 cases, 35 (30.8%) cases had ALN metastasis. The cortical thickness in metastatic ALN group was significantly thicker than that in non-metastatic ALN group (4.0 ± 1.2 mm vs. 2.4 ± 0.7 mm, P < 0.001). Multi-logistic regression analysis indicated that cortical thickness of > 3.3 mm (OR 24.53, 95% CI 6.58-91.48, P < 0.001) had higher risk for ALN metastasis. The best sensitivity, specificity, negative predictive value(NPV) and AUC of MDCT-LG for ALN metastasis prediction based on the single variable of cortical thickness were 76.2%, 88.5%, 90.2% and 0.872 (95% CI 0.773-0.939, P < 0.001), respectively. CONCLUSION: ALN status can be predicted using the imaging features of SLN which was mapped on MDCT-LG in breast cancer patients. Besides, it may be helpful to select true negative lymph nodes in patients with early breast cancer, and SLN biopsy can be avoided in clinically and radiographically negative axilla.

A simple bacterial expression system for human ppGalNAc-T and used for the synthesis of O-GalNAc glycosylated interleukin 2.

Mucin-type O-glycosylation (hereafter referred to as O-GalNAc glycosylation) is one of the most abundant glycosylation on proteins. It is initiated by the members of polypeptide N-acetyl-α-galactosaminyltransferases (ppGalNAc-Ts) family. The ppGalNAc-Ts could be used as tool enzymes to modify target proteins including therapeutic glycoprotein drugs with O-GalNAc glycosylation at specific glycosylated sites in vitro. Obtaining a large amount of ppGalNAc-T can greatly increase the yield of therapeutic O-glycoprotein and reduce the culture costs. In this study, we reported a simple Escherichia coli (E. coli) expression system capable of producing human ppGalNAc-Ts. By co-expressing human PDI, we could simply obtain active ppGalNAc-Ts with high efficiency. Using the E. coli expressed ppGalNAc-T2, we site-specifically synthesized O-glycosylated IL-2 at the native glycosylated site Thr23 residue. These results reveal the E. coli system we constructed is suitable to produce active ppGalNAc-Ts and thus has the potential value for basic research and production of therapeutic O-glycoproteins in vitro.

Databases and Bioinformatic Tools for Glycobiology and Glycoproteomics.

Glycosylation plays critical roles in various biological processes and is closely related to diseases. Deciphering the glycocode in diverse cells and tissues offers opportunities to develop new disease biomarkers and more effective recombinant therapeutics. In the past few decades, with the development of glycobiology, glycomics, and glycoproteomics technologies, a large amount of glycoscience data has been generated. Subsequently, a number of glycobiology databases covering glycan structure, the glycosylation sites, the protein scaffolds, and related glycogenes have been developed to store, analyze, and integrate these data. However, these databases and tools are not well known or widely used by the public, including clinicians and other researchers who are not in the field of glycobiology, but are interested in glycoproteins. In this study, the representative databases of glycan structure, glycoprotein, glycan-protein interactions, glycogenes, and the newly developed bioinformatic tools and integrated portal for glycoproteomics are reviewed. We hope this overview could assist readers in searching for information on glycoproteins of interest, and promote further clinical application of glycobiology.

CT imaging features and image evolution characteristics of coronavirus disease 2019. / 2019å† çŠ¶ç— æ¯’ç— çš„è‚ºéƒ¨CTå½±åƒå­¦è¡¨çŽ°åŠç— ç¶æ¼”å˜ç‰¹ç‚¹.

OBJECTIVES: To analyze the imaging features of coronavirus disease 2019 (COVID-19) in different periods, and summarize the characteristics with itsdevelopment. METHODS: We retrospectively analyzed the CT image data of COVID-19 patients diagnosed by nucleic acid test and CT examination in 57 patients in Zhuzhou Central Hospital and Zhuzhou First People's Hospital, and summarized the characteristics of CT imaging and the development of lesions. RESULTS: Most of the cases were characterized by peripheral distribution of lesions. A total of 37 cases (64.91%) were purely peripherally distributed, 16 cases (28.07%) coexisted with peripheral and mid-internal distribution, and 4 cases (7.02%) had simple mid-inner band distribution. In peripherally distributed cases, the long axis of the lesion was mostly parallel to the pleura in 36 cases (63.16%). In the case of inner-middle zone distribution, the long axis of the lesion was mostly parallel and surrounded the bronchial vascular bundle, or distributed along the lung lobules (31.58%). All cases had ground-glass-density foci, 31 cases (54.38%) had fine grid shadows in the lesions, 46 cases (80.70%) had thick vascular shadows in the lesions, and 23 cases (40.35%) showed signs of bronchial inflation. Among the 10 cases of "wrinkling shape" lesions in the first CT examination, except for 1 case without reexamination, the remaining 9 cases had different degrees of absorption in the second CT examination. Among the 26 cases of "wrinkling shape" lesions in the second CT examination, except for 11 cases without reexamination, the other 15 patients had different degrees of absorption in the third CT examination. CONCLUSIONS: The early CT manifestations of COVID-19 are mostly ground-glass-density foci distributed in the subpleural region, some of which are distributed near the bronchial blood vessel bundle and in the central area of the lobule. As the course of the disease progresses, there may be varying degrees of solid components in the lesion. When the lesions show a "wrinkling shape", it is often suggested that the lesions will evolve towards the direction of absorption. These characteristics are of great value in assisting clinical diagnosis and dynamically observing changes undersuch condition.

On-treatment changes of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein are associated with the regression of liver fibrosis in chronic hepatitis B patients on interferon α add-on therapy.

Wisteria floribunda agglutinin-positive Mac-2-binding protein (M2BP) has been identified as a predictor for the response of interferon α (IFN-α) in patients with viral hepatitis. However, whether serum glycosylation isomer of M2BP (M2BPGi) was associated with the regression of liver fibrosis in patients with chronic hepatitis B (CHB) during IFN-α add-on therapy is still unknown. CHB patients were treated with entecavir for 26 weeks followed by entecavir plus pegylated IFN-α for 52 weeks. Liver biopsies were taken at baseline and treatment week 78. The regression of fibrosis was identified according to Ishak standard or Ishak plus Progressive-Indeterminate-Regressive (P-I-R) standard. Serum M2BPGi and liver function tests were measured at baseline and every 26 weeks of treatment. A total of 72 CHB patients were included in the present study. Serum M2BPGi was correlated with fibrosis and necroinflammation both at baseline and week 78. If Ishak standard was used as the reference, only the percent change of M2BPGi at week 52 from week 26 (Δ%M2BPGi26w-52W ) was independently associated with fibrosis regression at treatment week 78, the area under the ROC curve (AUROC) of Δ%M2BPGi26w-52W for predicting fibrosis regression was 0.705. As for Ishak plus P-I-R standard, the AUROC of the predictive model for fibrosis regression (0.896*M2BPGi52W + 0.363*necroinflammation score0w + 2.051*Ishak score0w - 4.489) was 0.888. These data indicated that dynamic changes of serum M2BPGi were associated with fibrosis regression in CHB patients on IFN-α add-on therapy.

Glycomic Signatures of Plasma IgG Improve Preoperative Prediction of the Invasiveness of Small Lung Nodules.

Preoperative assessment of tumor invasiveness is essential to avoid overtreatment for patients with small-sized ground-glass nodules (GGNs) of 10 mm or less in diameter. However, it is difficult to determine the pathological state by computed tomography (CT) examination alone. Aberrant glycans has emerged as a tool to identify novel potential disease biomarkers. In this study, we used a lectin microarray-based strategy to investigate whether glycosylation changes in plasma immunoglobulin G (IgG) provide additional information about the invasiveness of small GGNs before surgery. Two independent cohorts (discovery set, n = 92; test set, n = 210) of GGN patients were used. Five of 45 lectins (Sambucus nigra agglutinin, SNA; Datura stramonium agglutinin, DSA; Galanthus nivalis agglutinin, GNA; Euonymus europaeus lectin, EEL; and Vicia villosa agglutinin, VVA) were identified as independent factors associated with pathological invasiveness of small GGNs (p < 0.01). Receiver-operating characteristic (ROC) curve analysis indicated the combination of these five lectins could significantly improve the accuracy of CT in diagnosing invasive GGNs, with an area under the curve (AUC) of 0.792 (p < 0.001), a sensitivity of 74.6%, and specificity of 74.4%, which was superior to current clinical biomarkers. These results suggest that the multilectin assay based on plasma IgG glycosylation may be a useful in vitro complementary test to enhance preoperative determination of the invasiveness of GGNs and guide surgeons to select proper clinical management to avoid overtreatment.