LINKED CONTENT
This article is linked to Luo et al papers. To view these articles, visit https://doi.org/10.1111/apt.17124 and https://doi.org/10.1111/apt.17159
Human semen, consisting of spermatozoa (sperm) and seminal plasma, represents a special clinical sample type in human body fluid. Protein glycosylation in sperm and seminal plasma plays key roles in ...spermatogenesis, maturation, capacitation, sperm-egg recognition, motility of sperm, and fertilization. In this study, we profiled the most comprehensive O-glycoproteome map of human sperm and seminal plasma using our recently presented Glycoproteomics based on Two Complementary Fragmentation Methods (GlycoTCFM). We showed that sperm and seminal plasma contain many novel and distinctive O-glycoproteins, which are mostly located in the extracellular region (seminal plasma) and sperm membrane, enriched in the biological processes of cell adhesion and angiogenesis, and mainly involved in multiple biological functions including extracellular matrix structural constituents and binding. Based on GlycoTCFM, we created a comprehensive human sperm and seminal plasma O-glycoprotein database that contains 371 intact O-glycopeptides and 202 O-glycosites from 68 O-glycoproteins. Interestingly, 105 manually confirmed O-glycosites from 25 O-glycoproteins were reported for the first time, and they were mainly modified by core 1 O-glycans. We also found that three highly abundant, highly complex, and highly O-glycosylated proteins (semenogelin-1, semenogelin-2, and equatorin) may play important roles in sperm or seminal plasma composition and function. These data deepen our knowledge about O-glycosylation in sperm and seminal plasma and lay the foundation for the functional study of O-glycoproteins in male infertility.
•Combine three different semantic distance algorithms (WordNet, Google Distance, and ESA) with three re-ranking algorithms (MMR, xQuAD, and Score Difference algorithms) for image result ...diversification.•Data: 269,648 images selected from NUS-WIDE datasets with manually annotated subtopics.•Affirm the effectiveness of this combination of nine algorithms for improving result diversification in image retrieval under different indicators.•The WordNet based semantic distance combined with the Score Difference (WordNet-DivScore) algorithm outperformed the other algorithms.
User requirements for result diversification in image retrieval have been increasing with the explosion of image resources. Result diversification requires that image retrieval systems are made capable of handling semantic gaps between image visual features and semantic concepts, and providing both relevant and diversified image results. Context information, such as captions, descriptions, and tags, provides opportunities for image retrieval systems to improve their result diversification. This study explores a mechanism for improving result diversification using the semantic distance of image social tags. We design and compare nine strategies that combine three different semantic distance algorithms (WordNet, Google Distance, and Explicit Semantic Analysis) with three re-ranking algorithms (MMR, xQuAD, and Score Difference) for result diversification. In order to better prove the effectiveness of our strategy of applying semantic information, we also make use of visual features of images for result diversification experiment and make comparison. Our data for experimentation were extracted from 269,648 images selected from the NUS-WIDE datasets with manually annotated subtopics. Experimental results affirm the effectiveness of applying semantic information for improving result diversification in image retrieval. In particular, WordNet-based semantic distance combined with the Score Difference (WordNet-DivScore) outperformed other strategies in diversifying image retrieval results.
We performed a prospective study to explore a diagnosis and treatment protocol of transient intussusception in children (TIC). Totally, 143 children with intussusception who met the inclusion ...criteria were firstly divided into intussusception involving only the small bowel and intussusception involving the colon group. And in each group, they were further divided into short-segment (≤ 3.0 cm) and long-segment (> 3.0 cm) groups according to the length of intussusception. After a period of conservative treatment, the incidence of TIC, the incidence of surgery, and recurrence were collected and analyzed. Finally, we found that the incidence of TIC in the short-segment group of small bowel intussusception (96.29%) was significantly higher than that in other groups (
P
≤ 0.001). Besides, the incidence of surgery and recurrence in this group was relatively low too. Therefore, we summarized the inclusion criteria and treatments to the short-segment group of small bowel intussusception as the suggested protocol to TIC.
Conclusion
: For cases of small bowel intussusception with no identified pathologic lead point, a short duration of symptoms, a length of ≤ 3.0 cm, a relatively abundant vascular flow signal, and a stable general condition, the spontaneous reduction could be expected and a period of conservative treatment with careful monitoring is recommended.
What is Known:
• The phenomenon of spontaneous reduction in intussusception (transient intussusception) among pediatric patients has been widely reported.
• To distinguish the transient intussusception from the other types is important for the transient ones only need conservative treatment rather than enema reduction or surgery.
What is New:
• This is the first prospective study to explore a diagnosis and treatment protocol of transient intussusception in children.
• Short-segment small bowel intussusceptions have a higher rate (96.29%) to get spontaneous reduction than the other types of intussusception.
Summary
Background
Hepatitis B virus (HBV) infection is a serious global health burden. TRIM26 has been reported to affect hepatitis C virus replication.
Aims
To manifest the role of TRIM26 on HBV ...replication and explore if there are single‐nucleotide polymorphisms (SNPs) in TRIM26 associated with response to pegylated interferon‐alpha (PegIFNα) treatment in patients with chronic hepatitis B (CHB).
Methods
We investigated the effect and mechanism of TRIM26 on HBV replication in vitro. The association between SNPs in TRIM26 and PegIFNα treatment response was evaluated in two independent cohorts including 238 and 707 patients with HBeAg‐positive CHB.
Results
Knockdown of TRIM26 increased, while overexpression of TRIM26 inhibited, HBV replication. Co‐immunoprecipitation assays and immunofluorescence showed that TRIM26 interacted and co‐localised with HBx. Co‐transfection of HBx‐HIS and TRIM26‐FLAG plasmids in Huh7 cells showed that TRIM26 inhibited the expression of HBx. Furthermore, TRIM26 inhibited HBV replication by mediating HBx ubiquitination degradation, and TRIM26 SPRY domain was responsible for the interaction and degradation of HBx. Besides, IFN increased TRIM26 expression. TRIM26 rs116806878 was associated with response to PegIFNα in two CHB cohorts. Moreover, a polygenic score integrating TRIM26 rs116806878, STAT4 rs7574865 and CFB rs12614 (previously reported to be associated with response to PegIFNα) was related to response to PegIFNα in CHB.
Conclusions
TRIM26 inhibits HBV replication; IFN promotes TRIM26 expression. TRIM26 exerts an inhibitory effect on HBx by promoting ubiquitin‐mediated degradation of HBx. Furthermore, TRIM26 rs116806878 is a potential predictive biomarker of response to PegIFNα in patients with CHB.
“TRIM26 inhibits HBV replication by promoting HBx degradation” and “TRIM26 rs116806878 predicts PegIFNα treatment response of HBeAg‐positive CHB patients".
The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) characterized by 30 mutations in its spike protein, has rapidly spread worldwide since November 2021, significantly ...exacerbating the ongoing COVID‐19 pandemic. In order to investigate the relationship between these mutations and the variant's high transmissibility, we conducted a systematic analysis of the mutational effect on spike–angiotensin‐converting enzyme‐2 (ACE2) interactions and explored the structural/energy correlation of key mutations, utilizing a reliable coarse‐grained model. Our study extended beyond the receptor‐binding domain (RBD) of spike trimer through comprehensive modeling of the full‐length spike trimer rather than just the RBD. Our free‐energy calculation revealed that the enhanced binding affinity between the spike protein and the ACE2 receptor is correlated with the increased structural stability of the isolated spike protein, thus explaining the omicron variant's heightened transmissibility. The conclusion was supported by our experimental analyses involving the expression and purification of the full‐length spike trimer. Furthermore, the energy decomposition analysis established those electrostatic interactions make major contributions to this effect. We categorized the mutations into four groups and established an analytical framework that can be employed in studying future mutations. Additionally, our calculations rationalized the reduced affinity of the omicron variant towards most available therapeutic neutralizing antibodies, when compared with the wild type. By providing concrete experimental data and offering a solid explanation, this study contributes to a better understanding of the relationship between theories and observations and lays the foundation for future investigations.
Background and Objective
Teeth overeruption is a problem of clinical significance, but the underlying mechanism how changes in external occlusal force convert to the periodontium remodeling signals ...has been a largely under explored domain. And recently, periodontal ligament‐associated protein‐1 (PLAP‐1)/asporin was found to play a pivotal role in maintaining periodontal homeostasis. The aim of this study was to explore the function of PLAP‐1 in the periodontally hypofunctional tissue turnover.
Methods
After extracting left maxillary molars in mice, the left and right mandibular molars were distributed into hypofunction group (HG) and control group (CG), respectively. Mice were sacrificed for radiographic, histological, and molecular biological analyses after 1, 4 and 12 weeks. In vitro, dynamic compression was applied using Flexcell FX‐5000 Compression System to simulate intermittent occlusal force. The expression of PLAP1 in loaded and unloaded human periodontal ligament cells (hPDLCs) was compared, and its molecular biological effects were further explored by small interfering RNA (siRNA) targeting PLAP1.
Results
In vivo, fiber disorder in periodontal ligament (PDL), bone apposition at furcation regions, and bone resorption in alveolar bone were illustrated in the HG compared with the CG. In addition, PLAP‐1 positive area decreased significantly in PDL following occlusal unloading. In vitro, the loss of compressive loading relatively downregulated PLAP1 expression, which was essential to promote collagen I but inhibit osterix and osteocalcin expression in hPDLCs.
Conclusions
PLAP‐1 presumably plays a pivotal role in occlusal force‐regulated periodontal homeostasis by facilitating collagen fiber synthesis in hPDLCs and suppressing excessive osteoblast differentiation, further preventing teeth from overeruption. Further evidence in PLAP‐1 conditional knockout mice is needed.
Abstract
Protein post-translational modifications (PTMs) play an important role in different cellular processes. In view of the importance of PTMs in cellular functions and the massive data ...accumulated by the rapid development of mass spectrometry (MS)-based proteomics, this paper presents an update of dbPTM with over 2 777 000 PTM substrate sites obtained from existing databases and manual curation of literature, of which more than 2 235 000 entries are experimentally verified. This update has manually curated over 42 new modification types that were not included in the previous version. Due to the increasing number of studies on the mechanism of PTMs in the past few years, a great deal of upstream regulatory proteins of PTM substrate sites have been revealed. The updated dbPTM thus collates regulatory information from databases and literature, and merges them into a protein-protein interaction network. To enhance the understanding of the association between PTMs and molecular functions/cellular processes, the functional annotations of PTMs are curated and integrated into the database. In addition, the existing PTM-related resources, including annotation databases and prediction tools are also renewed. Overall, in this update, we would like to provide users with the most abundant data and comprehensive annotations on PTMs of proteins. The updated dbPTM is now freely accessible at https://awi.cuhk.edu.cn/dbPTM/.
Numerous treatment modalities have been attempted for masticatory muscle pain in patients with temporomandibular disorders (TMD). To compare the treatment efficacy of more than 2 competing ...treatments, a network meta-analysis (NMA) was conducted.
This study was reported with reference to the extended Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting of systematic reviews incorporating network meta-analyses. Medline via Pubmed, Embase via OVID, and Cochrane Library Central were searched (up to February 11, 2019). Axis I protocol of Diagnostic Criteria or Research Diagnostic Criteria for Temporomandibular Disorders (DC/TMD, RDC/TMD) were chosen as diagnostic standards. The PICOS (Problem/patient, Intervention, Comparison, Outcome, Study design) method was used to screen trials under eligibility criteria. And the NMA was performed with mvmeta commands in Stata (StataCorp, Tex).
Of 766 studies searched, 12 randomized clinical trials (RCTs) were finally included. Nineteen different therapies were found and further categorized into 9 treatment modalities. The general heterogeneity was not found among included trials. But predictive intervals (PrIs) were conspicuously wider than confidential intervals (CIs) of all pairwise comparisons, indicating that heterogeneity may exist between studies. Complementary therapy showed the greatest probability (42.7%) to be the best intervention. It also had the highest mean rank (2.3) in the rankogram and the biggest value of surface under the cumulative ranking (SUCRA, 84.1%).
Based on the limited evidence of available trials, complementary therapy seemed to be slightly more effective than remaining treatment modalities for pain reduction in TMD patients with masticatory muscle pain. High-quality randomized controlled trials are expected to validate the findings.
Abstract
More than 250 million people in the world are chronically infected with hepatitis B virus (HBV), which causes serious complications. Host genetic susceptibility is essential for chronic ...hepatitis B (CHB), and our previous genome-wide association study identified a single-nucleotide polymorphism (SNP), rs1883832, in the 5′ untranslated region of CD40 predisposing to chronic HBV infection, but the underlying mechanism remains undefined. This study aimed to investigate whether rs1883832 was the real functional SNP (fSNP) of CD40 and how it modulated HBV clearance in hepatocytes. We determined the fSNP of CD40 and its regulatory protein(s) using luciferase reporter assays, electrophoretic mobility shift assay, flanking restriction enhanced pulldown and chromatin immunoprecipitation. The potential anti-HBV activity of CD40 and its downstream molecule BST2 was assessed in HBV-transfected and HBV-infected hepatoma cells and HBV-infected primary human hepatocytes. Moreover, the mechanism of CD40 was investigated by mRNA sequencing, quantitative real-time polymerase chain reaction, immunofluorescence and western blot. We revealed rs1883832 as the true fSNP of CD40 and identified ANXA2 as a negative regulatory protein that preferentially bound to the risk allele T of rs1883832 and hence reduced CD40 expression. Furthermore, CD40 suppressed HBV replication and transcription in hepatocytes via activating the JAK–STAT pathway. BST2 was identified to be the key IFN-stimulated gene regulated by CD40 after activating JAK–STAT pathway. Inhibition of JAK/STAT/BST2 axis attenuated CD40-induced antiviral effect. In conclusion, a functional variant of CD40 modulates HBV clearance via regulation of the ANXA2/CD40/BST2 axis, which may shed new light on HBV personalized therapy.
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