RNALocate v3.0: Advancing the Repository of RNA Subcellular Localization with Dynamic Analysis and Prediction.

Subcellular localization of RNA is a crucial mechanism for regulating diverse biological processes within cells. Dynamic RNA subcellular localizations are essential for maintaining cellular homeostasis; however, their distribution and changes during development and differentiation remain largely unexplored. To elucidate the dynamic patterns of RNA distribution within cells, we have upgraded RNALocate to version 3.0, a repository for RNA-subcellular localization (http://www.rnalocate.org/ or http://www.rna-society.org/rnalocate/). RNALocate v3.0 incorporates and analyzes RNA subcellular localization sequencing data from over 850 samples, with a specific focus on the dynamic changes in subcellular localizations under various conditions. The species coverage has also been expanded to encompass mammals, non-mammals, plants and microbes. Additionally, we provide an integrated prediction algorithm for the subcellular localization of seven RNA types across eleven subcellular compartments, utilizing convolutional neural networks (CNNs) and transformer models. Overall, RNALocate v3.0 contains a total of 1 844 013 RNA-localization entries covering 26 RNA types, 242 species and 177 subcellular localizations. It serves as a comprehensive and readily accessible data resource for RNA-subcellular localization, facilitating the elucidation of cellular function and disease pathogenesis.

Outstanding Energy-Storage Density Together with Efficiency of above 90% via Local Structure Design.

Dielectric ceramic capacitors with high recoverable energy density (Wrec) and efficiency (η) are of great significance in advanced electronic devices. However, it remains a challenge to achieve high Wrec and η parameters simultaneously. Herein, based on density functional theory calculations and local structure analysis, the feasibility of developing the aforementioned capacitors is demonstrated by considering Bi0.25Na0.25Ba0.5TiO3 (BNT-50BT) as a matrix material with large local polarization and structural distortion. Remarkable Wrec and η of 16.21 J/cm3 and 90.5% have been achieved in Bi0.25Na0.25Ba0.5Ti0.92Hf0.08O3 via simple chemical modification, which is the highest Wrec value among reported bulk ceramics with η greater than 90%. The examination results of local structures at lattice and atomic scales indicate that the disorderly polarization distribution and small nanoregion (∼3 nm) lead to low hysteresis and high efficiency. In turn, the drastic increase in local polarization activated via the ultrahigh electric field (80 kV/mm) leads to large polarization and superior energy storage density. Therefore, this study emphasizes that chemical design should be established on a clear understanding of the performance-related local structure to enable a targeted regulation of high-performance systems.

Unleashed Remarkable Energy Storage Performance in Bi0.5K0.5TiO3-based Relaxor Ferroelectrics by Local Structural Fluctuation.

Dielectric capacitors harvest energy through an electrostatic process, which enables an ultrafast charging-discharging rate and ultrahigh power density. However, achieving high energy density (Wrec) and efficiency (η) simultaneously, especially when preserving them across a wide frequency/temperature range or cycling numbers, remains challenging. In this work, by especially introducing NaTaO3 into the representative ferroelectric relaxor of Bi0.5K0.5TiO3-Bi0.5Na0.5TiO3 and leveraging the mismatch between B-site atoms, we proposed a method of enhancing local structural fluctuation to refine the polar configuration and to effectively improve its overall energy-storage performances. As a consequence, the ceramic exhibits an ultrahigh Wrec of 15.0 J/cm3 and high η up to 80%, along with a very wide frequency stability of 10 - 200 Hz and extensive cycling number up to 108. In-depth local structure and chemical environment investigations, consisting of atom-scale electron microscopy, neutron total scattering, and solid-state nuclear magnetic resonance, reveal that the randomly distributed A/B-site atom pairs emerge in the system, leading to the evident local structural fluctuations and concomitant polymorphic polar nanodomains. These key ingredients contribute to the large polarization, minimal hysteresis, and high breakdown strength, thereby promoting energy-storage performances. This work opens a new path for designing high-performance dielectric capacitors via manipulating local structural fluctuations.

The effect of Helicobacter pylori eradication on prognosis of postoperative early gastric cancer: a multicenter study.

OBJECTIVE: To investigate the effect of Helicobacter pylori (H. pylori) eradication on the prognosis of postoperative early gastric cancer (EGC). METHODS: This is a retrospective study based on data from 6 hospitals. We identified 429 patients with EGC who underwent curative gastrectomy from January 2010 to December 2016. All of the patients were tested for H. pylori. Patients were divided into two groups, the successful H. pylori eradication group (group A, 268 patients) and the non-H. pylori eradication group (group B, 161 patients), for calculating the disease-free survival (DFS) and overall survival (OS) of each group. RESULT: Positive node metastasis (hazard ratio (HR), 3.13; 95% confidence interval (CI), 1.84-5.32; P < 0.001), undifferentiated type (HR, 2.54; 95% CI, 1.51-4.28; P < 0.001), and non-H. pylori eradication (HR, 1.73; 95% CI, 1.08-2.77; P = 0.023) were statistically significantly independent risk factors of recurrence. Patient's age ≥60 years old (HR, 3.32; 95% CI, 2.00-5.53; P < 0.001), positive node metastasis (HR, 3.71; 95% CI, 2.25-6.12; P < 0.001), undifferentiated type (HR, 3.06; 95% CI, 1.79-5.23; P < 0.001), and non-H. pylori eradication (HR, 1.83; 95% CI, 1.11-3.02; P = 0.018) were statistically significantly independent risk factors of overall survival. CONCLUSION: H. pylori eradication treatment could prevent the recurrence of postoperative EGC to prolong the overall survival of patients with EGC.

MiR-9 Regulates the Expression of BACE1 in Dementia Induced by Chronic Brain Hypoperfusion in Rats.

BACKGROUND/AIMS: MicroRNA-9 (miR-9) plays important roles in nervous system diseases such as glioblastoma and neurodegenerative disorders. However, how miR-9 contributes to dementia requires further study. In this study, we evaluated the role of miR-9 in dementia and the molecular mechanisms underlying its effects. METHODS: A rat model of dementia was created by occlusion of the bilateral common carotid artery (2VO) for 8 weeks. Learning and memory were assessed using the Morris Water Maze (MWM). MicroRNA expression profiling was performed according to a protocol provided by LC Sciences, and quantitative real-time PCR (qRT-PCR) was used to detect the level of miR-9. Transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining were used to assess pathological changes in brain tissue. Western blot and immunofluorescence were employed to detect the expression of ß-site APP cleaving enzyme 1 (BACE1) and c-AMP response element-binding protein (CREB). RESULTS: Learning and memory were significantly impaired in 2VO rats, and these changes were accompanied by neuronal loss and glial activation in brain tissues. miR-9 was greatly upregulated in both the hippocampus and cortex of rats following 2VO. Knockdown of endogenous miR-9 via lentiviral vector-mediated delivery of its antisense molecule (lenti-pre-AMO-miR-9) reduced the vulnerability to dementia, reversed the increase in BACE1 expression, and ameliorated the reduction in CREB expression triggered by 2VO. BACE1 protein levels were significantly increased, but CREB protein levels were significantly decreased in the presence of miR-9 in cultured neonatal rat neurons (NRNs). AMO-miR-9 rescued the upregulation of BACE1 and downregulation of CREB elicited by miR-9 in rats. Dual luciferase assay experiments showed that overexpression of miR-9 inhibited the expression of CREB by targeting its 3'UTR domain. CREB protein was downregulated by miR-9 overexpression which was reversed by miR-9 inhibition in cultured NRNs. TEM imaging showed that miR-9 caused damage to NRNs, which was reversed by addition of AMO-miR-9. CONCLUSION: We conclude that miR-9 plays an important role in regulating the process of dementia induced by 2VO in rats by increasing BACE1 expression via downregulation of CREB.

Study of the NLRP3 inflammasome component genes and downstream cytokines in patients with type 2 diabetes mellitus with carotid atherosclerosis.

BACKGROUND: A role for the NLRP3 inflammasome has been reported in various diseases, such as diabetes mellitus, atherosclerosis (AS), nephropathy, rheumatism, and others, although limited information is available concerning the role of the NLRP3 inflammasome, interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in patients with type 2 diabetes mellitus (T2DM) and carotid atherosclerosis (CAS). Therefore, this cross-sectional study investigated these inflammatory components in patients with T2DM complicated with carotid atherosclerosis (T2DM + CAS). METHODS: A total of 107 inpatients or outpatients were included,including 81 T2DM + CAS patients and 26 T2DM patients. Patients with T2DM or T2DM + CAS were recruited to compare the expression levels of NLRP3 pathway genes (NLRP3, ASC and caspase-1 mRNA) and the serum IL-1ß and IL-18 concentrations. In the T2DM + CAS group, patients with thickened intima media thickness (IMT) and those with plaques were compared, and the correlation of the 5 variables with Crouse scores were analyzed. RESULTS: The expression of NLRP3 pathway genes except caspase-1 was significantly higher in patients with T2DM and CAS compared to T2DM patients. Serum IL-1ß and IL-18 concentrations shows no difference between the T2DM + CAS and T2DM group. In the T2DM + CAS group, the expression levels of the three inflammasome genes and IL-18 were increased in patients with thickened IMT compared to those with the plaque. All of the above factors negatively correlated with Crouse scores. CONCLUSION: NLRP3 inflammasome pathway activity is significantly increased in patients with AS and T2DM at the early stage of plaque formation.

Interferon-α and cyclooxygenase-2 inhibitor cooperatively mediates TRAIL-induced apoptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Interferon-alpha (IFN-α) has recently been recognized to harbor therapeutic potential in the prevention and treatment of HCC, but it remains controversial as to whether IFN-α exerts direct cytotoxicity against HCC. Cyclooxygenase-2 (COX-2) is overexpressed in HCC and is considered to play a role in hepatocarcinogenesis. Therefore, we aimed to elucidate the combined effect of a COX-2 inhibitor, celecoxib, and IFN-α on in vitro growth suppression of HCC using the hepatoma cell line HLCZ01 and the in vivo nude mouse xenotransplantation model using HLCZ01 cells. Treatment with celecoxib and IFN-α synergistically inhibited cell proliferation in a dose- and time-dependent manner. Apoptosis was identified by 4׳,6-diamidino-2-phenylindole dihydrochloride and fluorescent staining. IFN-α upregulated the expression of TRAIL, while celecoxib increased the expression of TRAIL receptors. The combined regimen with celecoxib and IFN-α reduced the growth of xenotransplanted HCCs in nude mice. The regulation of IFN-α- and COX-2 inhibitor-induced cell death is impaired in a subset of TRAIL-resistant cells. The molecular mechanisms of HCC cells resistant to TRAIL-induced apoptosis were explored using molecular biological and immunological methods. Interferon-α and the COX-2 inhibitor celecoxib synergistically increased TRAIL-induced apoptosis in hepatocellular carcinoma. These data suggest that IFN-α and celecoxib may offer a novel role with important implications in designing new therapeutics for TRAIL-resistant tumors.

Alteration in amyloid ß42, phosphorylated tau protein, interleukin 6, and acetylcholine during diabetes-accelerated memory dysfunction in diabetic rats: correlation of amyloid ß42 with changes in glucose metabolism.

BACKGROUND: Diabetes accelerates memory dysfunction in a continuous, slowly pathological process. Studies suggest that the time course of certain biomarkers can characterize the pathological course of the disease to provide information for early intervention. Thus, there is an urgent need for validated biomarkers to characterize the cognitive impairment induced by DM. We aimed to detect changes in cerebrospinal fluid biomarkers such as amyloid ß42, phosphorylated tau protein, interleukin 6, and acetylcholine in diabetic rats over time, and to analyse the relationship between diabetes and cognitive impairment. METHODS: Rats were injected once intraperitoneally with 1% of streptozotocin to establish a diabetic model. Index changes were investigated longitudinally and all were measured at the end of the experiment at day 75. Aß42, P-tau, IL-6, and ACh levels in CSF, insulin levels in plasma, and Aß42 levels in plasma and brain tissue were measured by ELISA. RESULTS: Compared with control, the diabetic model showed ACh in CSF to be decreased by day 15, continuing lower out to day 75. Aß42 changes in brain and blood showed the same trends but exhibited minima at different time points: day 30 in CSF and day 15 in plasma. After the minimum, Aß42 in cerebrospinal fluid rose and levelled off lower than in the control group, whereas Aß42 in plasma rose and went above the controls at day 30, slowly trending upwards for the remainder of the experiment. P-tau protein in CSF in diabetic rats showed an increasing trend, becoming significantly different from the controls at day 60 and day 75. Aß42 in CSF was strongly negatively correlated with blood glucose at day 15 and was negatively correlated with insulin in serum, particularly at day 45. CONCLUSION: Our longitudinal research model suggest that changes in the measured biomarkers appear before learning and memory impairments do. Aß42 and ACh in the diabetes model group clearly changed from day 0 to day 45, and then P-tau and IL-6 varied significantly from day 45 to day 75. The reduced ACh levels observed possibly correlated with the factors common to changes in Aß42, P-tau, and IL-6.

U6 is not a suitable endogenous control for the quantification of circulating microRNAs.

Recently, microRNAs have been detected in serum and plasma, and circulating microRNA (miRNA) profiles have now been associated with many diseases such as cancers and heart disease, as well as altered physiological states. Because of their stability and disease resistance, circulation miRNAs appear to be an ideal material for biomarkers of diseases and physiological states in blood. However, the lack of a suitable internal reference gene (internal reference miRNA) has hampered research and application of circulating miRNAs. Currently, U6 and miR-16 are the most common endogenous controls in the research of miRNAs in tissues and cells. We performed microarray-based serum miRNA profiling on the serum of 20 nasopharyngeal carcinoma patients and 20 controls to detect the expressions of U6 and miRNAs. Profiling was followed by real-time quantitative Polymerase Chain Reaction (qPCR) in 80 patients (20 each with gastric cancer, nasopharyngeal carcinoma, colorectal cancer, and breast cancer) and 30 non-cancerous controls. qPCR was also performed to detect miRNAs in serum with repeated freezing and thawing. The results of microarray showed that with the exception of U6, Ct values of miR-16, miR-24, miR-142-3p, miR-19b and miR-192 in serum samples of nasopharyngeal carcinoma were greater than control samples. The results of 110 cases showed large fluctuations in U6 expression. The difference between the greatest and the least levels of expression was 3.29 for delta Ct values, and 1.23 for miR-16. The expressions of U6, miR-16 and miR-24 in serum subjected to different freeze-thaw cycles showed that U6 expression gradually decreased after 1, 2, and 4 cycles of freezing and thawing, while the expression of miR-16 and miR-24 remained relatively stable. Collectively, our results suggested that U6 is unsuitable as an internal reference gene in the research of circulating miRNAs.

EBV-positive glycoproteins associated with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is closely related to Epstein-Barr virus (EBV) infection, and glycosylation of proteins is associated with precancerous lesions and carcinogenesis of NPC, and viral glycoproteins mediates the fusion of viruses with B cells or epithelial cells in the infection stage, promoting the conversion of normal epithelial cells into cancer cells. In the process of occurrence and development of NPC, various glycoproteins in the body promote or inhibit the proliferation, invasion, metastasis, and drug resistance of tumor cells, such as the tumor inhibitory effect of NGX6 and inhibin B (INHBB); the cancer-promoting effect of tenascin-C (TNC), fibronectin 1 (FN1), insulin-like growth factor binding protein-3 (IGFBP3), serglycin, and its core protein; and some effects of glycosylation of immune proteins on immunotherapy in NPC. This article provides an overview of the research progress on the interaction of glycoproteins associated with EBV infection with the occurrence and development of NPC.

The advancement of siRNA-based nanomedicine for tumor therapy.

Small interfering RNA (siRNA) has been proved to be able to effectively down-regulate gene expression through the RNAi mechanism. Thus, siRNA-based drugs have become one of the hottest research directions due to their high efficiency and specificity. However, challenges such as instability, off-target effects and immune activation hinder their clinical application. This review explores the mechanisms of siRNA and the challenges in siRNA-based tumor therapy. It highlights the use of various nanomaterials - including lipid nanoparticles, polymeric nanoparticles and inorganic nanoparticles - as carriers for siRNA delivery in different therapeutic modalities. The application strategies of siRNA-based nanomedicine in chemotherapy, phototherapy and immunotherapy are discussed in detail, along with recent clinical advancements. Aiming to provide insights for future research and therapeutic approaches.

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AR expression-independent XRCC3 mediates DNA damage-induced p53/Bax signaling pathway activation against prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) resistance is closely associated with altered AR status. Aberrant AR expression is critical for the induction of ADT resistance, necessitating the identification of an anti-PCa target independent of AR expression. METHODS: Transcriptomic data and clinical information of PRAD were obtained from TCGA database. Genes with PCa-related and AR expression-independent were screened by bioinformatics, and characterized by PPI and GO functional enrichment analyses. Candidate genes were locked by co-expression correlation and disease-free survival (DFS) analyses. A prognostic gene set was established using LASSO Cox regression algorithm. Cox proportional risk regression was performed to identify a key prognostic gene. Expression of the target protein in PCa tissues was verified by The Human Protein Atlas database. In vitro validation of cellular function and molecular mechanism by knockdown and overexpression of the target gene. RESULTS: Two AR expression-independent genes (SLC43A1 and XRCC3) were available for the optimal prognostic model. This gene set effectively predicted PRAD patients' DFS at 1-, 3- and 5-year, where XRCC3 and tumor (T) stage were independent risk factors. XRCC3 was higher expressed in PRAD patients with T3-T4 stages and accompanied by poorer DFS. IHC staining also validated its higher expression in high-risk PCa tissues. In vitro experiments demonstrated that silencing XRCC3 significantly inhibited 22Rv1 and DU145 cell proliferation, migration and invasion, while promoted apoptosis. Further, silencing XRCC3 promoted DNA damage-induced p53/Bax signaling pathway activation, which was absent with overexpression. CONCLUSION: Silencing XRCC3 exerts anti-PCa effects by promoting DNA damage-induced p53/Bax signaling pathway activation in an AR expression-independent manner.

RIscoper 2.0: A deep learning tool to extract RNA biomedical relation sentences from literature.

RNA plays an extensive role in a multi-dimensional regulatory system, and its biomedical relationships are scattered across numerous biological studies. However, text mining works dedicated to the extraction of RNA biomedical relations remain limited. In this study, we established a comprehensive and reliable corpus of RNA biomedical relations, recruiting over 30,000 sentences manually curated from more than 15,000 biomedical literature. We also updated RIscoper 2.0, a BERT-based deep learning tool to extract RNA biomedical relation sentences from literature. Benefiting from approximately 100,000 annotated named entities, we integrated the text classification and named entity recognition tasks in this tool. Additionally, RIscoper 2.0 outperformed the original tool in both tasks and can discover new RNA biomedical relations. Additionally, we provided a user-friendly online search tool that enables rapid scanning of RNA biomedical relationships using local and online resources. Both the online tools and data resources of RIscoper 2.0 are available at http://www.rnainter.org/riscoper.

Biomimetic graphene oxide quantum dots nanoparticles targeted photothermal-chemotherapy for gastric cancer.

Direct use of chemotherapy drugs in the treatment of gastric cancer often leads to systemic side effects and unsatisfied therapeutic efficacy due to the lack of tumour-targeting ability. The excellent properties of nanoparticles make them good tools to provide more options for the targeted delivery of chemotherapeutic drugs. Herein, we developed a novel nanomedicine (GOQD-ICG-CS-6@HM nanoparticles, GIC@HM NPs), which employed graphene oxide quantum dots (GOQDs) to co-load photosensitizer indocyanine green (ICG) and chemotherapeutic drug gamabufotalin (CS-6) as the core and wrapped with the hybrid membrane (erythrocyte membrane and gastric cancer cell membrane, HM) on its surface. This nanomedicine possesses the functions of photothermal therapy and chemotherapy, making it a good choice for the treatment of gastric cancer. The results showed that the bionic-coated hybrid membrane not only improves the biocompatibility of the nanomedicine, and prolong its circulating half-life, but also delivers the drug to the tumour site precisely and improves the efficiency of drug utilisation. In vitro and in vivo studies further showed that GIC@HM NPs exhibited combinational effects on tumour therapy while displaying no obvious side effects on normal tissue. To sum up, the newly developed GIC@HM NPs provide a safer, more efficient, and more precise method for gastric cancer treatment.

Integrated glycomics strategy for galactosylated-N-glycans recognized by Bandeiraea Simplicifolia Lectin I in salivary proteins associated with lung cancer.

PURPOSE: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. Saliva is an important source for discovering biomarkers and contains an abundance of biological information. The purpose of this study was to determine whether galactosylation levels of salivary proteins are associated with LC. EXPERIMENTAL DESIGN: First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays. Pooled samples from each group were subsequently validated by the lectin blotting technique. Finally, the N-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from pooled samples for each group were analyzed by MALDI-TOF/TOF-MS. RESULTS: The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with LC compared with BPD and HV. Receiver operating characteristic (ROC) analysis indicated that the levels of salivary glycopattern recognized by BS-I could discriminate lung disease (BPD, ADC, SCC, and SCLC) and HV with an AUC of 0.700 (95% CI: 0.589-0.812), and discriminate LC and BPD with an AUC of 0.860 (95% CI: 0.763-0.956). Also, the proportion of galactosylated N-glycans in ADC (38.4%), SCC (43.1%), and SCLC (39.5%) increased compared to HV (30.1%) and BPD (33.7%), and two galactosylated N-glycan peaks (m/z 1828.683, 2418.853) could be identified only in the LC groups (ADC, SCC, and SCLC). CONCLUSIONS AND CLINICAL RELEVANCE: These findings could provide crucial information on galactosylated N-linked glycans associated with LC and facilitate the study of LC biomarkers based on precise alterations of galactosylated N-glycans in saliva.

Reduction of CAII Expression in Gastric Cancer: Correlation with Invasion and Metastasis.

OBJECTIVE: Human carbonic anhydrases II (CAII) gene plays an important role in different cancer. However, its relevance to gastric cancer (GC) remains unclear. In the present study, we aimed to investigate the expression of CAII in GC and explore its correlation with some clinicopathologic characteristics of GC. METHODS: The expression of CAII in 20 specimens of normal gastric mucosa, 38 specimens of intraepithelial neoplasia and 112 specimens of gastric carcinoma were detected by immunohistochemical techniques. Survival in GC with CAII expression was studied. RESULTS: The positive rate of CAII protein in normal gastric mucosa was significantly higher than that in intraepithelial neoplasia and gastric carcinoma (100% vs. 63.16% and 28.57%, P<0.001). The positive rate of CAII protein was significantly higher in gastric carcinoma at early stages than that at advanced stages (70.0% vs. 19.57%, P<0.001). The positive rate of CAII protein was significantly lower in gastric carcinoma with lymph node metastases than that without lymph node metastases (10.81% vs. 37.33%, P<0.05). Furthermore, the positive rate of CAII protein was significantly lower in poorly-differentiated gastric carcinoma than in moderately- or well-differentiated gastric carcinoma (15.94% vs. 31.03% or 60.00%, P<0.05). Moreover, CAII expression was not related with sex, age and tumor size. The patients with CAII-positive tumors showed a better survival rate than those with CAII-negative tumors (P=0.024, log-rank test). CONCLUSION: CAII expression was related with stages and lymph node metastases in gastric carcinoma. The reduction of CAII expression in GC might promote tumor cell motility and contribute to tumor growth and metastasis.

Update on the role of C1GALT1 in cancer.

Cancer remains one of the most difficult diseases to treat. In the quest for early diagnoses to improve patient survival and prognosis, targeted therapies have become a hot research topic in recent years. Glycosylation is the most common posttranslational modification in mammalian cells. Core 1ß1,3-galactosyltransferase (C1GALT1) is a key glycosyltransferase in the glycosylation process and is the key enzyme in the formation of the core 1 structure on which most complex and branched O-glycans are formed. A recent study reported that C1GALT1 was aberrantly expressed in tumors. In cancer cells, C1GALT1 is regulated by different factors. In the present review, the expression of C1GALT1 in different tumors and its possible molecular mechanisms of action are described and the role of C1GALT1 in cancer development is discussed.

Emerging Roles of the Unique Molecular Chaperone Cosmc in the Regulation of Health and Disease.

The core-1 ß1-3galactosyltransferase-specific chaperone 1 (Cosmc) is a unique molecular chaperone of core-1 ß1-3galactosyltransferase(C1GALT1), which typically functions inside the endoplasmic reticulum (ER). Cosmc helps C1GALT1 to fold correctly and maintain activity. It also participates in the synthesis of the T antigen, O-glycan, together with C1GALT1. Cosmc is a multifaceted molecule with a wide range of roles and functions. It involves platelet production and the regulation of immune cell function. Besides that, the loss of function of Cosmc also facilitates the development of several diseases, such as inflammation diseases, immune-mediated diseases, and cancer. It suggests that Cosmc is a critical control point in diseases and that it should be regarded as a potential target for oncotherapy. It is essential to fully comprehend Cosmc's roles, as they may provide critical information about its involvement in disease development and pathogenesis. In this review, we summarize the recent progress in understanding the role of Cosmc in normal development and diseases.

Role of salivary glycopatterns for oral microbiota associated with gastric cancer.

Microbiota in the oral cavity plays an important role in maintaining human health. Our previous studies have revealed significant alterations of salivary glycopatterns in gastric cancer (GC) patients, but it is unclear whether these altered salivary glycopatterns can cause the dysbiosis of oral microbiota. In this study, the oral microbiome of healthy volunteers (HVs) and GC patients were detected. The neoglycoproteins were then synthesized according to the altered glycopatterns in GC patients and used to explore the effects of specific salivary glycopattern against oral microbiota. The results showed that five species were significantly increased (p < 0.05) while two species were significantly decreased (p < 0.01) in the saliva of GC patients compared with that of HVs. And the fucose-neoglycoproteins (30-100 µg/mL) could reduce the adhesion and toxicity of Aggregatibacter segnis (A. segnis) to oral cells (HOEC and CAL-27), change the glycan structures of lipopolysaccharide on the surface of A. segnis, and enhance the capacity of A. segnis to trigger innate immune responses. This study revealed that the changes of salivary protein glycopatterns in GC patients might contribute to the dysbiosis of oral microbiota, and had important implications in developing new carbohydrate drugs to maintain a balanced microbiota in the oral.

Safety assessment of multiple repeated percutaneous punctures for the collection of cerebrospinal fluid in rats.

The objective of this study was to examine the safety of multiple repeated percutaneous punctures of cisterna magna for collecting cerebrospinal fluid (CSF) and preliminarily determine the optimal time interval and volume at each collection. Sixty Wistar rats were randomly assigned to six groups: 10 d-0 µL, 10 d-100 µL (100 µL CSF collected at an interval of 10 days), 10 d-150 µL, 15 d-0 µL, 15 d-100 µL, and 15 d-150 µL. CSF was collected by percutaneous puncture of the cisterna magna at four time-points. Simultaneously, locomotor activity, cisterna magna pressure, and acetylcholine levels in the CSF were monitored. Compared with the 10 d-0 µL group, the escape latency by Morris water maze was significantly prolonged in the 10 d-100 µL and 10 d-150 µL groups (P<0.05). Compared with the 15 d-0 µL group, the indices of 15 d-100 µL and 15 d-150 µL groups had no significant differences. When compared with that at the first training, the exception of the 10 d-150 µL and 15 d-150 µL groups, significant differences in escape latency were found at the 6th attempt (P<0.05). Compared with baseline readings for each group, the cisterna magna pressure in the 10 d-150 µL group began to decrease significantly from the third measurement (P<0.05). The optimal time interval during four CSF collections (100 µL per collection) via cisterna magna percutaneous puncture was determined to be 15 days. The procedure did not significantly affect learning processes, performance, or other related indices.