Methylation modifications in tRNA and associated disorders: Current research and potential therapeutic targets.

High-throughput sequencing has sparked increased research interest in RNA modifications, particularly tRNA methylation, and its connection to various diseases. However, the precise mechanisms underpinning the development of these diseases remain largely elusive. This review sheds light on the roles of several tRNA methylations (m1A, m3C, m5C, m1G, m2G, m7G, m5U, and Nm) in diverse biological functions, including metabolic processing, stability, protein interactions, and mitochondrial activities. It further outlines diseases linked to aberrant tRNA modifications, related enzymes, and potential underlying mechanisms. Moreover, disruptions in tRNA regulation and abnormalities in tRNA-derived small RNAs (tsRNAs) contribute to disease pathogenesis, highlighting their potential as biomarkers for disease diagnosis. The review also delves into the exploration of drugs development targeting tRNA methylation enzymes, emphasizing the therapeutic prospects of modulating these processes. Continued research is imperative for a comprehensive comprehension and integration of these molecular mechanisms in disease diagnosis and treatment.

The preferred surgical choice for intermediate-risk papillary thyroid cancer: total thyroidectomy or lobectomy? A systematic review and meta-analysis.

BACKGROUND: The optimal surgical approach for intermediate-risk papillary thyroid carcinoma (IR-PTC) (according to ATA definition), whether total thyroidectomy (TT) or lobectomy (LT), has remained a contentious clinical gray area for several decades. This systematic review and meta-analysis aim to provide robust evidence and address this clinical dilemma comprehensively. MATERIALS AND METHODS: A comprehensive literature search was conducted in Pubmed, Embase, Web of Science, and the Cochrane Library from 1st January 2009 to 29th December 2023 to evaluate the impact of different surgical options (TT or LT) on patients with IR-PTC. The primary outcomes included survival, recurrence rates, and postoperative complications. I2 and sensitivity analysis was used to explore the heterogeneity. RESULTS: A total of 8 studies involving 2984 participants were included in this meta-analysis and systematic review. The results indicated that LT was a superior choice for mitigating complications compared to TT [risk ratio (RR), 0.32; 95% CI: 0.24-0.44, P <0.01], particularly for transient complications (RR, 0.24; 95% CI: 0.08-0.65, P <0.01), such as the transient parathyroid dysfunction (RR, 0.04; 95% CI: 0.01-0.15, P <0.01). However, TT did not increase the risk of recurrent laryngeal nerve palsy (RR, 0.78; 95% CI: 0.24-2.47, P =0.67), hemorrhage/seroma (RR, 0.77; 95% CI: 0.48-1.25, P =0.30), and permanent complications (RR, 0.18; 95% CI: 0.02-1.42, P =0.10). Besides, both LT and TT presented similar effect on survival outcomes (overall survival: RR, 1.00; 95% CI: 0.97-1.03, P =0.92, disease-specific survival: RR, 0.99; 95% CI: 0.97-1.02, P =0.69, recurrence-free survival: RR, 1.00; 95% CI: 0.96-1.05, P =0.86), recurrence (RR, 1.05; 95% CI: 0.76-1.46, P =0.76). CONCLUSION: The present meta-analysis revealed that TT did not yield improved outcomes in IR-PTC patients, but was associated with an increased incidence of temporary complications. In light of these findings, it may be advisable to consider LT as the optimal choice for IR-PTC patients.

Structural elucidation and immunomodulatory activities in vitro of type I and II arabinogalactans from different origins of Astragalus membranaceus.

Astragalus membranaceus polysaccharide (APS) possesses excellent immunomodulatory activity. However, there are several studies on the structural characterization of APS. Here, we aimed to elucidate the repeating units of polysaccharides (APS1, 106.5 kDa; APS2, 114.5 kDa) obtained from different Astragalus membranaceus origins and further investigated their immunomodulatory activities. Based on structural analysis, types of the two polysaccharides were identified as arabinogalactan-I (AG-I) and arabinogalactan-II (AG-II), and co-elution of arabinogalactans (AGs) and α-glucan was observed. The backbone of AG-I was 1,4-linked ß-Galp occasionally substituted by α-Araf at O-2 and/or O-3. AG-II was a highly branched polysaccharide with long branches of α-Araf, which were attached to the O-3 of 1,6-linked ß-Galp of the backbone. The presence of AGs in A. membranaceus was confirmed for the first time. The two polysaccharides could promote the expression of IL-6, IL-1ß and TNF-α in RAW264.7 cells via MAPKs and NF-κB signaling pathways. The constants for APS1 and APS2 binding to Toll-like receptor 4 (TLR4) were 1.83 × 10-5 and 2.08 × 10-6, respectively. Notably, APS2 showed better immunomodulatory activity than APS1, possibly because APS2 contained more AGs. Hence, the results suggested that AGs were the vital components of APS in the immunomodulatory effect.

The ultrasound-based radiomics-clinical machine learning model to predict papillary thyroid microcarcinoma in TI-RADS 3 nodules.

Background: Conventional ultrasound (CUS) technology has proven to be successful in the identification of thyroid nodules. Moreover, the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) was developed for the purpose of evaluating the risk of thyroid nodules based on ultrasound imaging. Nevertheless, identifying papillary thyroid microcarcinoma (PTMC) from TI-RADS 3 nodules using this system can be difficult due to overlapping morphological features. The main objective of this study was to investigate the efficacy of a machine learning model that utilizes ultrasound-based radiomics features and clinical information in accurately predicting the presence of PTMC in TI-RADS 3 nodules. Methods: A total of 221 patients with TI-RADS 3 nodules were included, consisting of 91 cases of PTMC and 130 benign thyroid nodules. They were randomly divided into training and test cohort in an 8:2 ratio. Radiomics features were extracted from CUS images by manually outlining the targets, while clinical parameters were obtained from electronic medical records. The radiomics model, clinical model, and combined model were constructed and validated to distinguish between PTMC and benign thyroid nodules. Radiomics variables were extracted via the Pyradiomics package (V1.3.0). Moreover, least absolute shrinkage and selection operator (LASSO) regression was used for feature selection. Light Gradient Boosting Machine (LightGBM) was employed to build both radiomics and clinical models. Ultimately, a radiomics-clinical model, which fused radiomics features with clinical information, was developed. Results: Among a total of 1,477 radiomics features, fifteen features that were found to be associated with PTMC through univariate analysis and LASSO regression were selected for the development of the radiomics model. The combined "radiomics-clinical" model demonstrated superior diagnostic accuracy compared to the clinical model for distinguishing PTMC in both the training dataset [area under receiver operating curve (AUC): 0.975 vs. 0.845] and the validation dataset (AUC: 0.898 vs. 0.811). We constructed a radiomics-clinical nomogram, and the clinical applicability was confirmed through decision curve analysis. Conclusions: Utilizing an ultrasound-based radiomics approach has proven to be effective in predicting PTMC in patients with TI-RADS 3 nodules.

Predicting papillary thyroid microcarcinoma in American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 3 nodules: radiomics analysis based on intratumoral and peritumoral ultrasound images.

Background: A subset of patients undergoing thyroid surgery for presumed benign thyroid disease presented with papillary thyroid microcarcinoma (PTMC). A non-invasive and precise method for early recognition of PTMC are urgently needed. The aim of this study was to construct and validate a nomogram that combines intratumoral and peritumoral radiomics features as well as clinical features for predicting PTMC in the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 3 nodules using ultrasonography. Methods: A retrospective review was conducted on a cohort of 221 patients who presented with ACR TI-RADS 3 nodules. These patients were subsequently pathologically diagnosed with either PTMC or benign thyroid nodules. These patients were randomly divided into a training and test cohort with an 8:2 ratio for developing the clinical model, intratumor-region model, peritumor-region model and the combined-region model respectively. The radiomics features were extracted from ultrasound (US) images of each patient. We employed K-nearest neighbor (KNN) model as the base model for building the radiomics signature and clinical signature. Finally, a radiomics-clinical nomogram that combined intratumoral and peritumoral radiomics features as well as clinical features was developed. The prediction performance of each model was assessed by the area under the curve (AUC), sensitivity, specificity and calibration curve. Results: A total of 23 radiomics features were selected to develop radiomics models. The combined-region radiomics model showed favorable prediction efficiency in both the training dataset (AUC: 0.955) and the test dataset (AUC: 0.923). A radiomics-clinical nomogram was constructed and achieved excellent calibration and discrimination, which yielded an AUC value of 0.950, a sensitivity of 0.950 and a specificity of 0.920. Conclusions: This study proposed the nomogram that contributes to the accurate and intuitive identification of PTMC in ACR TI-RADS 3 nodules.

Trace Small Molecular/Nano-Colloidal Multiscale Electrolyte Additives Enable Ultra-Long Lifespan of Zinc Metal Anodes.

Electrolyte additives are efficient to improve the performance of aqueous zinc-ion batteries (AZIBs), yet the current electrolyte additives are limited to fully water-soluble additives (FWAs) and water-insoluble additives (WIAs). Herein, trace slightly water-soluble additives (SWAs) of zinc acetylacetonate (ZAA) were introduced to aqueous ZnSO4 electrolytes. The SWA system of ZAA is composed of a FWA part and a WIA part in a dynamic manner of dissolution equilibrium. The FWA part exists as soluble small molecules, which efficiently regulate Zn2+ ion solvation structure, while the WIA part exists as insoluble nano-colloids, which in-situ form a thick and robust solid electrolyte interface film on zinc metal anodes (ZMAs). Such small molecular/nano-colloidal multiscale electrolyte additives of ZAA are capable to not only improve ionic conductivity and transference number but also inhibit corrosion, hydrogen evolution, and Zn dendrite on ZMAs. The SWA-based Zn∥Zn half battery delivers a superb cumulative plating capacity of 15 Ah cm-2 under 1 mAh cm-2 and 20 mA cm-2, and the SWA-based NH4V4O10∥Zn pouch cell obtains a capacity retention of 67.8% within 4000 cycles under 4 A g-1. The study provides innovative insights for rational design of electrolyte additives, which may pave the way for the practicality of AZIBs.

Degradation of Angelica sinensis polysaccharide: Structures and protective activities against ethanol-induced acute liver injury.

Angelica sinensis polysaccharide (ASP) possesses diverse bioactivities; however, its metabolic fate following oral administration remains poorly understood. To intuitively determine its intestinal digestion behavior after oral administration, ASP was labeled with fluorescein, and it was found to accumulate and be degraded in the cecum and colon. Therefore, we investigated the in vitro enzymatic degradation behavior and identified the products. The results showed that ASP could be degraded into fragments with molecular weights similar to those of the fragments observed in vivo. Structural characterization revealed that ASP is a highly branched acid heteropolysaccharide with AG type II domains, and its backbone is predominantly composed of 1,3-Galp, →3,6)-Galp-(1→6)-Galp-(1→, 1,4-Manp, 1,4-Rhap, 1,3-Glcp, 1,2,3,4-Galp, 1,3,4,6-Galp, 1,3,4-GalAp and 1,4-GlcAp, with branches of Araf, Glcp and Galp. In addition, the high molecular weight enzymatic degradation products (ASP H) maintained a backbone structure almost identical to that of ASP, but exhibited only partial branch changes. Then, the results of ethanol-induced acute liver injury experiments revealed that ASP and ASP H reduced the expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and malondialdehyde (MDA) and increased the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels, thereby relieving ethanol-induced acute liver injury.

Elimination of subtelomeric repeat sequences exerts little effect on telomere essential functions in Saccharomyces cerevisiae.

Telomeres, which are chromosomal end structures, play a crucial role in maintaining genome stability and integrity in eukaryotes. In the baker's yeast Saccharomyces cerevisiae, the X- and Y'-elements are subtelomeric repetitive sequences found in all 32 and 17 telomeres, respectively. While the Y'-elements serve as a backup for telomere functions in cells lacking telomerase, the function of the X-elements remains unclear. This study utilized the S. cerevisiae strain SY12, which has three chromosomes and six telomeres, to investigate the role of X-elements (as well as Y'-elements) in telomere maintenance. Deletion of Y'-elements (SY12YΔ), X-elements (SY12XYΔ+Y), or both X- and Y'-elements (SY12XYΔ) did not impact the length of the terminal TG1-3 tracks or telomere silencing. However, inactivation of telomerase in SY12YΔ, SY12XYΔ+Y, and SY12XYΔ cells resulted in cellular senescence and the generation of survivors. These survivors either maintained their telomeres through homologous recombination-dependent TG1-3 track elongation or underwent microhomology-mediated intra-chromosomal end-to-end joining. Our findings indicate the non-essential role of subtelomeric X- and Y'-elements in telomere regulation in both telomerase-proficient and telomerase-null cells and suggest that these elements may represent remnants of S. cerevisiae genome evolution. Furthermore, strains with fewer or no subtelomeric elements exhibit more concise telomere structures and offer potential models for future studies in telomere biology.

CsLHY positively regulates cold tolerance by activating CsSWEET17 in tea plants.

Low temperature is one of the most important environmental factors limiting tea plants' geographic distribution and severely affects spring tea's yield and quality. Circadian components contribute to plant responses to low temperatures; however, comparatively little is known about these components in tea plants. In this study, we identified a core clock component the LATE ELONGATED HYPOCOTYL, CsLHY, which is mainly expressed in tea plants' mature leaves, flowers, and roots. Notably, CsLHY maintained its circadian rhythmicity of expression in summer, but was disrupted in winter and held a high expression level. Meanwhile, we found that CsLHY expression rhythm was not affected by different photoperiods but was quickly broken by cold, and the low temperature induced and kept CsLHY expression at a relatively high level. Yeast one-hybrid and dual-luciferase assays confirmed that CsLHY can bind to the promoter of Sugars Will Eventually be Exported Transporters 17 (CsSWEET17) and function as a transcriptional activator. Furthermore, suppression of CsLHY expression in tea leaves not only reduced CsSWEET17 expression but also impaired the freezing tolerance of leaves compared to the control. Our results demonstrate that CsLHY plays a positive role in the low-temperature response of tea plants by regulating CsSWEET17 when considered together.

Intestinal lymphatic transport of Smilax china L. pectic polysaccharide via Peyer's patches and its uptake and transport mechanisms in mononuclear phagocytes.

Recently, the intestinal lymphatic transport based on Peyer's patches (PPs) is emerging as a promising absorption pathway for natural polysaccharides. Herein, the aim of this study is to investigate the PP-based oral absorption of a pectic polysaccharide from Smilax china L. (SCLP), as well as its uptake and transport mechanisms in related immune cells. Taking advantages of the traceability of fluorescently labeled SCLP, we confirmed that SCLP could be absorbed into PPs and captured by their mononuclear phagocytes (dendritic cells and macrophages) following oral administration. Subsequently, the systematic in vitro study suggested that the endocytic mechanisms of SCLP by model mononuclear phagocytes (BMDCs and RAW264.7 cells) mainly involved caveolae-mediated endocytosis, macropinocytosis and phagocytosis. More importantly, SCLP directly binds and interacts with toll-like receptor 2 (TLR2) and galectin 3 (Gal-3) receptor, and was taken up by mononuclear phagocytes in receptor-mediated manner. After internalization, SCLP was intracellularly transported primarily through endolysosomal pathway and ultimately localized in lysosomes. In summary, this work reveals novel information and perspectives about the in vivo fate of SCLP, which will contribute to further research and utilization of SCLP and other pectic polysaccharides.

Anti-α-1,4-D-polygalacturonic acid antibodies as a new biomarker for juvenile idiopathic arthritis.

OBJECTIVE: Diagnosing juvenile idiopathic arthritis (JIA) is challenging. Our study aimed to investigate the clinical significance of anti-α-1,4-D-polygalacturonic acid (PGA) antibodies in JIA, focusing on their role in diagnosis and assessing disease activity. METHODS: In this prospective case-control study, we examined variations in serum levels of PGA-IgA and PGA-IgG among children with different types of JIA and healthy controls. Serum PGA-IgA and PGA-IgG levels were assessed concurrently in children with active and inactive JIA. RESULTS: This study included 126 patients diagnosed with JIA, 13 neonates, and 76 healthy children. Serum PGA-IgA and PGA-IgG levels were assessed, which revealed significant differences in PGA-IgA levels between various JIA subtypes and controls. An analysis of PGA-IgA levels in various JIA states revealed a statistically significant difference. Receiver operating characteristic (ROC) analysis demonstrated the robust predictive capability of PGA-IgA, with an AUC of 0.879 (p < 0.001), along with a specificity of 0.842 and sensitivity of 0.848. CONCLUSION: Increased levels of anti-PGA antibodies, particularly PGA-IgA, were significantly associated with JIA. PGA-IgA may serve as a sensitive biomarker for disease activity in JIA and could potentially aid in the diagnosis of JIA. Key Points • This study found a significant correlation between blood levels of PGA-IgA and juvenile idiopathic arthritis (JIA), which may provide valuable diagnostic insights. • PGA-IgA shows potential as a sensitive biomarker for the assessment of disease activity in JIA patients, helping to determine disease activity.

Efficient wastewater disinfection using a novel microwave discharge electrodeless ultraviolet system with ozone at an ultra-low dose.

Microwave discharge electrodeless lamp (MDEL) is a novel ultraviolet (UV) light source. Synergistic disinfection using UV light emitted by MDEL (MWUV) coupled with ozone (O3) at an ultra-low dose was investigated. Escherichia coli and Bacillus subtilis were deactivated more effectively by MWUV/O3 than by either MWUV or O3 alone. MWUV/O3 treatment using an O3 concentration of 0.4 mg/L gave an E. coli inactivation rate of 5.52 log. The photoreactivation degree and rate of E. coli were lower after inactivation by MWUV/O3 treatment than after MWUV treatment alone. The maximum photoreactivation rates after the MWUV/O3 and MWUV treatments were 2.90% and 16.08%, respectively. MWUV/O3 disinfection also inhibited dark resurrection of E. coli and gave a maximum dark resurrection rate of 0.0036%. Electron paramagnetic resonance spectroscopy indicated that more hydroxyl radicals were generated during MWUV/O3 treatment. Scanning electron microscopy and laser confocal scanning microscopy observations indicated that O3 played a key role in breaking down the cell structure. MWUV/O3 treatment gave a good disinfection effect on fecal coliform bacteria in actual domestic wastewater. The results indicated that inactivation of bacteria can be more effectively achieved by MWUV treatment with O3.

Cost-effectiveness analysis of the oral health promotion model in rural primary schools in Guangxi Zhuang Autonomous Region / 口腔疾病防治

Objective@#To evaluate the caries preventive effect and economic outcome of an oral health promotion model in rural primary schools in Guangxi Zhuang Autonomous Region.@*Methods@# In November 2015, a baseline survey was conducted on the caries prevalence of rural first graders in program areas, and then a program intervention was carried out on the first graders of target primary schools. The intervention methods included the distribution of oral health care products, oral health education, teacher training, etc. In 2020, the method of cluster random sampling was adopted to include the sixth graders who received the program intervention as first graders and were still available in 2020 as the intervention group. During this period, the sixth graders transferred from foreign schools who failed to receive the program intervention as first graders were included in the non-intervention group. The caries preventive effect was evaluated by analyzing the caries epidemiological data of 2 652 children aged 11-13 years, comparing the intervention and non-intervention group. The cost of the program was estimated by the structural analysis method. A decision tree model was established by TreeAge pro2019 and incorporated into the effect parameters and cost parameters for cost-effectiveness analysis and sensitivity analysis.@* Results @# The prevalence of caries in the intervention group was 54.8%, and the mean DMFT was 1.36 ± 1.64, both of which were lower than those in the non-intervention group. The difference in prevalence and mean DMFT between the two groups was statistically significant (P < 0.05). It costs CNY 319.83 per child to reduce suffering from caries. The number of patients with caries in the intervention group was the most sensitive indicator of an economic effect. The probability of a cost-effectiveness advantage for the program was 92.2%. @*Conclusion @# This oral health promotion model used in rural schools demonstrated a caries preventive effect that was very likely economically advantageous. It is of practical significance to improve and promote this model in the Guangxi Zhuang Autonomous Region.