Complementary Chinese Herbal Medicine Treatment is Associated with a Reduction of Surgical Rate in Patients with Dysfunctional Uterine Bleeding: A Propensity-Score Matched Cohort Study.

Background: Many patients with dysfunctional uterine bleeding (DUB) seek traditional medicine consultations. This study intended to investigate the association of complementary Chinese herbal medicine (CHM) with the surgery rate in patients with DUB in Taiwan. Methods: We enrolled 43,027 patients with newly diagnosed DUB (ICD-9-CM codes 626.8) from the National Health Insurance Research Database in Taiwan during the period of 1997 to 2010. Among them, 38,324 were CHM users, and 4703 did not receive CHM treatment. After performing a 1:1 propensity-score match based on patients' age (per 5 years), comorbidities, conventional drugs, childbirth status, duration from the diagnosis year of DUB and index year, there were an equal number (n=4642) of patients in the CHM cohort and non-CHM cohort. The outcome measurement was the comparison of incidences of surgical events, including hysterectomy and endometrial ablation, in the two cohorts before the end of 2013. Results: CHM users had a lower incidence of surgery than non-CHM users (adjusted HR 0.27, 95% CI: 0.22-0.33). The cumulative incidence of surgery was significantly lower in the CHM cohort during the follow-up period (Log rank test, p < 0.001). A total of 146 patients in the CHM cohort (4.99 per 1000 person-years) and 485 patients in the non-CHM cohort (20.19 per 1000 person-years) received surgery (adjusted HR 0.27, 95% CI: 0.22-0.33). CHM also reduced the risk of surgery in DUB patients with or without comorbidities. Regardless of childbirth status or whether patients took NSAIDs, tranexamic acid or progesterone, fewer patients in the CHM cohort underwent surgery than in the non-CHM cohort. The most commonly prescribed single herb and formula were Yi-Mu-Cao (Herba Leonuri) and Jia-Wei-Xiao-Yao-San, respectively. Conclusion: The real-world data revealed that CHM is associated with a reduced surgery rate in DUB patients. This information may be provided for further clinical investigations and policy-making.

Astrocyte-derived lactate aggravates brain injury of ischemic stroke in mice by promoting the formation of protein lactylation.

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes (Aldh1l1 CreERT2; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke.

Impact of Patient Head Posture on Lens Radiation Exposure During Cerebral Angiography.

BACKGROUND AND PURPOSE: Cerebral angiography remains crucial for detailed characterization and preoperative assessments for intracranial aneurysm. Despite its diagnostic importance, cerebral angiography poses challenges due to its invasiveness, the risk of neurological complications, and radiation exposure. To investigate the impact of head posture on lens radiation exposure during cerebral angiography, this study focused on the correlation between radiation doses to the eye lens, head flexion angles, and head size. MATERIALS AND METHODS: A retrospective analysis was performed on 20 patients who underwent cerebral angiography for unruptured intracranial aneurysms between October and November 2022. Radiation doses to the lens, which were measured in a prior prospective study using photoluminescent glass dosimeters, were analyzed alongside head flexion angles, anteroposterior (AP) head diameters, and kerma-area product (KAP) to evaluate their correlation with lens radiation exposure. The lateral radiation source is located on the left side of the patients. RESULTS: The cohort consisted of 20 patients (60% female, mean age: 62.3 ± 9.9 years). The radiation dose to the left eye (the eye closer to the x-ray source) was 2.8 times higher than that to the right eye (9.18 ± 3.31 mGy vs. 3.3 ± 0.60 mGy, P < 0.001). A strong positive correlation was observed between the left eye lens dose and head flexion angle (R = 0.815, P < 0.001). While the AP head diameter significantly correlated with the flexion angle, it showed no significant correlation with lens dose. The KAP was inversely correlated with both the left lens dose (R = -0.597, P = 0.005) and the flexion angle (R = -0.689, P < 0.001). CONCLUSIONS: Our findings underscore the significant impact of head posture on lens radiation exposure during cerebral angiography. Adjusting head positioning may provide a practical approach to reduce radiation exposure to the lens. Furthermore, it is worth noting that the left lens received more radiation than the right, likely due to the X-ray source being on the left side of the patient. ABBREVIATIONS: AP = anteroposterior; KAP = kerma-area product, PLD = photoluminescent glass dosimeter.

Is the tea or teacup good? The effect of visual and haptic sensory processing of teacups on the perception of tea flavor.

Prior research on the relationship between the taste, aroma and drinking utensils of beverages tends to focus on topics such as alcohol, sparkling beverages, juice, coffee, and hot chocolate. There is limited research focused on the interdependence between the perception of teacups and the tea taste. The literature has not yet found any research covering the impact of visual shape and the tactile sensation of teacups on the perception of tea flavor. Therefore, this study proposed six hypotheses related to the teacup shape and texture, teacup preference and taste and smell of tea. This study involved experimental design and questionnaire data collection, using a convenience sampling method to recruit 102 participants voluntarily. The research results are: (1) Age and gender have an impact on the taste and aroma perception of tea; (2) The width, height, rim thickness and smoothness of the teacup surface do have an impact on the perception of taste and fragrance of tea. (3) The preference of teacup played an intermediary effect between tea taste and the shape and texture of teacup. The implications of these findings on the perception of tea flavor are discussed.

Enhancement on CT for preoperative diagnosis of metastatic lymph nodes in thyroid cancer: a comparison across experience levels.

OBJECTIVES: To investigate the diagnostic performance and interobserver agreement of quantitative CT parameters indicating strong lymph node (LN) enhancement in differentiated thyroid cancer (DTC), comparing them with qualitative analysis by radiologists of varying experience. MATERIALS AND METHODS: This study included 463 LNs from 399 patients with DTC. Three radiologists independently analyzed strong LN enhancement on CT. Qualitative analysis of strong enhancement was defined as LN cortex showing greater enhancement than adjacent muscles on the arterial phase. Quantitative analysis included the mean attenuation value (MAV) of LN on arterial phase (LNA) and venous phase (LNV), LNA normalized to the common carotid artery (NAVCCA), internal jugular vein (NAVIJV), and sternocleidomastoid muscle (NAVSCM), attenuation difference [AD; (LNA - MAVSCM)], and relative washout ratio [((LNA - LNV)/LNA) × 100]. The interobserver agreement and diagnostic performance of the quantitative and qualitative analyses were evaluated. RESULTS: Interobserver agreement was excellent for all quantitative CT parameters (ICC, 0.83-0.94) and substantial for qualitative assessment (κ = 0.61). All CT parameters except for LNV showed good diagnostic performance for metastatic LNs (AUC, 0.81-0.85). NAVCCA (0.85, 95% CI: 0.8-0.9) and AD (0.85, 95% CI: 0.81-0.89) had the highest AUCs. All quantitative parameters except for NAVIJV had significantly higher AUCs than qualitative assessments by inexperienced radiologists, with no significant difference from assessments by an experienced radiologist. CONCLUSION: Quantitative assessment of LN enhancement on arterial phase CT showed higher interobserver agreement and AUC values than qualitative analysis by inexperienced radiologists, supporting the need for a standardized quantitative CT parameter-based model for determining strong LN enhancement. CLINICAL RELEVANCE STATEMENT: When assessing strong LN enhancement in DTC, quantitative CT parameters indicating strong enhancement can improve interobserver agreement, regardless of experience level. Therefore, the development of a standardized diagnostic model based on quantitative CT parameters might be necessary. KEY POINTS: Accurate preoperative assessment of LN metastasis in thyroid cancer is crucial. Quantitative CT parameters indicating strong LN enhancement demonstrated excellent interobserver agreement and good diagnostic performance. Quantitative assessment of contrast enhancement offers a more objective model for the identification of metastatic LNs.

Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta.

INTRODUCTION: Aging is one of the risk factors for the early onset of Alzheimer's disease (AD). We previously discovered that the age-dependent increase in Ubiquitin Conjugating Enzyme E2 N (UBE2N) plays a role in the accumulation of misfolded proteins through K63 ubiquitination, which has been linked to AD pathogenesis. However, the impact of UBE2N on amyloid pathology and clearance has remained unknown. RESULTS: We observed the elevated UBE2N during the amyloid beta (Aß) generation in the brains of 5×FAD, APP/PS1 mice, and patients with AD, in comparison to healthy individuals. UBE2N overexpression exacerbated amyloid deposition in 5×FAD mice and senescent monkeys, whereas knocking down UBE2N via CRISPR/Cas9 reduced Aß generation and cognitive deficiency. Moreover, pharmacological inhibition of UBE2N ameliorated Aß pathology and subsequent transcript defects in 5×FAD mice. DISCUSSION: We have discovered that age-dependent expression of UBE2N is a critical regulator of AD pathology. Our findings suggest that UBE2N could serve as a potential pharmacological target for the advancement of AD therapeutics. HIGHLIGHTS: Ubiquitin Conjugating Enzyme E2 N (UBE2N) level was elevated during amyloid beta (Aß) deposition in AD mouse and patients' brains. UBE2N exacerbated Aß generation in the AD mouse and senescent monkey. Drug inhibition of UBE2N ameliorated Aß pathology and cognitive deficiency.

Knockdown of miR-155 alleviates skin damage in rats with chronic spontaneous urticaria by modulating the JAK/STAT signaling pathway.

OBJECTIVE: The aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU). METHODS: The expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues. RESULTS: Knockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats. CONCLUSION: Knockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway.

Recent advances of PIWI-interacting RNA in cardiovascular diseases.

BACKGROUND: The relationship between noncoding RNAs (ncRNAs) and human diseases has been a hot topic of research, but the study of ncRNAs in cardiovascular diseases (CVDs) is still in its infancy. PIWI-interacting RNA (piRNA), a small ncRNA that binds to the PIWI protein to maintain genome stability by silencing transposons, was widely studied in germ lines and stem cells. In recent years, piRNA has been shown to be involved in key events of multiple CVDs through various epigenetic modifications, revealing the potential value of piRNA as a new biomarker or therapeutic target. CONCLUSION: This review explores origin, degradation, function, mechanism and important role of piRNA in CVDs, and the promising therapeutic targets of piRNA were summarized. This review provide a new strategy for the treatment of CVDs and lay a theoretical foundation for future research. KEY POINTS: piRNA can be used as a potential therapeutic target and biomaker in CVDs. piRNA influences apoptosis, inflammation and angiogenesis by regulating epigenetic modificaions. Critical knowledge gaps remain in the unifying piRNA nomenclature and PIWI-independent function.

Ginsenoside CK cooperates with bone mesenchymal stem cells to enhance angiogenesis post-stroke via GLUT1 and HIF-1α/VEGF pathway.

The transplantation of bone marrow mesenchymal stem cells (MSCs) in stroke is hindered by the restricted rates of survival and differentiation. Ginsenoside compound K (CK), is reported to have a neuroprotective effect and regulate energy metabolism. We applied CK to investigate if CK could promote the survival of MSCs and differentiation into brain microvascular endothelial-like cells (BMECs), thereby alleviating stroke symptoms. Therefore, transwell and middle cerebral artery occlusion (MCAO) models were used to mimic oxygen and glucose deprivation (OGD) in vitro and in vivo, respectively. Our results demonstrated that CK had a good affinity for GLUT1, which increased the expression of GLUT1 and the production of ATP, facilitated the proliferation and migration of MSCs, and activated the HIF-1α/VEGF signaling pathway to promote MSC differentiation. Moreover, CK cooperated with MSCs to protect BMECs, promote angiogenesis and vascular density, enhance neuronal and astrocytic proliferation, thereby reducing infarct volume and consequently improving neurobehavioral outcomes. These results suggest that the synergistic effects of CK and MSCs could potentially be a promising strategy for stroke.

Systematic characterization of the expression, prognosis and immune characteristics of PLOD family genes in breast cancer.

BACKGROUND: The expression patterns and prognostic value of Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family genes in breast cancer remain to be elucidated. METHODS: The expression levels, prognostic value, and biological function of PLODs were determined using Oncomine, cBioPortal, GEPIA, Timer, UALCAN, PrognoScan, GeneMANIA, Metascape, and breast cancer tissue microarrays. RESULTS: The expressions of PLOD1 and PLOD3 were upregulated in breast cancer tissues, indicating worse clinical stages. High expression levels of PLOD family genes were associated with worse disease-free survival and distant metastasis-free survival, while high expression levels of PLOD1 and PLOD3 were related to worse overall survival in all breast cancer patients. The levels of PLOD family genes were all significantly higher in the age ≤51 y group, HR-negative patients, and triple negative breast cancer (TNBC) patients. They are associated with tumor-infiltrating immune cells (TIICs), including CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells. According to co-expression gene analysis and functional enrichment, they are associated with protein hydroxylation, collagen biosynthesis and modifying enzymes, collagen metabolism, RNA splicing, extracellular matrix organization, VEGFA-VEGFR2 signaling pathway, and skeletal system development. Immunohistochemistry showed that the expressions of all PLOD family genes were significantly elevated in breast cancer tissues. PLOD1 expression was positively correlated with ER, TNBC status, and tumor grade. PLOD2 expression was positively connected with Ki-67 status. PLOD3 expression was positively related with age and tumor grade. CONCLUSIONS: PLOD family genes are novel potential prognostic biomarkers for breast cancer, and targeting PLOD inhibitors might be an effective strategy for breast cancer therapy.

Improving Microcystis aeruginosa removal efficiency through enhanced sonosensitivity of nitrogen-doped nanodiamonds.

Traditional methods for algae removal in drinking water treatment, such as coagulation and sedimentation, face challenges due to the negative charge on algae cells' surfaces, resulting in ineffective removal. Ultrasonic cavitation has shown promise in enhancing coagulation performance by disrupting extracellular polymer structures and improving cyanobacteria removal through various mechanisms like shear force and free radical reactions. However, the short lifespan and limited mass transfer distance of free radicals in conventional ultrasonic treatment lead to high energy consumption, limiting widespread application. To overcome these limitations and enhance energy efficiency, advanced carbon-based materials were developed and tested. Nitrogen-doped functional groups on nanodiamond surfaces were found to boost sonosensitivity by increasing the production of reactive oxygen species at the sonosensitizer-water interface. Utilizing low-power ultrasound (0.12 W/mL) in combination with N-ND treatment for 5 min, removal rates of Microcystis aeruginosa cells in water exceeded 90 %, with enhanced removal of algal organic matters and microcystins in water. Visualization through confocal microscopy highlighted the role of positively charged nitrogen-doped nanodiamonds in aggregating algae cells. The synergy between cell capturing and catalysis of N-ND indicates that efficient mass transfer of free radicals from the sonosensitizer's surface to the microalgae's surface is critical for promoting cyanobacteria floc formation. This study underscores the potential of employing a low-intensity ultrasound and N-ND system in effectively improving algae removal in water treatment processes.

Psychosocial factors in knee osteoarthritis: Scoping review of evidence and future opportunities.

OBJECTIVE: Identify, describe and produce an evidence map of studies investigating psychosocial factors association with, or effect on, clinical outcomes for people with knee osteoarthritis. METHODS: Scoping review of interventional and observational studies was performed. Medline (Ovid), Embase (Ovid), Cumulated Index in Nursing and Allied Health Literature, PsycInfo and Web of Science were searched on the 15th May 2023. Screening, data extraction and analysis was performed by two independent researchers. Extracted information included characteristics of studies plus which psychosocial factors were used to investigate association with, or effect on, clinical outcome(s). Descriptive statistics summarized the study design, temporal trend, geographic distribution, frequency of each psychosocial factor and whether associations/effects were observed. RESULTS: 23,065 records were screened, with 108 studies selected. Eighty-two percent of studies (n = 89/108) were cross-sectional in design. Number of studies increased over time and spanned 28 countries. Most research originated from the Americas region (55 %, 59/108). Twenty-four psychosocial factors (11 psychological, 13 social) were identified. Depression (47 %, n = 48/102) and education (28 %, n = 29/102) were the most frequently reported psychological and social factors, respectively. Psychological factors were often reported to have an association with/effect on pain (81 %, n = 71/88) and physical function (75 %, n = 56/74). Social factors were less frequently reported to have an association with or effect on pain (57 %, n = 46/81) and physical function (50 %, n = 18/36). CONCLUSION: Psychosocial factors are often associated with clinical outcomes for people with knee osteoarthritis. High-quality longitudinal studies examining a wide range of psychosocial factors across diverse cultural and geographical settings are key to continue informing the development of biopsychosocial models of care.

Size-inclusive advertising in the Asian fashion market: Female consumers' responses to a plus-size vs. Thin-size model in South Korea.

Global fashion brands have embraced size-inclusive advertising featuring plus-size models, yet the responses of Asian consumers to such advertising-where the average body size of women is smaller than in Western markets-have garnered little attention. This study, utilizing the S-O-R model, aimed to investigate whether the relationships among perceived actual and ideal self-congruence, perceived attractiveness and familiarity of a fashion model, and purchase intention vary based on the body size of the fashion model. We tested the hypothesized relationships using ANCOVA, confirmatory factor analysis, and multi-group structural equation modeling, analyzing 623 online survey responses from South Korean female consumers. Actual self-congruence had a greater influence on perceived familiarity in consumers exposed to a thin-sized model compared to those exposed to a plus-sized model. In contrast, ideal self-congruence had a more significant positive impact on the perceived physical attractiveness of the plus-size model than the thin-size model. Furthermore, the plus-size model's perceived physical attractiveness had a more significant positive effect on purchase intention than that of the thin-size model. This study highlights the importance of crafting advertising images that portray plus-size models as physically attractive to elicit favorable responses from Asian consumers.

CACSNet for automatic robust classification and segmentation of carotid artery calcification on panoramic radiographs using a cascaded deep learning network.

Stroke is one of the major causes of death worldwide, and is closely associated with atherosclerosis of the carotid artery. Panoramic radiographs (PRs) are routinely used in dental practice, and can be used to visualize carotid artery calcification (CAC). The purpose of this study was to automatically and robustly classify and segment CACs with large variations in size, shape, and location, and those overlapping with anatomical structures based on deep learning analysis of PRs. We developed a cascaded deep learning network (CACSNet) consisting of classification and segmentation networks for CACs on PRs. This network was trained on ground truth data accurately determined with reference to CT images using the Tversky loss function with optimized weights by balancing between precision and recall. CACSNet with EfficientNet-B4 achieved an AUC of 0.996, accuracy of 0.985, sensitivity of 0.980, and specificity of 0.988 in classification for normal or abnormal PRs. Segmentation performances for CAC lesions were 0.595 for the Jaccard index, 0.722 for the Dice similarity coefficient, 0.749 for precision, and 0.756 for recall. Our network demonstrated superior classification performance to previous methods based on PRs, and had comparable segmentation performance to studies based on other imaging modalities. Therefore, CACSNet can be used for robust classification and segmentation of CAC lesions that are morphologically variable and overlap with surrounding structures over the entire posterior inferior region of the mandibular angle on PRs.

Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology.

ABSTRACT: Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor (AR) gene, which encodes a ligand-dependent transcription factor. The mutant AR protein, characterized by polyglutamine expansion, is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in SBMA patients. These aggregates alter protein-protein interactions and compromise transcriptional activity. In this study, we reported that in both cultured N2a cells and mouse brain, mutant AR with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-derived neurotrophic factor (MANF). Overexpression of MANF ameliorated the neurotoxicity of mutant AR through the inhibition of mutant AR aggregation. Conversely, knocking down endogenous MANF in the mouse brain exacerbated neuronal damage and mutant AR aggregation. Our findings suggest that inhibition of MANF expression by mutant AR is a potential mechanism underlying neurodegeneration in SBMA.

Chloroplast Genomes of Vitis flexuosa and Vitis amurensis: Molecular Structure, Phylogenetic, and Comparative Analyses for Wild Plant Conservation.

The chloroplast genome plays a crucial role in elucidating genetic diversity and phylogenetic relationships. Vitis vinifera L. (grapevine) is an economically important species, prompting exploration of wild genetic resources to enhance stress resilience. We meticulously assembled the chloroplast genomes of two Korean Vitis L. species, V. flexuosa Thunb. and V. amurensis Rupr., contributing valuable data to the Korea Crop Wild Relatives inventory. Through exhaustive specimen collection spanning diverse ecological niches across South Korea, we ensured comprehensive representation of genetic diversity. Our analysis, which included rigorous codon usage bias assessment and repeat analysis, provides valuable insights into amino acid preferences and facilitates the identification of potential molecular markers. The assembled chloroplast genomes were subjected to meticulous annotation, revealing divergence hotspots enriched with nucleotide diversity, thereby presenting promising candidates for DNA barcodes. Additionally, phylogenetic analysis reaffirmed intra-genus relationships and identified related crops, shedding light on evolutionary patterns within the genus. Comparative examination with chloroplast genomes of other crops uncovered conserved sequences and variable regions, offering critical insights into genetic evolution and adaptation. Our study advances the understanding of chloroplast genomes, genetic diversity, and phylogenetic relationships within Vitis species, thereby laying a foundation for enhancing grapevine genetic diversity and resilience to environmental challenges.

The function and therapeutic potential of transfer RNA-derived small RNAs in cardiovascular diseases: A review.

Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs.

NAT10-mediated ac4C modification promotes stemness and chemoresistance of colon cancer by stabilizing NANOGP8.

Background: Colon cancer (CC) stem cells can self-renew as well as expand, thereby promoting tumor progression and conferring resistance to chemotherapeutic agents. The acetyltransferase NAT10 mediates N4-acetylcytidine (ac4C) modification, which in turn drives tumorigenesis, metastasis, stemness properties maintenance, and cell fate decisions. Nonetheless, the specific involvement of ac4C modification mediated by NAT10 in regulating stemness and chemosensitivity in CC remains undetermined. Methods: The levels of NAT10 in normal colon and chemoresistant CC tissues were determined utilizing quantitative real-time polymerase chain reaction alongside immunohistochemistry. Assessing cancer cell stemness and chemosensitivity was conducted by various methods including spheroid and colony formation, western blotting, and flow cytometry. RNA-Seq was used to identify target genes, and RNA immunoprecipitation analysis was used to explore the potential mechanisms. Results: We observed NAT10 overexpression and increased ac4C modification levels in chemoresistant CC tissues. The in vivo and in vitro analysis findings suggested that NAT10 promoted CC cell stemness while suppressing their chemosensitivity. Conversely, Remodelin, a NAT10-specific inhibitor, enhanced CC cell chemosensitivity. Mechanistically, NAT10 increased the level of NANOGP8 ac4C modification and promoted NANOGP8 mRNA stability. Conclusions: NAT10 promotes the maintenance of stemness and chemoresistance in CC cells by augmenting the mRNA stability of NANOGP8. The inhibition of NAT10 via Remodelin improves chemotherapeutic efficacy and impedes CC progression.

Automatic segmentation and classification of frontal sinuses for sex determination from CBCT scans using a two-stage anatomy-guided attention network.

Sex determination is essential for identifying unidentified individuals, particularly in forensic contexts. Traditional methods for sex determination involve manual measurements of skeletal features on CBCT scans. However, these manual measurements are labor-intensive, time-consuming, and error-prone. The purpose of this study was to automatically and accurately determine sex on a CBCT scan using a two-stage anatomy-guided attention network (SDetNet). SDetNet consisted of a 2D frontal sinus segmentation network (FSNet) and a 3D anatomy-guided attention network (SDNet). FSNet segmented frontal sinus regions in the CBCT images and extracted regions of interest (ROIs) near them. Then, the ROIs were fed into SDNet to predict sex accurately. To improve sex determination performance, we proposed multi-channel inputs (MSIs) and an anatomy-guided attention module (AGAM), which encouraged SDetNet to learn differences in the anatomical context of the frontal sinus between males and females. SDetNet showed superior sex determination performance in the area under the receiver operating characteristic curve, accuracy, Brier score, and specificity compared with the other 3D CNNs. Moreover, the results of ablation studies showed a notable improvement in sex determination with the embedding of both MSI and AGAM. Consequently, SDetNet demonstrated automatic and accurate sex determination by learning the anatomical context information of the frontal sinus on CBCT scans.

Association of IL­6 and MMP­3 gene polymorphisms with adolescent idiopathic scoliosis: A systematic review and meta­analysis.

The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3 (MMP-3) rs3025058 locus gene polymorphisms may be associated with AIS susceptibility, which has been controversial and needs to be further confirmed by updated meta-analysis. The aim of the present study was to investigate the association of MMP-3 rs3025058 and IL-6 rs1800795 single nucleotide polymorphisms (SNPs) with susceptibility to AIS. All relevant articles that met the criteria were retrieved and included, and the publication dates were limited from January 2005 to December 2023. The allele frequencies and different genotype frequencies of IL-6 rs1800795 and MMP-3 rs3025058 loci in each study were extracted and statistically analyzed by ReviewManager 5.4 software, and the odds ratio (OR) and 95% confidence interval (95% CI) of different genetic models were calculated. The results of the meta-analysis showed that there was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS. The allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility (5A vs. 6A, OR=1.18; 95% CI, 1.04-1.33; 5A5A vs. 6A6A, OR=1.65; 95% CI, 1.23-2.21; and 5A5A vs. 5A6A + 6A6A, OR=1.54; 95% CI, 1.19-1.99). Results of subgroup analysis revealed that the allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility in the Caucasian population, and the susceptibility of AIS was associated with the genotype 5A5A of MMP-3 rs3025058 SNP in an Asian population. There was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS, while the allele 5A of MMP-3 rs3025058 locus was associated with the susceptibility to AIS, especially in the Caucasian population.