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Background: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) reduce the risk of hepatocellular carcinoma (HCC) in patients of hepatitis B. This study compared the difference between ETV and TDF on risk of HCC recurrence and mortality in patients with HBV-related HCC after curative intent treatment. Methods: Patients with HBV-related HCC who received HCC treatment (surgery or radiofrequency ablation [RFA]) and underwent long-term ETV or TDF therapy were retrospectively included. Baseline characteristics including age, sex, antiviral therapy, liver reserve, HCC stages, pathology reports and treatment modality were obtained. The risk of tumor recurrence, all-cause mortality, HCC-related mortality, and liver function were compared. Results: We identified 390 HBV-related HCC patients with curative intent treatment for HCC and treated with ETV (n = 328) or TDF (n = 62) between January 2011 and December 2020. The median age was 60 years, and 90.7% patients were males. After a median follow-up of 29 months, 186 patients developed recurrent HCC and 111 died. The baseline characteristics were comparable except more ALBI grade 3 patients in TDF group (76% vs. 48%, P

Abstract Background This study compared the survival outcomes after thermal ablation versus wedge resection in patients with stage I non-small cell lung cancer (NSCLC) ≤ 2 cm. Methods Data from the United States (US) National Cancer Institute Surveillance Epidemiology and End Results (SEER) database from 2004 to 2019 were retrospectively analyzed. Patients with stage I NSCLC and lesions ≤ 2 cm who received thermal ablation or wedge resection were included. Patients who received chemotherapy or radiotherapy were excluded. Propensity-score matching (PSM) was applied to balance the baseline characteristics between patients who underwent the two procedures. Results Univariate and Cox regression analyses were performed to determine the associations between study variables, overall survival (OS), and cancer-specific survival (CSS). After PSM, 328 patients remained for analysis. Multivariable Cox regression analysis revealed, compared to wedge resection, thermal ablation was significantly associated with a greater risk of poor OS (adjusted HR [aHR]: 1.34, 95% CI: 1.09–1.63, p = 0.004) but not CSS (aHR: 1.28, 95% CI: 0.96–1.71, p = 0.094). In stratified analyses, no significant differences were observed with respect to OS and CSS between the two procedures regardless of histology and grade. In patients with tumor size 1 to 2 cm, compared to wedge resection, thermal ablation was significantly associated with a higher risk of poor OS (aHR: 1.35, 95% CI: 1.10–1.66, p = 0.004). In contrast, no significant difference was found on OS and CSS between thermal ablation and wedge resection among those with tumor size

Abstract Background We compared magnetic resonance imaging (MRI) turbo spin-echo images reconstructed using a deep learning technique (TSE-DL) with standard turbo spin-echo (TSE-SD) images of the lumbar spine regarding image quality and detection performance of common degenerative pathologies. Methods This prospective, single-center study included 31 patients (15 males and 16 females; aged 51 ± 16 years (mean ± standard deviation)) who underwent lumbar spine exams with both TSE-SD and TSE-DL acquisitions for degenerative spine diseases. Images were analyzed by two radiologists and assessed for qualitative image quality using a 4-point Likert scale, quantitative signal-to-noise ratio (SNR) of anatomic landmarks, and detection of common pathologies. Paired-sample t, Wilcoxon, and McNemar tests, unweighted/linearly weighted Cohen κ statistics, and intraclass correlation coefficients were used. Results Scan time for TSE-DL and TSE-SD protocols was 2:55 and 5:17 min:s, respectively. The overall image quality was either significantly higher for TSE-DL or not significantly different between TSE-SD and TSE-DL. TSE-DL demonstrated higher SNR and subject noise scores than TSE-SD. For pathology detection, the interreader agreement was substantial to almost perfect for TSE-DL, with κ values ranging from 0.61 to 1.00; the interprotocol agreement was almost perfect for both readers, with κ values ranging from 0.84 to 1.00. There was no significant difference in the diagnostic confidence or detection rate of common pathologies between the two sequences (p ≥ 0.081). Conclusions TSE-DL allowed for a 45% reduction in scan time over TSE-SD in lumbar spine MRI without compromising the overall image quality and showed comparable detection performance of common pathologies in the evaluation of degenerative lumbar spine changes. Relevance statement Deep learning-reconstructed lumbar spine MRI protocol enabled a 45% reduction in scan time compared with conventional reconstruction, with comparable image quality and detection performance of common degenerative pathologies. Key points • Lumbar spine MRI with deep learning reconstruction has broad application prospects. • Deep learning reconstruction of lumbar spine MRI saved 45% scan time without compromising overall image quality. • When compared with standard sequences, deep learning reconstruction showed similar detection performance of common degenerative lumbar spine pathologies. Graphical Abstract

Abstract Background Whole plant senescence represents the final stage in the life cycle of annual plants, characterized by the decomposition of aging organs and transfer of nutrients to seeds, thereby ensuring the survival of next generation. However, the transcriptomic profile of vegetative organs during this death process remains to be fully elucidated, especially regarding the distinctions between natural programmed death and artificial sudden death induced by herbicide. Results Differential genes expression analysis using RNA-seq in leaves and roots of Arabidopsis thaliana revealed that natural senescence commenced in leaves at 45–52 days after planting, followed by roots initiated at 52–60 days. Additionally, both organs exhibited similarities with artificially induced senescence by glyphosate. Transcription factors Rap2.6L and WKRY75 appeared to serve as central mediators of regulatory changes during natural senescence, as indicated by co-expression networks. Furthermore, the upregulation of RRTF1, exclusively observed during natural death, suggested its role as a regulator of jasmonic acid and reactive oxygen species (ROS) responses, potentially triggering nitrogen recycling in leaves, such as the glutamate dehydrogenase (GDH) shunt. Root senescence was characterized by the activation of AMT2;1 and GLN1;3, facilitating ammonium availability for root-to-shoot translocation, likely under the regulation of PDF2.1. Conclusions Our study offers valuable insights into the transcriptomic interplay between phytohormones and ROS during whole plant senescence. We observed distinct regulatory networks governing nitrogen utilization in leaf and root senescence processes. Furthermore, the efficient allocation of energy from vegetative organs to seeds emerges as a critical determinant of population sustainability of annual Arabidopsis.

This comprehensive review assessed the integration of robotics and artificial intelligence (AI) in dentistry, offering a transparent overview of developments across dental fields. Covering articles in prosthodontics, orthodontics, implantology, surgery, and radiology, the review included 39 articles on robotics and 16 on AI. Screening adhered to PRISMA guidelines, with searches conducted on Medline, Google Scholar, and IEEE. Incorporating the search strategy, the review used keywords related to dentistry, robotics, and AI. For robotics, 296 articles were screened, resulting in 39 qualifying for qualitative synthesis. A separate AI search on PubMed identified 142 studies within the last decade, with 16 studies selected for a detailed full-text analysis, offering a consolidated overview of the current state-of-the-art knowledge in the AI domain. Geographic distribution highlighted East Asia as a major research contributor. The findings indicate an increasing trend in dentistry robotics since 2000 and, particularly since 2016, in AI dentistry. The majority of the literature fell under the category of basic research. The technology readiness level did not cross “three” (proof of concept) in 41% of all articles. Therefore, the overall literature quality remains low, particularly regarding clinical validation.

Abstract Conjugated polymers exhibit significant potential for use in gas sensors owing to their flexibility and straightforward preparation. However, the performance of organic gas sensors based on such materials is currently suboptimal owing to their poor charge‐transport properties and limited selectivity. To address this limitation, a novel strategy that involves blending a chemically modified metal–organic framework (MOF) material, UiO‐66, with a conjugated polymer is developed. The MOF porous material is chemically modified with polar nitrogen‐containing functional groups (amino and nitro groups) to create gas molecule adsorption sites. To evaluate the impact of these modifications on the sensing performance, experiments that combined the sensing performance with a density functional theory simulation are conducted. The findings reveal that gas sensors fabricated using an amine‐functionalized MOF blended with conjugated polymers exhibit significantly higher sensitivity than home polymer devices, the sensing performance of the UiO‐66‐NH2/P3HT blend film improved by a factor of two with a sensitivity of ≈2%/ppm and an LOD of 0.001 ppt. Additionally, these devices exhibit exclusive NO2‐sensing performance for other gases such as CO2 and SO2.

Background: Liver dysfunction is common during coronavirus disease 2019 (COVID-19), while its clinical impact and association with chronic hepatitis B (CHB) remain uncertain. We aimed to investigate liver dysfunction in COVID-19 patients and its impacts on those with/without CHB. Methods: We conducted a retrospective cohort study of COVID-19 patients at National Taiwan University Hospital, stratified according to hepatitis B surface antigen (HBsAg) serostatus, with demographics, laboratory data, and hospitalization course reviewed, and clinical outcomes compared through multivariable analyses. Results: We enrolled 109 COVID-19 patients unvaccinated against SARS-CoV-2 by August 2021. The HBsAg-positive group (n = 34) had significantly higher alanine aminotransferase (ALT) (26 vs. 16 U/L, P = 0.034), platelet (224 vs. 183 k/μL, P = 0.010) and longer hospitalizations (17 vs. 13 days, P = 0.012) compared with HBsAg-negative group (n = 75), while percentages of hepatitis (2-fold ALT elevation), oxygen supplementation, ventilators usage, COVID-specific treatment, intensive care unit (ICU) admission and mortality were comparable. Older age (odds ratio [OR]: 1.04, 95 % confidence interval [CI]: 1.00–1.08, P = 0.032) and higher aspartate aminotransferase (AST) (OR: 1.08, 95 % CI: 1.004–1.16, P = 0.038) were associated with oxygen supplementation according to multivariable analyses. Higher AST predicted ICU admission (OR: 1.11, 95 % CI: 1.03–1.19, P = 0.008). Oxygen usage (OR: 5.64, 95 % CI: 1.67–19.09, P = 0.005) and shock (OR: 5.12, 95 % CI: 1.14–22.91, P = 0.033) were associated with liver dysfunction. Conclusions: CHB patients had higher ALT levels and longer hospitalizations during COVID-19. Higher AST levels predict severe COVID-19 and ICU admission.

Abstract CircRNAs play an important role in various physiological and pathological biological processes. Despite their widespread involvement, the function of circRNAs in intermittent hypoxia (IH) remain incompletely understood. This study aims to clarify the molecular mechanism of it in IH. Differentially expressed circRNAs were identified by transcriptome sequencing analysis in intermittent hypoxia (IH) model. GO and KEGG enrichment analys were performed on the identified differentially expressed circRNAs. The circular characteristics of hsa_circ_0081065 in human umbilical vein endothelial cells (HUVECs) were detected by RT-qPCR. The sublocalization of hsa_circ_0081065 was examined by FISH. The effect of hsa_circ_0081065 on endothelial to mesenchymal transition (EndMT) was estimated by detecting the expression of EndMT related markers. Various techniques, including RNA-pull down, RIP, EMSA, dual-luciferase reporter assay and immunofluorescence staining were used to investigate the relationship among hsa_circ_0081065, miR-665 and HIF-1α. A total of 13,304 circRNAs were identified in HUVECs treatment with IH, among which 73 were differentially expressed, including 24 upregulated circRNAs and 49 downregulated circRNAs. Notably, hsa_circ_0081065 demonstrated a significantly upregulation. Hsa_circ_0081065 exhibited the circular characteristics of circRNA and was predominantly localized in the cytoplasm. Knockdown of hsa_circ_0081065 inhibited EndMT. Mechanically, we demonstrated that hsa_circ_0081065 acts as a sponge for miR-665 to up-regulate HIF-1α and exacerbate HIF-1α nuclear translocation in HUVECs. We have demonstrated that hsa_circ_0081065 is significantly upregulated in HUVECs treated with IH. Our findings indicate that hsa_circ_0081065 exacerbates IH-induced EndMT through the regulation of the miR-665/HIF-1α signal axis and facilitating HIF-1α nuclear translocation. These results provide a theoretical basis for considering of EndMT as a potential therapeutic target for OSAHS intervention.

Syncope is a transient loss of consciousness with rapid onset. The aims of the study were to systematically evaluate available machine learning (ML) algorithm for supporting syncope diagnosis to determine their performance compared to existing point scoring protocols. We systematically searched IEEE Xplore, Web of Science, and Elsevier for English articles (Jan 2011 - Sep 2021) on individuals aged five and above, employing ML algorithms in syncope detection with Head-up titl table test (HUTT)-monitored hemodynamic parameters and reported metrics. Extracted data encompassed subject count, age range, syncope protocols, ML type, hemodynamic parameters, and performance metrics. Of the 6301 studies initially identified, 10 studies, involving 1205 participants aged 5 to 82 years, met the inclusion criteria, and formed the basis for it. Selected studies must use ML algorithms in syncope detection with hemodynamic parameters recorded throughout HUTT. The overall ML algorithm performance achieved a sensitivity of 88.8% (95% CI: 79.4–96.1%), specificity of 81.5% (95% CI: 69.8–92.8%) and accuracy of 85.8% (95% CI: 78.6–92.8%). Machine learning improves syncope diagnosis compared to traditional scoring, requiring fewer parameters. Future enhancements with larger databases are anticipated. Integrating ML can curb needless admissions, refine diagnostics, and enhance the quality of life for syncope patients.

During mammalian oocyte meiosis, spindle migration and asymmetric cytokinesis are unique steps for the successful polar body extrusion. The asymmetry defects of oocytes will lead to the failure of fertilization and embryo implantation. In present study, we reported that an actin nucleating factor Formin-like 2 (FMNL2) played critical roles in the regulation of spindle migration and organelle distribution in mouse and porcine oocytes. Our results showed that FMNL2 mainly localized at the oocyte cortex and periphery of spindle. Depletion of FMNL2 led to the failure of polar body extrusion and large polar bodies in oocytes. Live-cell imaging revealed that the spindle failed to migrate to the oocyte cortex, which caused polar body formation defects, and this might be due to the decreased polymerization of cytoplasmic actin by FMNL2 depletion in the oocytes of both mice and pigs. Furthermore, mass spectrometry analysis indicated that FMNL2 was associated with mitochondria and endoplasmic reticulum (ER)-related proteins, and FMNL2 depletion disrupted the function and distribution of mitochondria and ER, showing with decreased mitochondrial membrane potential and the occurrence of ER stress. Microinjecting Fmnl2-EGFP mRNA into FMNL2-depleted oocytes significantly rescued these defects. Thus, our results indicate that FMNL2 is essential for the actin assembly, which further involves into meiotic spindle migration and ER/mitochondria functions in mammalian oocytes.

Objective Preoperative frailty and surgical waiting times are associated with the occurrence of adverse outcomes in patients with hip fractures. Specifically, we aimed to investigate the influence of frailty status and surgical timing on the risk of serious adverse events during hospitalization. Methods This study utilized an observational single cohort design and included patients aged ≥60 years with a primary diagnosis of hip fracture. Frailty was assessed using the chart-derived frailty index (CFI), which was calculated based on demographic and routine laboratory variables. The primary outcome of interest was the occurrence of in-hospital serious adverse events. A multivariate logistic regression model was utilized to examine the risk factors influencing outcomes. Results The study included 427 participants, with a mean age of 80.28 ± 8.13 years and 64.2% of whom were female. Patients with high CFI have more comorbidities ( P < .001), lower surgical rates ( P = .002), and delayed surgical times ( P = .033). A total of 239 patients (56.0%) experienced serious adverse events. The high CFI group had a significantly higher occurrence of serious adverse events compared to the low CFI group (73.4% vs 48.5%, P < .001). After adjusting for surgical timing and covariates, the multivariate logistic regression analysis revealed that high frailty significantly increased the risk for serious adverse events (OR = 2.47, 95% CI 1.398-4.412), infection (OR = 1.99, 95% CI 1.146-3.446), acute heart failure (OR = 3.37, 95% CI 1.607-7.045). However, the timing of surgery did not demonstrate any association with these outcomes. In addition, after adjusting for surgical factors, high CFI remains an independent risk factor for these complications. Conclusions Frailty serves as a reliable predictor of the probability of encountering severe adverse events while hospitalized for elderly individuals with hip fractures. This method has the potential to pinpoint particular modifiable factors that necessitate intervention, whereas the impact of surgical timing remains uncertain and necessitates additional research.

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.

BackgroundWe explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2 diabetes mellitus (T2DM).MethodsA 6-year follow-up study (2013-2019) enrolled T2DM patients aged >20 without DPN. Participants were classified into two groups: those below 65 years (non-elderly) and those 65 years or older (elderly). Biochemical measurements, including glycated hemoglobin (HbA1C), were recorded regularly. DPN was diagnosed using the Michigan Neuropathy Screening Instrument examination. The outcome was DPN occurrence in 2019.ResultsIn 552 enrollments (69% non-elderly), DPN occurred in 8.4% non-elderly and 24.0% elderly patients. A higher initial HbA1C level was significantly linked with a higher risk of future DPN in the non-elderly group (adjusted odds ratio [AOR] 1.46, 95% CI 1.13–1.89, p=0.004). In comparison, HbA1c at the end of the study period was not associated with DPN in the non-elderly group (AOR 1.17, 95% CI 0.72–1.90, p=0.526). In the elderly group, no statistical relationship was found between HbA1C levels and DPN, either in 2013 or in 2019.ConclusionSuboptimal glycemic control at baseline, rather than at the end of the study period, predicts an increased risk of future DPN in individuals with T2DM under age 65. This correlation is not seen in elderly patients. Therefore, we recommend implementing enhanced glycemic control early in middle-aged T2DM patients and propose individualized therapeutic strategies for diabetes in different age groups.

BackgroundLimited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms.MethodsPD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson’s Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains.ResultsA total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores (p = 0.003, p = 0.012, and p = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p

Abstract Background With the continuous discovery of new borderline thyroid lesions and benign and malignant “gray areas”, coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. Methods In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. Results Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P

Male infertility affects millions of men worldwide and is increasing in prevalence, with asthenozoospermia (AS) and oligoasthenozoospermia (OA) being the most frequent causes, and current treatments are limited. A previous research reported that Linggui Yangyuan paste (LGYY) enhanced sperm viability and motility, but there is a lack of multicenter, rigorous, randomized and controlled studies on its efficacy. Wuzi Yanzong oral solution (WZYZ), a traditional Chinese herbal formula, is one of the most important and first-line drugs for AS and OA in China. We designed a direct comparison of LGYY’s effectiveness and safety against WZYZ in treating male infertility, specifically AS and OA. We propose a multicenter, double-blind, double-dummy, randomized controlled trial, which is planned to recruit 162 participants with AS or OA from five centers and will randomize them into two groups, whereby the treatment group will receive intervention with LGYY and WZYZ mimetics, while the control group will receive intervention with WZYZ and LGYY mimetics. The medications will be administered twice daily for 12 weeks, followed by a 12-week follow-up. The primary outcome will be total progressive motile sperm count (TPMSC), and the secondary outcomes will be semen parameters, including semen volume, sperm concentration, total sperm count, progressive motility (PR), PR + nonprogressive motility (NP), Chinese Medicine Symptoms Score (CMSS), spouse pregnancy rate and time to pregnancy. The safety outcomes will be based on the results of routine blood and urine tests, liver and kidney function tests and electrocardiography. Overall, this study aims to provide valuable insights into the potential efficacy and safety of LGYY compared to WZYZ for male infertility (AS or OA), which could guide clinicians to an alternative drug approach to treat patients with AS or OA. This clinical trial is registered at ClinicalTrials.org under the identifier NCT05792813.

Abstract Purpose Tension pneumomediastinum is a rare and dangerous complication in children that can be fatal, and timely detection and treatment are critical. The aim of this study was to evaluate the safety and feasibility of computed tomography (CT) imaging-guided parasternal approach drainage for tension pneumomediastinum in children. Methods From June 2018 to February 2023, we consecutively enrolled 19 children with tension pneumomediastinum in our institution. A pigtail catheter was inserted into the anterior mediastinum by a CT imaging-guided parasternal approach. The catheter was connected to a negative-pressure water seal bottle to drain the pneumomediastinum. Clinical data and outcomes were summarized. Results The mean age was 3.1 ± 3.4 years, the mean weight was 15 ± 9.1 kg, the mean procedure time was 11.8 ± 2.4 min, and the drainage time was 6.7 ± 3.4 days. No major complications were identified, such as haemothorax, catheter displacement, or mediastinal infection. Effective drainage was obtained in all patients as assessed by comparing images and ventilatory parameters, and no additional surgical treatment was needed. There was no recurrence during the follow-up, which was more than 2 months. In our data, two children with COVID-19 were discharged from the hospital after effective drainage and other clinical treatment. Conclusion CT-guided parasternal approach drainage is safe, minimally invasive, and effective for children with tension pneumomediastinum.

Abstract Background Lung cancer is the most common and deadliest cancer worldwide, and approximately 90% of all lung cancer deaths are caused by tumor metastasis. Tumor-derived exosomes could potentially promote tumor metastasis through the delivery of metastasis-related molecules. However, the function and underlying mechanism of exosomal long noncoding RNA (lncRNA) in lung cancer metastasis remain largely unclear. Methods Cell exosomes were purified from conditioned media by differential ultracentrifugation and observed using transmission electron microscopy, and the size distributions were determined by nanoparticle tracking analysis. Exosomal lncRNA sequencing (lncRNA-seq) was used to identify long noncoding RNAs. Cell migration and invasion were determined by wound-healing assays, two-chamber transwell invasion assays and cell mobility tracking. Mice orthotopically and subcutaneously xenografted with human cancer cells were used to evaluate tumor metastasis in vivo. Western blot, qRT‒PCR, RNA-seq, and dual-luciferase reporter assays were performed to investigate the potential mechanism. The level of exosomal lncRNA in plasma was examined by qRT‒PCR. MS2-tagged RNA affinity purification (MS2-TRAP) assays were performed to verify lncRNA-bound miRNAs. Results Exosomes derived from highly metastatic lung cancer cells promoted the migration and invasion of lung cancer cells with low metastatic potential. Using lncRNA-seq, we found that a novel lncRNA, lnc-MLETA1, was upregulated in highly metastatic cells and their secreted exosomes. Overexpression of lnc-MLETA1 augmented cell migration and invasion of lung cancer. Conversely, knockdown of lnc-MLETA1 attenuated the motility and metastasis of lung cancer cells. Interestingly, exosome-transmitted lnc-MLETA1 promoted cell motility and metastasis of lung cancer. Reciprocally, targeting lnc-MLETA1 with an LNA suppressed exosome-induced lung cancer cell motility. Mechanistically, lnc-MLETA1 regulated the expression of EGFR and IGF1R by sponging miR-186-5p and miR-497-5p to facilitate cell motility. The clinical datasets revealed that lnc-MLETA1 is upregulated in tumor tissues and predicts survival in lung cancer patients. Importantly, the levels of exosomal lnc-MLETA1 in plasma were positively correlated with metastasis in lung cancer patients. Conclusions This study identifies lnc-MLETA1 as a critical exosomal lncRNA that mediates crosstalk in lung cancer cells to promote cancer metastasis and may serve as a prognostic biomarker and potential therapeutic target for lung cancer diagnosis and treatment.

Abstract Background The safety and efficacy of 17-gauge needles used in CT-guided percutaneous cryoablation for lung nodules were explored in this study. The purpose of the study was to compare the findings with earlier research and multi-center clinical trials that used various needle sizes. Methods Between 2016 and 2020, a retrospective study was conducted with approval from the institutional review board. A total of 41 patients were enrolled, and 71 lung nodules were treated in 63 cryoablation procedures using local anesthesia. Complication rates were recorded, and overall survival rates as well as tumor progression-free rates were calculated using the Kaplan-Meier method. Results Self-limited hemoptysis was caused by 12.9% of the procedures, and drainage was required for pneumothoraces resulting from 11.3% of them. The overall survival rates at one, two, three, and four years were 97%, 94%, 82%, and 67%, respectively. The tumor progression-free rates at one, two, three, and four years were 86.2%, 77%, 74%, and 65%, respectively. Conclusion Cryoablation for lung nodules using 17-Gauge needles can achieve similar rates of survival and tumor control rates, similar or even lower complication rates as compared with other studies and multi-center trials using mixed sized needles.

Assisted reproduction technology (ART) procedures are often impacted by post-ovulatory aging (POA), which can lead to reduced fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte (A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte (A_vitro) were intersected to explore the co-effects of POA. It was found that “organelles”, especially “mitochondria”, were significantly enriched Gene Ontology (GO) terms. The expression of genes related to the “electron transport chain” and “cell redox homeostasis” pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. Weighted correlation network analysis was carried out to explore gene expression modules specific to A_vivo. Trait–module association analysis showed that the red modules were most associated with in vivo aging. There are 959 genes in the red module, mainly enriched in “RNA binding”, “mRNA metabolic process”, etc., as well as in GO terms, and “spliceosome” and “nucleotide excision repair” pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. Subsequently, the functions of DDX18 and DNAJC7 were verified by knocking down their expression at the germinal vesicle (GV) and Metaphase II (MII) stages, respectively. Knockdown at the GV stage caused cell cycle disorders and increase the rate of abnormal spindle. Knockdown at the MII stage resulted in the inefficiency of the antioxidant melatonin, increasing the level of intracellular oxidative stress, and in mitochondrial dysfunction. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study provides a better understanding of the detailed mechanism of POA and potential strategies for improving the success rates of assisted reproductive technologies in pigs and other mammalian species.

BackgroundOlfactory dysfunction in Parkinson’s disease (PD) is associated with more severe phenotypes, but trajectories of cognitive function, disease severity, and subdomains of quality-of-life measurements in patients with distinct olfactory profiles remain underexplored.ObjectiveTo analyze the influence of olfaction on trajectories of clinical parameters in patients with PD.DesignRetrospective cohort study.SubjectsFrom October 2016 to May 2021, the study tracked 58 participants over 3 years. Participants completed follow-up assessments using tools including the Chinese version of the University of Pennsylvania’s Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, and the Chinese translation of the 39-item Parkinson’s Disease Questionnaire (PDQ-39).MethodsParticipants were divided into anosmia (UPSIT < 19) and non-anosmia (UPSIT ≥ 19) groups based on initial scores. Generalized estimating equations and repeated measures correlations were used to examine longitudinal associations and correlations between olfaction and clinical parameters.ResultsDivergent cognitive trajectories were observed between groups. The anosmia group exhibited a faster cognitive decline (adjusted B [beta coefficient] = −1.8, p = 0.012) according to the interaction effect of olfaction and time on the MoCA score. The anosmia group exhibited no longitudinal correlation between cognition and olfactory function but showed correlations with age (rrm [coefficient of repeated measures correlation] = −0.464, p = 0.004) and disease duration (rrm = −0.457, p = 0.005). The non-anosmia group’s UPSIT scores decreased over time (B = −2.3, p = 0.005) alongside a significant correlation with motor function (rrm = −0.479, p = 0.006).ConclusionThe anosmia group’s accelerated cognitive decline correlated with age and disease duration, but not olfactory function, suggesting a poor cognitive outcome in this population despite the lack of longitudinal correlation between cognition and olfaction. The non-anosmia group exhibited progressive olfactory degradation and notable correlations between motor function and UPSIT scores, implying pathological accumulation in the olfactory structure and basal ganglia.

BackgroundWe explored the characteristics of single-cell differentiation data in glioblastoma and established prognostic markers based on CRYAB to predict the prognosis of glioblastoma patients. Aberrant expression of CRYAB is associated with invasive behavior in various tumors, including glioblastoma. However, the specific role and mechanisms of CRYAB in glioblastoma are still unclear.MethodsWe assessed RNA-seq and microarray data from TCGA and GEO databases, combined with scRNA-seq data on glioma patients from GEO. Utilizing the Seurat R package, we identified distinct survival-related gene clusters in the scRNA-seq data. Prognostic pivotal genes were discovered through single-factor Cox analysis, and a prognostic model was established using LASSO and stepwise regression algorithms. Moreover, we investigated the predictive potential of these genes in the immune microenvironment and their applicability in immunotherapy. Finally, in vitro experiments confirmed the functional significance of the high-risk gene CRYAB.ResultsBy analyzing the ScRNA-seq data, we identified 28 cell clusters representing seven cell types. After dimensionality reduction and clustering analysis, we obtained four subpopulations within the oligodendrocyte lineage based on their differentiation trajectory. Using CRYAB as a marker gene for the terminal-stage subpopulation, we found that its expression was associated with poor prognosis. In vitro experiments demonstrated that knocking out CRYAB in U87 and LN229 cells reduced cell viability, proliferation, and invasiveness.ConclusionThe risk model based on CRYAB holds promise in accurately predicting glioblastoma. A comprehensive study of the specific mechanisms of CRYAB in glioblastoma would contribute to understanding its response to immunotherapy. Targeting the CRYAB gene may be beneficial for glioblastoma patients.

Background & Aims: Risk scores have been designed to predict the development of hepatocellular carcinoma (HCC) in treatment-naive patients with chronic hepatitis B (CHB). However, little is known about their predictive accuracy in HBeAg-negative patients in the grey zone (GZ). We aimed to develop a HBcrAg-based HCC risk score and explore whether it outperforms other risk scores in GZ patients. Methods: Two retrospective cohorts of HBeAg-negative patients with American Association for the Study of Liver Diseases-defined GZ were established for derivation and validation (Taiwanese, N = 911; Japanese, N = 806). All of them were non-cirrhotic at baseline and remained treatment-naive during the follow-up. The primary endpoint was HCC development. Results: In a median follow-up period of 15.5 years, 85 patients developed HCC in the derivation cohort. We found that age, sex, alanine aminotransferase, platelet count, and HBcrAg, but not HBV DNA levels, were independent predictors and a 20-point GZ-HCC score was developed accordingly. The 10-year and 15-year area under the ROC curve (AUROC) ranged from 0.83 to 0.86, which outperformed the HBV DNA-based HCC risk scores, including REACH-B and GAG-HCC scores (AUROC ranging from 0.66 to 0.74). The better performance was also validated in EASL- and Asian Pacific Association for the Study of the Liver-defined GZ patients. These findings remained consistent in the validation cohort. Finally, the low-risk and high-risk GZ patients (stratified by a score of 8) had an HCC risk close to inactive CHB and immune-active CHB patients, respectively, in both cohorts. Conclusions: The HBcrAg-based GZ-HCC score predicts HCC better than other HBV DNA-based risk scores in GZ patients who are HBeAg-negative patients, which may help optimise their clinical management. Impact and implications: We have developed a risk score based on HBcrAg, which has shown better predictive ability for HCC compared with other risk scores based on HBV DNA. Using a score of 8, GZ patients can be classified into low- and high-risk groups, which can guide follow up and early treatment, respectively. This validated risk score is a valuable tool for optimising the management of GZ patients who are HBeAg-negative.