Single immunization of non-adjuvanted recombinant TTFC-mi3 nanoparticle vaccine elicited a rapid and potent protective immunity against tetanus.

The conventional inactivated tetanus toxin plays an instrumental role in preventing tetanus. Nevertheless, the challenges associated with its production process, the potential for adverse reactions, and reduced effectiveness in vulnerable populations such as neonates and the elderly rise the need for a novel tetanus toxin vaccine. Recombinant subunit vaccine offer a viable solution, and the tetanus toxin fragment C (TTFC) is emerging as a promising candidate. In this study, through spontaneous isopeptide bond formation we conjugated the recombinant TTFC to self-assembled mi3 nanoparticle, which derived from an optimized KDPG aldolase, and generated the TTFC-mi3 protein nanoparticle vaccine. We found that TTFC-mi3 is stable, uniform spherical nanoparticles. Comparing with the free TTFC alone, TTFC-mi3 enhances the uptake and subsequent activation of dendric cells (DCs). In addition, a single dose of adjuvant-free TTFC-mi3 elicited a more rapid and potent protective immunity in mice. Moreover, TTFC-mi3 is of favorable safety in vitro and in vivo. Our findings indicate that TTFC-mi3 is a rapid-response, non-aluminum-adjuvanted vaccine against tetanus.

Yangonin, one of the kavalactones isolated from Piper methysticum G. Forst, acts through cannabinoid 1 (CB1) receptors to induce an intrathecal anti-hyperalgesia.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper methysticum G. Forst (Piperaceae) is traditionally consumed in Polynesian culture. The roots are used to produce an entheogenic drink and traditional medicine with sedative and anxiolytic properties. There is also evidence that it functions as a pain reliever. Kavalactones, its main active ingredients, exhibit psychoactive effects on the central nervous system. However, the active ingredients and pharmacological mechanisms underlying the analgesic effect of kavalactones are unclear. AIM OF THE STUDY: This study investigated the effects of kavain and yangonin on nociception, inflammatory hyperalgesia, and neuropathic mechanical allodynia at the spinal level. MATERIALS AND METHODS: Male Sprague-Dawley rats were administered kavain and yangonin (27.14 and 19.36 nmol/rat) via intrathecal injection. Tail-flick tests were performed to evaluate the anti-nociceptive properties. The efficacy of kavain and yangonin on inflammatory hyperalgesia was examined using a plantar test in rats with carrageenan-induced paw inflammation. The von Frey test was used to assess mechanical allodynia induced by partial sciatic nerve ligation. RESULTS: Intrathecal injection of yangonin demonstrated a relatively potent anti-nociceptive effect and attenuated carrageenan-induced hyperalgesia. These effects were completely reversed by the co-administration of PF 514273, a cannabinoid 1 (CB1) receptor antagonist. However, yangonin did not affect mechanical allodynia at the spinal level. Kavain, another abundant kavalactone, did not affect nociception, hyperalgesia, or mechanical allodynia at the spinal level. CONCLUSIONS: Overall, our study demonstrated that yangonin exerts anti-nociception and anti-inflammatory hyperalgesia effects via CB1 receptors at the spinal level. We identified a single kavalactone, yangonin, extracted from kava as a promising treatment for pain.

Successful Treatment Without Using Dantrolene Sodium on a Child Occurring Malignant Hyperthermia During Induction of General Anesthesia: A Case Report.

Malignant hyperthermia (MH) is a fatal hyperthermia with a high mortality, which usually occurs during induction of general anesthesia. Dantrolene sodium is a wonder drug currently used for treating malignant hyperthermia. However, preparing, storing, and maintaining dantrolene sodium are crucially expensive, thus making it financially unsatisfactory and difficult for clinicians to acquire in time. Monitoring patients' condition closely and intervening promptly when early signs of malignant hyperthermia occur can effectively prevent the condition from worsening and win over time for the arrival of dantraline sodium. This article is to report a case in which we successfully rescued a child occurring malignant hyperthermia without using dantrolene sodium.

Dose dense doxorubicin plus cyclophosphamide in a modified KEYNOTE522 regimen for triple negative breast cancer.

The KEYNOTE-522 (KN522) regimen for neoadjuvant treatment of triple negative breast cancer (TNBC) utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has demonstrated superior overall survival (OS) compared to q3week AC in anthracycline and taxane-based regimens. We performed a retrospective analysis assessing the use of ddAC in KN522 and the impact of sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab on multiple outcomes. 128 patients with TNBC were included. Overall pathologic complete response (pCR) rate of 56%. Sequencing of ddAC vs CbT first showed no difference in pCR rate (ddAC 55% vs. CbT 58%, p = 0.77). However, ddAC first compared to CbT first correlated with a significant increase in the incidence of overall treatment delays (ddAC 70% vs. CbT 51%, p = 0.03), with cytopenias most frequent (ddAC 59% vs. CbT 31%, p = 0.001). ddAC in a modified KN522 regimen is safe, tolerable, and effective. Efficacy is comparable regardless of chemotherapy sequencing, but ddAC first is significantly associated with higher rates of treatment delays and cytopenias.

A case report of pancreatic mucoepidermoid carcinoma responded to gemcitabine and paclitaxel.

Mucoepidermoid carcinoma (MEC) typically manifests in the salivary glands, but occurrences in the pancreatic gland are exceedingly rare. Surgical resection proves effective; however, pancreatic MEC is prone to metastasis, and lacking a standardized postoperative treatment. We discussed the experience of a 51-year-old female patient with pancreatic MEC who received paclitaxel and gemcitabine as postoperative care. Within a predetermined amount of time, this regimen successfully stopped the spread of metastatic tumors and returned tumor markers to normal. A Stable Disease status was achieved within 6 months after chemotherapy. In summary, gemcitabine and paclitaxel display efficacy in treating pancreatic MEC.

High-Grade Malignant Peripheral Nerve Sheath Tumor Arising From Common Peroneal Nerve Neurofibroma.

This article presents a case report of a 45-year-old male with neurofibromatosis type I (NF1) who developed a high-grade malignant peripheral nerve sheath tumor (MPNST) originating from a neurofibroma within the common peroneal nerve over popliteal fossa. MPNSTs are aggressive tumors associated with NF1, causing significant mortality. The patient underwent tumor resection surgery and received postoperative radiation therapy. Follow-up examinations showed no impairment of motor function and no tumor recurrence after regular MRI evaluation for four years. This article explores the challenges of distinguishing benign neurofibromas from malignant MPNST via MRI image and biopsy, and achieving a balance between tumor excision and preserving nerve functionality during surgical treatment. However, caution is warranted due to the risk of recurrence.

Endoscopic Ultrasound-Guided Fine Needle Aspiration has High Diagnostic Value in the Diagnosis of Solid Pancreatic Lesions.

Objective: To analyze the potential factors influencing the diagnostic capability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and provide medication treatment recommendations for patients with pancreatic solid mass lesions. Methods: A retrospective analysis was conducted on clinical data of 92 patients with pancreatic solid mass lesions who underwent EUS-FNA examination after detection by imaging studies. The diagnostic effectiveness of EUS-FNA was evaluated based on cytological or histological examination results. Logistic regression analysis was subsequently performed to analyze the potential factors influencing the diagnostic capability of EUS-FNA in patients with pancreatic solid mass lesions. Results: EUS-FNA was successfully performed in all 92 patients, with a puncture success rate of 100.00%. Only one patient experienced transient hyperamylasemia, which resolved with conservative treatment. No other serious complications were observed. Among the 92 patients, 70 patients obtained a definite diagnosis after EUS-FNA (Group A), while 22 patients did not achieve a definite diagnosis (Group B) after the procedure. Univariate analysis showed that lesion size, dilation of the pancreatic duct or bile duct, negative pressure, and suction method were significantly different between Group A and Group B (P < .05). Multivariate logistic regression analysis revealed that lesion size, dilation of the pancreatic duct or bile duct, negative pressure, and suction method were potential factors influencing the diagnostic ability of EUS-FNA in patients with solid pancreatic lesions (P < .05). Conclusion: EUS-FNA has a high diagnostic value in the evaluation of solid pancreatic lesions. Lesion size, dilation of the pancreatic duct or bile duct, negative pressure, and suction method are potential factors influencing the diagnostic ability of EUS-FNA in patients with solid pancreatic lesions. In terms of medical treatment, specific treatment methods and drug choices should be based on a comprehensive evaluation of the nature of the patient's lesions and the severity of the condition.

Multiscale brain age prediction reveals region-specific accelerated brain aging in Parkinson's disease.

Brain biological age, which measures the aging process in the brain using neuroimaging data, has been used to assess advanced brain aging in neurodegenerative diseases, including Parkinson disease (PD). However, assuming that whole brain degeneration is uniform may not be sufficient for assessing the complex neurodegenerative processes in PD. In this study we constructed a multiscale brain age prediction models based on structural MRI of 1240 healthy participants. To assess the brain aging patterns using the brain age prediction model, 93 PD patients and 91 healthy controls matching for sex and age were included. We found increased global and regional brain age in PD patients. The advanced aging regions were predominantly noted in the frontal and temporal cortices, limbic system, basal ganglia, thalamus, and cerebellum. Furthermore, region-level rather than global brain age in PD patients was associated with disease severity. Our multiscale brain age prediction model could aid in the development of objective image-based biomarkers to detect advanced brain aging in neurodegenerative diseases.

Investigating a novel surrogate indicator of adipose accumulation in relation to erectile dysfunction.

INTRODUCTION: Although previous studies have linked obesity and erectile dysfunction, the novel surrogate indicators of adipose accumulation are more essential and dependable factors to consider. Therefore, the primary objective of the current investigation was to examine and clarify the association between metabolic score for visceral fat (METS-VF) and erectile dysfunction. METHODS: Firstly, multivariate logistic regression analysis, smoothed curve fitting, and threshold effect analysis were employed to investigate the association between METS-VF and erectile dysfunction. Mediation analysis was also performed to evaluate the mediating role of homocysteine and inflammation. After that, subgroup analysis was carried out to examine the stability of the correlation of METS-VF with erectile dysfunction in various population settings. Furthermore, the area under the receiver operating characteristic (ROC) curve and eXtreme Gradient Boosting (XGBoost) algorithm were utilized to assess the capability of identifying METS-VF in comparison to the other four obesity-related indicators in identifying erectile dysfunction. RESULTS: After adjusting for all confounding factors, METS-VF was strongly and favourablely correlated with erectile dysfunction. With each additional unit rise in METS-VF, the prevalence of erectile dysfunction increased by 141%. A J-shaped relationship between METS-VF and erectile dysfunction was discovered through smoothed curve fitting. Marital status, physical activity, and smoking status can potentially modify this association. This finding of the ROC curve suggests that METS-VF had a powerful identifying capacity for erectile dysfunction (AUC = 0.7351). Homocysteine and inflammation mediated 4.24% and 2.81%, respectively. CONCLUSION: The findings of the current investigation suggest that METS-VF can be considered a dependable identifying indicator of erectile dysfunction.

Chemical composition and bioactivity variability of two-step extracts derived from traditional and "QiNan" agarwood (Aquilaria spp.).

One of the primary applications for agarwood lies in the extracts, instead, there are obvious differences in the demands for agarwood components with different application fields. To obtain the rough separation and clarify each part's activity, four extracts of essential oil, hydrolat, extractum, and ethanol precipitation from traditional agarwood (TraA) and "Qinan" agarwood (QinA) were obtained by steam-solvent multistage extraction and ethanol precipitation. We investigated the chemistry and biological activity of multistage extracts using gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), and in vitro activity testing. The results demonstrated that two kinds of agarwood essential oils contained mainly sesquiterpenoids, yet the sesquiterpene species were remarkably diverse in two kinds of agarwood essential oils. Then, the TraA and QinA hydrolat, all predominantly aromatic and sesquiterpene, but with differences from the essential oil ingredients. Additionally, the extractum chiefly contained chromones and the ethanol precipitation method worked well to separate the impurities in the TraA extract, however, it was ineffective for the QinA extract. Ultimately, essential oils and extractums all have antioxidant properties, with extractums outperforming essential oils. Moreover, both extractums and essential oils exhibited excellent broad-spectrum antimicrobial activity and anti-inflammatory activity. The findings pointed to the feasibility of separating the primary components from TraA and QinA using a multi-stage extraction technique, providing a scientific basis for the efficient utilization of all components of agarwood, as well as the functional product development and differentiated utilization of extract products in incense, fragrance, perfume, and daily chemicals.

A study on construction of a prognosis model for liver cancer based on analgesic targets and screening therapeutic drugs.

BACKGROUND: Liver cancer is one of the most malignant liver diseases in the world, and the 5-year survival rate of such patients is low. Analgesics are often used to cure pain prevalent in liver cancer. The expression changes and clinical significance of the analgesic targets (ATs) in liver cancer have not been deeply understood. OBJECTIVE: The purpose of this study is to clarify the expression pattern of ATs gene in liver cancer and its clinical significance. Through the comprehensive analysis of transcriptome data and clinical parameters, the prognosis model related to ATs gene is established, and the drug information sensitive to ATs is mined. METHODS: The study primarily utilized transcriptomic data and clinical information from liver cancer patients sourced from The Cancer Genome Atlas (TCGA) database. These data were employed to analyze the expression of ATs, conduct survival analysis, gene set variation analysis (GSVA), immune cell infiltration analysis, establish a prognostic model, and perform other bioinformatic analyses. Additionally, data from liver cancer patients in the International Cancer Genome Consortium (ICGC) were utilized to validate the accuracy of the model. Furthermore, the impact of analgesics on key genes in the prognostic model was assessed using data from the Comparative Toxicogenomics Database (CTD). RESULTS: The study investigated the differential expression of 58 ATs genes in liver cancer compared to normal tissues. Patients were stratified based on ATs expression, revealing varied survival outcomes. Functional enrichment analysis highlighted distinctions in spindle organization, centrosome, and spindle microtubule functions. Prognostic modeling identified low TP53 expression as protective, while elevated CCNA2, NEU1, and HTR2C levels posed risks. Commonly used analgesics, including acetaminophen and others, were found to influence the expression of these genes. These findings provide insights into potential therapeutic strategies for liver cancer and shed light on the molecular mechanisms underlying its progression. CONCLUSIONS: The collective analysis of gene signatures associated with ATs suggests their potential as prognostic predictors in hepatocellular carcinoma patients. These findings not only offer insights into cancer therapy but also provide novel avenues for the development of indications for analgesics.

DMGM: deformable-mechanism based cervical cancer staging via MRI multi-sequence.

Objective.This study aims to leverage a deep learning approach, specifically a deformable convolutional layer, for staging cervical cancer using multi-sequence MRI images. This is in response to the challenges doctors face in simultaneously identifying multiple sequences, a task that computer-aided diagnosis systems can potentially improve due to their vast information storage capabilities.Approach.To address the challenge of limited sample sizes, we introduce a sequence enhancement strategy to diversify samples and mitigate overfitting. We propose a novel deformable ConvLSTM module that integrates a deformable mechanism with ConvLSTM, enabling the model to adapt to data with varying structures. Furthermore, we introduce the deformable multi-sequence guidance model (DMGM) as an auxiliary diagnostic tool for cervical cancer staging.Main results.Through extensive testing, including comparative and ablation studies, we validate the effectiveness of the deformable ConvLSTM module and the DMGM. Our findings highlight the model's ability to adapt to the deformation mechanism and address the challenges in cervical cancer tumor staging, thereby overcoming the overfitting issue and ensuring the synchronization of asynchronous scan sequences. The research also utilized the multi-modal data from BraTS 2019 as an external test dataset to validate the effectiveness of the proposed methodology presented in this study.Significance.The DMGM represents the first deep learning model to analyze multiple MRI sequences for cervical cancer, demonstrating strong generalization capabilities and effective staging in small dataset scenarios. This has significant implications for both deep learning applications and medical diagnostics. The source code will be made available subsequently.

Successful bilateral lung transplantation in a five-year-old child with pulmonary interstitial fibrosis caused by an ABCA3 gene mutation.

The ATP-binding cassette subfamily A member 3 (ABCA3) protein plays a fundamental role in surfactant homeostasis. Most children with ABCA3 gene mutations develop pulmonary interstitial fibrosis leading to the development of interstitial lung disease. Since traditional medicine does not offer effective therapy, the best option is lung transplantations, especially bilateral lung transplantations. We are reporting the case of a successful bilateral lung transplantation in a five-year-old child with pulmonary interstitial fibrosis caused by ABCA3 gene mutations. This successful transplantation enabled the patient to get rid of chronic cough and tachypnea.

UbNiRF: A Hybrid Framework Based on Null Importances and Random Forest that Combines Multiple Features to Predict Ubiquitination Sites in Arabidopsis thaliana and Homo sapiens.

BACKGROUND: Ubiquitination is a crucial post-translational modification of proteins that regulates diverse cellular functions. Accurate identification of ubiquitination sites in proteins is vital for understanding fundamental biological mechanisms, such as cell cycle and DNA repair. Conventional experimental approaches are resource-intensive, whereas machine learning offers a cost-effective means of accurately identifying ubiquitination sites. The prediction of ubiquitination sites is species-specific, with many existing models being tailored for Arabidopsis thaliana (A. thaliana) and Homo sapiens (H. sapiens). However, these models have shortcomings in sequence window selection and feature extraction, leading to suboptimal performance. METHODS: This study initially employed the chi-square test to determine the optimal sequence window. Subsequently, a combination of six features was assessed: Binary Encoding (BE), Composition of K-Spaced Amino Acid Pair (CKSAAP), Enhanced Amino Acid Composition (EAAC), Position Weight Matrix (PWM), 531 Properties of Amino Acids (AA531), and Position-Specific Scoring Matrix (PSSM). Comparative evaluation involved three feature selection methods: Minimum Redundancy-Maximum Relevance (mRMR), Elastic net, and Null importances. Alongside these were four classifiers: Support Vector Machine (SVM), Decision Tree (DT), Random Forest (RF), and Extreme Gradient Boosting (XGBoost). The Null importances combined with the RF model exhibited superior predictive performance, and was denoted as UbNiRF (A. thaliana: ArUbNiRF; H. sapiens: HoUbNiRF). RESULTS: A comprehensive assessment indicated that UbNiRF is superior to existing prediction tools across five performance metrics. It notably excelled in the Matthews Correlation Coefficient (MCC), with values of 0.827 for the A. thaliana dataset and 0.781 for the H. sapiens dataset. Feature analysis underscores the significance of integrating six features and demonstrates their critical role in enhancing model performance. CONCLUSIONS: UbNiRF is a valuable predictive tool for identifying ubiquitination sites in both A. thaliana and H. sapiens. Its robust performance and species-specific discovery capabilities make it extremely useful for elucidating biological processes and disease mechanisms associated with ubiquitination.

CAVE: Cerebral artery-vein segmentation in digital subtraction angiography.

Cerebral X-ray digital subtraction angiography (DSA) is a widely used imaging technique in patients with neurovascular disease, allowing for vessel and flow visualization with high spatio-temporal resolution. Automatic artery-vein segmentation in DSA plays a fundamental role in vascular analysis with quantitative biomarker extraction, facilitating a wide range of clinical applications. The widely adopted U-Net applied on static DSA frames often struggles with disentangling vessels from subtraction artifacts. Further, it falls short in effectively separating arteries and veins as it disregards the temporal perspectives inherent in DSA. To address these limitations, we propose to simultaneously leverage spatial vasculature and temporal cerebral flow characteristics to segment arteries and veins in DSA. The proposed network, coined CAVE, encodes a 2D+time DSA series using spatial modules, aggregates all the features using temporal modules, and decodes it into 2D segmentation maps. On a large multi-center clinical dataset, CAVE achieves a vessel segmentation Dice of 0.84 (±0.04) and an artery-vein segmentation Dice of 0.79 (±0.06). CAVE surpasses traditional Frangi-based k-means clustering (P < 0.001) and U-Net (P < 0.001) by a significant margin, demonstrating the advantages of harvesting spatio-temporal features. This study represents the first investigation into automatic artery-vein segmentation in DSA using deep learning. The code is publicly available at https://github.com/RuishengSu/CAVE_DSA.

Mitigating treatment failure of pulmonary pre-extensively drug-resistant tuberculosis: The role of new and repurposed drugs.

BACKGROUND: Pre-extensively drug-resistant tuberculosis (pre-XDR-TB), defined as multidrug-resistant TB (MDR-TB) with additional resistance to any fluoroquinolone (FQ) is difficult to treat. We assessed whether the use of new or repurposed drugs (bedaquiline, delamanid, linezolid, carbapenem, clofazimine, pretomanid) mitigated treatment failure of pre-XDR-TB. METHODS: MDR-TB patients managed in the Taiwan MDR-TB consortium between July 2009-December 2019 were eligible. Treatment outcomes at 30 months were assessed. Logistic regression models were constructed to investigate factors associated with treatment outcomes. RESULTS: 109 patients with FQ-resistant MDR-TB and 218 patients with FQ-susceptible MDR-TB were included. 60 (55.1%) patients with FQ-resistant MDR-TB and 63 (28.9%) patients with FQ-susceptible MDR-TB have been treated with new or repurposed drugs (p < 0.01). Of the 218 patients with FQ-susceptible MDR-TB, 187 (85.8%) had treatment success, 30 (13.8%) died, no treatment failure, and 1 (0.5%) was loss-to-follow-up; of the 109 patients with FQ-resistant MDR-TB, 78 (71.6%) had treatment success, 21 (19.3%) died, 9 (8.3%) had treatment failure, and 1 (0.9%) was loss-to-follow-up (p < 0.01). The use of new or repurposed drugs was not associated with treatment outcomes among patients with FQ-susceptible MDR-TB. No patients with FQ-resistant MDR-TB treated with ≥2 new or repurposed drugs within 6 months of treatment initiation had treatment failure (p = 0.03). Patients with FQ-resistant MDR-TB treated with 1 new or repurposed drugs was more likely to have treatment failure as compared with patients not treated with new or repurposed drugs (adjOR 7.06, 95% CI 1.72-29.06). CONCLUSIONS: Proper use of new or repurposed anti-TB drugs can mitigate treatment failure in FQ-resistant MDR-TB.

Impact of exercise on chemotherapy-induced peripheral neuropathy in survivors with post-treatment primary breast cancer.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of neurotoxic chemotherapy. Exercise activates neuromuscular function and may improve CIPN. We examined the association between exercise and CIPN symptoms in breast cancer survivors. METHODS: In a retrospective cross-sectional study, we included patients completing a survey assessing exercise exposure and neuropathy symptoms in a tertiary cancer center survivorship clinic. We evaluated exercise duration and intensity using a standardized questionnaire quantified in metabolic equivalent tasks (MET-h/wk). We defined exercisers as patients meeting the National Physical Activity Guidelines' criteria. We used multivariable logistic regressions to examine the relationship between exercise and CIPN and if this differed as a function of chemotherapy regimen adjusting for age, gender, and race. RESULTS: We identified 5444 breast cancer survivors post-chemotherapy (median age 62 years (interquartile range [IQR]: 55, 71); median 4.7 years post-chemotherapy (IQR: 3.3, 7.6)) from 2017 to 2022. CIPN overall prevalence was 34% (95% confidence interval [CI]: 33%, 36%), 33% for non-taxane, and 37% for taxane-based chemotherapy. CIPN prevalence was 28% (95% CI: 26%, 30%) among exercisers and 38% (95% CI: 37%, 40%) among non-exercisers (difference 11%; 95% CI: 8%, 13%; p < 0.001). Compared to patients with low (<6 MET-h/wk) levels of exercise (42%), 11% fewer patients with moderate (6-20.24 MET-h/wk) to high (>20.25 MET-h/wk) levels of exercise reported CIPN. Exercise was associated with reduced prevalence of all CIPN symptoms regardless of chemotherapy type. CONCLUSION: CIPN may persist several years following chemotherapy among patients with breast cancer but is significantly reduced by exercise in a dose-dependent manner.

o8G Site-Specifically Modified tRF-1-AspGTC: A Novel Therapeutic Target and Biomarker for Pulmonary Hypertension.

RATIONALE: Hypoxia and oxidative stress contribute to the development of pulmonary hypertension (PH). tRNA-derived fragments play important roles in RNA interference and cell proliferation, but their epitranscriptional roles in PH development have not been investigated. OBJECTIVE: We aimed to gain insight into the mechanistic contribution of oxidative stress-induced 8-oxoguanine in pulmonary vascular remodeling. METHODS AND RESULTS: Through small RNA modification array analysis and quantitative polymerase chain reaction, a significant upregulation of the 8-oxoguanine-modified tRF-1-AspGTC was found in the lung tissues and the serum of patients with PH. This modification occurs at the fifth 8-oxoguanine (5o8G) tRF in the seed region of the tRNA-derived fragments. Inhibition of the 5o8G tRF reversed hypoxia-induced proliferation and apoptosis resistance in pulmonary artery smooth muscle cells. Further investigation unveiled that the 5o8G tRF retargeted mRNA of WNT5A and CASP3 and inhibited their expression. Ultimately, BMPR2 (bone morphogenetic protein receptor 2)-reactive oxygen species/5o8G tRF/WNT5A signaling pathway exacerbated the progression of PH. CONCLUSIONS: Our study highlights the role of site-specific 8-oxoguanine-modified tRF in promoting the development of PH. Our findings present a promising therapeutic avenue for managing PH and propose 5o8G tRF as a potential innovative marker for diagnosing this disease.

Codonopsis radix: a review of resource utilisation, postharvest processing, quality assessment, and its polysaccharide composition.

Codonopsis radix is the dried root of C. pilosula (Franch.) Nannf., C. pilosula Nannf. var. modesta (Nannf.) L. T. Shen, or C. tangshen Oliv., constitutes a botanical medicine with a profound historical lineage. It encompasses an array of bioactive constituents, including polyacetylenes, phenylpropanoids, alkaloids, triterpenoids, and polysaccharides, conferring upon it substantial medicinal and edible values. Consequently, it has garnered widespread attention from numerous scholars. In recent years, driven by advancements in modern traditional Chinese medicine, considerable strides have been taken in exploring resources utilization, traditional processing, quality evaluation and polysaccharide research of Codonopsis radix. However, there is a lack of systematic and comprehensive reporting on these research results. This paper provides a summary of recent advances in Codonopsis research, identifies existing issues in Codonopsis studies, and offers insights into future research directions. The aim is to provide insights and literature support for forthcoming investigations into Codonopsis.