ObjectiveTransfer RNA-derived fragments (tRFs) are a recently characterized and rapidly expanding class of small non-coding RNAs, typically ranging from 13 to 50 nucleotides in length. They are derived from mature or precursor tRNA molecules through specific cleavage events and have been implicated in a wide range of cellular processes. Increasing evidence indicates that tRFs play important regulatory roles in gene expression, primarily by interacting with target messenger RNAs (mRNAs) to induce transcript degradation, in a manner partially analogous to microRNAs (miRNAs). However, despite their emerging biological relevance and potential roles in disease mechanisms, there remains a significant lack of computational tools capable of systematically predicting the interaction landscape between tRFs and their target mRNAs. Existing databases often rely on limited interaction features and lack the flexibility to accommodate novel or user-defined tRF sequences. The primary goal of this study was to develop a machine learning based prediction algorithm that enables high-throughput, accurate identification of tRF:mRNA binding events, thereby facilitating the functional analysis of tRF regulatory networks. MethodsWe began by assembling a manually curated dataset of 38 687 experimentally verified tRF:mRNA interaction pairs and extracting seven biologically informed features for each pair: (1) AU content of the binding site, (2) site pairing status, (3) binding region location, (4) number of binding sites per mRNA, (5) length of the longest consecutive complementary stretch, (6) total binding region length, and (7) seed sequence complementarity. Using this dataset and feature set, we trained 4 distinct machine learning classifiers—logistic regression, random forest, decision tree, and a multilayer perceptron (MLP)—to compare their ability to discriminate true interactions from non-interactions. Each model’s performance was evaluated using overall accuracy, receiver operating characteristic (ROC) curves, and the corresponding area under the ROC curve (AUC). The MLP consistently achieved the highest AUC among the four, and was therefore selected as the backbone of our prediction framework, which we named tRF Prospect. For biological validation, we retrieved 3 high-throughput RNA-seq datasets from the gene expression omnibus (GEO) in which individual tRFs were overexpressed: AS-tDR-007333 (GSE184690), tRF-3004b (GSE197091), and tRF-20-S998LO9D (GSE208381). Differential expression analysis of each dataset identified genes downregulated upon tRF overexpression, which we designated as putative targets. We then compared the predictions generated by tRF Prospect against those from three established tools—tRFTar, tRForest, and tRFTarget—by quantifying the number of predicted targets for each tRF and assessing concordance with the experimentally derived gene sets. ResultsThe proposed algorithm achieved high predictive accuracy, with an AUC of 0.934. Functional validation was conducted using transcriptome-wide RNA-seq datasets from cells overexpressing specific tRFs, confirming the model’s ability to accurately predict biologically relevant downregulation of mRNA targets. When benchmarked against established tools such as tRFTar, tRForest, and tRFTarget, tRF Prospect consistently demonstrated superior performance, both in terms of predictive precision and sensitivity, as well as in identifying a higher number of true-positive interactions. Moreover, unlike static databases that are limited to precomputed results, tRF Prospect supports real-time prediction for any user-defined tRF sequence, enhancing its applicability in exploratory and hypothesis-driven research. ConclusionThis study introduces tRF Prospect as a powerful and flexible computational tool for investigating tRF:mRNA interactions. By leveraging the predictive strength of deep learning and incorporating a broad spectrum of interaction-relevant features, it addresses key limitations of existing platforms. Specifically, tRF Prospect: (1) expands the range of detectable tRF and target types; (2) improves prediction accuracy through multilayer perceptron model; and (3) allows for dynamic, user-driven analysis beyond database constraints. Although the current version emphasizes miRNA-like repression mechanisms and faces challenges in accurately capturing 5'UTR-associated binding events, it nonetheless provides a critical foundation for future studies aiming to unravel the complex roles of tRFs in gene regulation, cellular function, and disease pathogenesis.

Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

Dopamine, as a catecholamine neurotransmitter widely distributed in the central nervous system, is involved in physiological functions such as motivation, arousal, reinforcement, and movement through various dopamine signaling pathways. The hippocampus receives dopaminergic neuron projections from regions such as the ventral tegmental area, locus coeruleus, and substantia nigra. Through D1-like and D2-like receptors, dopamine exerts significant regulatory effects such as spatial navigation, episodic memory, fear, anxiety, and reward. This review mainly summarizes the research progress on the functions of dopamine in the hippocampus from aspects including the sources of dopamine, receptor distribution and function, and the association of hippocampal dopamine system dysregulation with neurodegenerative diseases. The aim is to provide insights into the involvement of the dopamine system in hippocampal functions and the diagnosis and treatment of related diseases.
Hippocampus/physiology* ; Dopamine/physiology* ; Humans ; Animals ; Receptors, Dopamine D2/physiology* ; Memory/physiology* ; Signal Transduction/physiology* ; Neurodegenerative Diseases/physiopathology*

BACKGROUND:The nuclear factor-κB signaling pathway plays an important role in the pathogenesis of osteoporosis.In recent years,increasing studies have shown that terpenoid herbal monomer compounds can inhibit the activity of bone resorbing cells and promote the differentiation of bone forming cells via the nuclear factor-κB signaling pathway,thus reducing bone resorption and increasing bone formation,which has certain preventive and therapeutic effects on osteoporosis. OBJECTIVE:By analyzing and summarizing the domestic and international literature,to investigate the relationship between nuclear factor-κB signaling pathway and osteoporosis in depth,elucidate the mechanism of terpenoid monomer compounds in regulating the nuclear factor-κB signaling pathway to prevent osteoporosis,and systematically summarize the terpenoid monomer compounds targeting to regulate the nuclear factor-κB signaling pathway to prevent osteoporosis. METHODS:According to the proposed inclusion and exclusion criteria,two researchers searched for relevant articles published from database inception to December 2022 in CNKI and PubMed using the search terms"NF-κB,osteoporosis,osteoblasts,osteoclasts,angiogenesis,traditional Chinese medicine,terpenoid"in Chinese and English,respectively.A third researcher summarized and organized the literature and 75 articles were finally included for a systematic review. RESULTS AND CONCLUSION:The nuclear factor-κB signaling pathway mediates the onset and progression of osteoporosis by regulating the differentiation and proliferation of osteoblasts and osteoclasts,as well as angiogenesis.Activation of the nuclear factor-κB signaling pathway negatively regulates the proliferation and differentiation of osteoblasts.Activation of the nuclear factor-κB signaling pathway enhances osteoclast activity and inhibits osteoblast growth,thereby inhibiting compensatory bone production to maintain bone homeostasis.However,over-activation of the nuclear factor-κB signaling pathway can lead to osteoporosis.The nuclear factor-κB signaling pathway is involved in the"angiogenesis-osteogenesis"coupling by upregulating the expression levels of cytokines such as angiopoietin-1,platelet-derived growth factor BB and vascular endothelial growth factor,which promote the growth of blood vessels in bone.The terpenoid herbal monomer compounds are used in the field of tissue engineering to promote the proliferation and differentiation of bone cells,thereby promoting the growth and repair of bone tissue.Terpenoid herbal monomer compounds can prevent and treat osteoporosis by inhibiting the degradation of nuclear factor-κB inhibitor,blocking nuclear factor-κB/p65 phosphorylation and nuclear translocation,thereby weakening the nuclear factor-κB signaling pathway,promoting osteoblast differentiation and inhibiting osteoclast formation.Currently,research on the regulation of nuclear factor-κB signaling pathway by monomeric compounds of terpenoids to prevent osteoporosis is mainly based on in vitro cellular experiments and animal models,and there is a lack of research on the complex physiological and pathological processes in humans.In the future,more clinical trials and studies are needed to further clarify the mechanism of action and efficacy of the nuclear factor-κB signaling pathway involved in the intervention of osteoporosis.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

With the improvement of China's socioeconomic status,the issue of aging has become increasingly prominent,making cerebral infarction a common disease among the elderly.In recent years,research on cerebral infarction has gradually deepened,shifting focus from merely protecting and repairing neurons to emphasizing the complex interplay between inflammatory response and autophagy in the brain vascular unit,covering various aspects such as the blood-brain barrier,astrocytes,microglia,and autophagy.This shift in research direction has provided us with a profound understanding of the mechanisms underlying cerebral infarction,offering strong support for innovative future treatment strategies.In this review,we delved into the importance of the interplay between inflammatory response and autophagy in the pathogenesis of cerebral infarction,emphasized the intricate interactions among these biological components,which might lay the groundwork for more effective managements and treatments of cerebral infarction.By comprehensively reviewing existing literatures,we proposed future research directions,aiming to provide more scientific and systematic guidance for the clinical management and treatment of cerebral infarction.

Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P＜0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P＞0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95％CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.

Objective:To determine the risk factors of reoperation and mortality after complete atrioventricular septal defect repair, and to evaluate the medium and long-term prognosis.Methods:From March 2008 to March 2022, a total of 266 children were selected from the Department of Thoracic and Cardiovascular Surgery, Nanjing Children's Hospital, who underwent the complete atrioventricular septal defect repair. Exclusion of children with conotrucal anomaly such as tetralogy of Fallot, transposition of the great arteries, and right ventricular double outlet. Demographic characteristics, surgical data, postoperative follow-up and associated risk factors were analyzed.Results:All the children were repaired with modified single-piece method for the first time, and 26 children were reoperated because of severe left atrioventricular valve regurgitation, left ventricular outflow tract obstruction and atrioventricular block. The 1-year, 3-year and 5-year overall survival rate and freedom from reoperation rate of all children were (98.1±0.8)%, (97.3±1.0)%, (96.2±1.2)%, (96.6±1.1)%, (93.9±1.5)% and (92.2±1.7)%, respectively. A total of 11 (42.3%) early reoperations and 15 (57.7%) late reoperations were performed, of which 1-year, 3-year and 5-year survival rates were (92.3±5.2)%, (82.1±8.3)% and (76.6±9.4)% respectively. Multifactorial analysis showed that age <3 months and left atrioventricular regurgitation >grade 2 at 24 hours postoperatively were independent risk factors for reoperation, whereas age <3 months and experience of reoperation were independent risk factors for death of children.Conclusion:Complete atrial septal defects have excellent surgical outcomes, but some children still require reoperation, and age <3 months and postoperative left atrioventricular valve regurgitation(LAVVR)>2 grades remain important predictors of their surgical prognosis.

OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) combined with modified neurolysis in treatment of diabetic foot ulcer (DFU) through a prospective randomized controlled study. METHODS: The patients with DFU and diabetic peripheral neuropathy, who were admitted between February 2020 and February 2022, were selected as the research objects, of which 31 cases met the selection criteria and were included in the study. The patients were divided into two groups by random number table method. The 15 patients in the trial group were treated with TTT combined with modified neurolysis, and the 16 patients in the control group received treatment with TTT alone. There was no significant difference in gender, age, duration of DFU, ulcer area, Wagner classification, as well as preoperative foot skin temperature, visual analogue scale (VAS) score, ankle-brachial index (ABI), motor nerve conduction velocity (MNCV) of the common peroneal nerve, MNCV of the tibial nerve, MNCV of the deep peroneal nerve, two-point discrimination (2-PD) of heel, and cross-sectional area (CSA) of the common peroneal nerve between the two groups ( P>0.05). The time for ulcer healing, foot skin temperature, VAS scores, ABI, 2-PD of heel, and CSA of the common peroneal nerve before operation and at 6 and 12 months after operation were recorded and compared between groups. The differences in MNCV of the common peroneal nerve, MNCV of the tibial nerve, and MNCV of the deep peroneal nerve between pre-operation and 12 months after operation were calculated. RESULTS: All patients in both groups were followed up 12-24 months (mean, 13.9 months). The surgical incisions in both groups healed by first intention and no needle tract infections occurred during the bone transport phase. Ulcer wounds in both groups healed successfully, and there was no significant difference in the healing time ( P>0.05). During the follow-up, there was no ulcer recurrences. At 12 months after operation, the MNCV of the common peroneal nerve, the MNCV of the tibial nerve, and the MNCV of the deep peroneal nerve in both groups accelerated when compared to preoperative values ( P<0.05). Furthermore, the trial group exhibited a greater acceleration in MNCV compared to the control group, and the difference was significant ( P<0.05). The foot skin temperature, VAS score, ABI, 2-PD of heel, and CSA of the common peroneal nerve at 6 and 12 months after operation significantly improved when compared with those before operation in both groups ( P<0.05). The 2-PD gradually improved over time, showing significant difference ( P<0.05). The 2-PD of heel and VAS score of the trial group were superior to the control group, and the differences were significant ( P<0.05). There was no significant difference in ABI, foot skin temperature, and CSA of the common peroneal nerve between groups after operation ( P>0.05). CONCLUSION Compared with TTT alone, the TTT combined with modified neurolysis for DFU can simultaneously solve both microcirculatory disorders and nerve compression, improve the quality of nerve function recovery, and enhance the patient's quality of life.
Humans ; Diabetic Foot/surgery* ; Microcirculation ; Prospective Studies ; Quality of Life ; Treatment Outcome ; Diabetes Mellitus

Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.
Humans ; Glucose ; Blood Glucose ; Insulin Resistance/physiology* ; Diabetes Mellitus, Type 2/diagnosis* ; Blood Glucose Self-Monitoring ; Time Factors ; Insulin