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*

OBJECTIVE: To compare the therapeutic efficacy and safety of local anesthesia and spinal anesthesia for the patients with varicocele (VC) who underwent microsurgical varicocelectomy (MV). METHODS: We retrospectively analyzed the data of VC patients who underwent MV treatment at the Andrology Department of the Affiliated Ruikang Hospital of Guangxi University of Chinese Medicine from May 2020 to March 2023. Cases with complete clinical data and follow-up evaluation were selected and divided into a control group (spinal anesthesia) and an observation group (local anesthesia) according to different anesthesia methods. The surgical time (including anesthesia time), visual analogue scale (VAS) score for pain, hospital stay, treatment cost, sperm concentration, forward motile sperm rate, and normal sperm morphology rate after three months of surgery, as well as postoperative complications and recurrence rate were compared between the two groups. RESULTS: A total of 107 eligible cases were included, with 56 cases in the control group and 51 cases in the observation group. There was no significant difference in the VAS score for pain during and after four hours of surgery, as well as postoperative complications, and recurrence rate between the two groups (P> 0.05). There was an significant increase in sperm concentration, forward motile sperm rate, and normal sperm morphology rate in both of two groups after three months of surgery (P<0.05). However, there was no significant difference between the two groups three months after surgery (P>0.05). The surgical time and hospital stay were shorter than those of the control group (P<0.05). And the treatment cost in observation group was lower than that of the control group (P<0.05). CONCLUSION Both local anesthesia and lumbar anesthesia for MV treatment of VC have good efficacy and safety. However, patients treated with MV under local anesthesia for VC have obvious advantages in terms of operation time (including anesthesia time), hospital stay, and treatment cost, which is worthy of clinical promotion and application.
Humans ; Male ; Varicocele/surgery* ; Retrospective Studies ; Microsurgery ; Anesthesia, Spinal ; Adult ; Treatment Outcome ; Anesthesia, Local

Anthoceros angustus Steph. is rich in phenolic acids such as rosmarinic acid (RA). Phenylalanine ammonia-lyase (PAL) is an entry enzyme in the phenylpropanoid pathway of plants, playing an important role in the biosynthesis of RA. To investigate the important role of PAL in rosmarinic acid synthesis, two PAL genes (designated as AanPAL1 and AanPAL2) were cloned from A. angustus, encoding 755 and 753 amino acid residues, respectively. The AanPAL deduced amino acid sequences contain the conserved domains of PAL and the core active amino acid residues Ala-Ser-Gly. The phylogenetic analysis indicated that AanPAL1 and AanPAL2 were clustered with PALs from bryophytes and ferns and had the shortest evolutionary distance with the PALs from Physcomitrella patens. Quantitative real-time PCR results showed that the expression of AanPAL1 and AanPAL2 was induced by exogenous methyl jasmonate (MeJA). HPLC results showed that the MeJA treatment significantly increased the accumulation of RA. AanPAL1 and AanPAL2 were expressed in Escherichia coli and purified by histidine-tag affinity chromatography. The recombinant proteins catalyzed the conversion of L-phenylalanine to generate trans-cinnamic acid with high efficiency, with the best performance at 50 ℃ and pH 8.0. The K_m and k_cat of AanPAL1 were 0.062 mmol/L and 4.35 s^-1, and those of AanPAL2 were 0.198 mmol/L and 14.48 s^-1, respectively. The specific activities of AanPAL1 and AanPAL2 were 2.61 U/mg and 8.76 U/mg, respectively. The two enzymes had relatively poor thermostability but good pH stability. The high activity of AanPAL2 was further confirmed via whole-cell catalysis with recombinant E. coli, which could convert 1 g/L L-phenylalanine into trans-cinnamic acid with a yield of 100% within 10 h. These results give insights into the regulatory role of AanPAL in the biosynthesis of RA in A. angustus and provide candidate enzymes for the biosynthesis of cinnamic acid.
Phenylalanine Ammonia-Lyase/metabolism* ; Cloning, Molecular ; Cinnamates/metabolism* ; Recombinant Proteins/metabolism* ; Rosmarinic Acid ; Depsides/metabolism* ; Escherichia coli/metabolism* ; Amino Acid Sequence ; Plant Proteins/metabolism* ; Phylogeny ; Acetates/pharmacology* ; Cyclopentanes ; Oxylipins

Objective To observe the clinical efficacy of electroacupuncture at Shuigou(DU26)combined with warming-needle moxibustion in the treatment of acute cerebral infarction.Methods Nighty-six patients with acute cerebral infarction were randomly divided into observation group and control group,48 cases in each group.Both groups were given routine basic treatment.The control group was treated with warming-needle moxibustion.The observation group was treated with electroacupuncture at Shuigou point on the basis of the control group.The treatment was performed 5 days a week for a total of 3 weeks.After 3 weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes of National Institutes of Health Stroke Scale(NIHSS)score,Barthel Index(BI)score and Fugl-Meyer motor function assessment scale score of the two groups were observed before and after treatment.The changes of interleukin-6(IL-6),high-sensitivity C-reactive protein(hs-CRP)and homocysteine(Hey)levels were compared before and after treatment between the two groups.The safety and adverse reactions of the two groups were evaluated.Results(1)The total effective rate of the observation group was 95.83％(46/48),and that of the control group was 81.25％(39/48).The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the NIHSS scores,BI scores,and FMA scores of the patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the NIHSS scores,BI scores,and FMA scores,with a statistically significant difference(P＜0.05).(3)After treatment,the serum IL-6,hs-CRP,and Hey levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum inflammatory factors of IL-6,hs-CRP,and Hey levels,with statistically significant differences(P＜0.05).(4)Comparing the incidence of adverse reactions between the observation group and the control group,the difference was not statistically significant(P＞0.05).Conclusion Electroacupuncture at Shuigou point combined with warming-needle moxibustion in the treatment of acute cerebral infarction can significantly promote the recovery of patients'neurological function,thus improving their motor and living ability,effectively reducing the levels of inflammatory factors and homocysteine,and the clinical efficacy is remarkable.

Objective To investigate the effect of Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the changes of gastric mucosal pathological score and gastrointestinal hormones in patients with chronic atrophic gastritis(CAG)of liver stagnation and spleen deficiency type.Methods A total of 156 cases of CAG patients with liver stagnation and spleen deficiency syndrome were randomly divided into a control group and an observation group,78 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The changes in the scores of traditional Chinese medicine(TCM)symptoms such as epigastric distention and pain,poor appetite,loose stools,limb weakness,belching and acid regurgitation,gastric mucosal pathological scores and serum levels of gastrointestinal hormones of motilin(MTL)and gastrin(GAS)in the two groups were observed before and after treatment.The negative conversion rate of Helicobacter pylori(Hp)in the two groups was compared,and the clinical efficacy and safety of the two groups were evaluated.Results(1)After four weeks of treatment,the total effective rate of the observation group was 93.59％(73/78),which was significantly higher than 82.05％(64/78)of the control group,and the difference between the two groups was statistically significant(P＜0.05).(2)After treatment,the scores of TCM symptoms such as epigastric distention and pain,poor appetite,loose stool,limb weakness,belching and acid regurgitation in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the pathological scores of gastric mucosa in the two groups were significantly decreased when compared with those before treatment(P＜0.05),and the decrease in the observation group was more significant than that in the control group(P＜0.01).(4)After four weeks of treatment,the negative conversion rate of Hp in the observation group was 91.03％(71/78),which was significantly higher than that in the control group(75.64％,59/78),and the difference between the two groups was statistically significant(P＜0.05).(5)After treatment,the level of serum GAS in the two groups was significantly decreased(P＜0.05)and the serum MTL level was significantly increased compared with that before treatment(P＜0.05);the decrease of serum GAS level and the increase of serum MTL level in the observation group were significantly superior to those in the control group(P＜0.05).(6)There were no obvious abnormalities in the routine test of blood,urine,stool,kidney function,and liver function,electrocardiograph and other safety indicators during the treatment of the two groups of patients,no adverse reactions such as dizziness,rash and chest distress occurred either,with high safety.Conclusion Xiao Chaihu Decoction combined with Xiangsha Liujunzi Decoction exerts a significant therapeutic effect on GAS of liver stagnation and spleen deficiency type,which can effectively relieve the clinical symptoms,improve the pathological changes of gastric mucosa and promote Hp negative conversion.The therapeutic mechanism may be related to the regulation of gastrointestinal hormone levels.

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.

AIM:To investigate the impact of aquaporin 4(AQP4)expression inhibition on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion(I/R)injury,and to elucidate its underlying mechanism.METHODS:Cerebral I/R injury was induced in mice via transient middle cerebral artery occlusion(tMCAO).Totally 60 mice were randomly divided into sham group,I/R group,AQP4 inhibition group,and 3-methyladenine(3-MA)group,with 15 mice in each group.Among them,the mice in sham and I/R groups received intraperitoneal injections of normal saline,while those in AQP4 inhibition group and 3-MA group received intraperitoneal injections of AER-271(2 mg·kg-1·d-1)and AER-271+3-MA(2 mg·kg-1·d-1)for 3 d,respectively,once per day.Longa score was adopted to assess the neu-rological function,and to record changes in body weight.Cerebral infarction volume and histopathological alterations were evaluated using hematoxylin-eosin staining.Western blot analysis was performed to determine the levels of AQP4,LC3-Ⅱ,P62 and cleaved caspase-3,while the LC3-Ⅱ,P62,cleaved caspase-3 and NeuN(neuronal marker)colocalization and expression assessment were conducted with immunofluorescence.RESULTS:The mice in I/R and AQP4 inhibition groups exhibited extensive cerebral infarction,cerebral edema,and elevated Longa scores.However,in comparision to I/R group,the mice in AQP4 inhibition group showed significantly reduced cerebral infarct volume,cerebral edema vol-ume,and Longa score(P<0.05).Additionally,in contrast to sham group,the mice in I/R group displayed increased ex-pression of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.01),accompanied by decreased body weight and P62 expression(P<0.05 or P<0.01).Furthermore,compared with I/R group,the mice in both AQP4 inhibition group and 3-MA group demonstrated a decrease in the expression levels of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.05 or P<0.01),along with increased body weight and P62 expression(P<0.05 or P<0.01).Nonetheless,no significant differences were ob-served between AQP4 inhibition group and 3-MA group regarding Longa score,cerebral infarct volume,body weight,and the expression of AQP4,LC3-Ⅱ,cleaved caspase-3 and P62.CONCLUSION:Inhibition of AQP4 expression signifi-cantly reduces cerebral infarction area and nerve injury severity in tMCAO mice.Moreover,AQP4 expression inhibition decelerates autophagy and apoptosis after cerebral infarction,with the additional autophagy inhibitor showing no notable impact on the protective effect of AQP4 inhibition.

BACKGROUND:Knee osteoarthritis is a degenerative disease caused by multiple factors.Its pathogenesis is complex and still unclear.Chinese medicine in the treatment of knee osteoarthritis is fruitful,and in-depth study of Chinese medicine in the treatment of knee osteoarthritis is of great significance. OBJECTIVE:To review the progress of Chinese medicine monomers and compounds in the treatment of knee osteoarthritis and to provide ideas and reference for the effective prevention and treatment of knee osteoarthritis. METHODS:CNKI,WanFang,VIP,PubMed,MEDLINE,Nature,and Cochrane databases were retrieved for relevant literature published from database inception to 2022.The keywords were"knee osteoarthritis,cartilage damage,traditional Chinese medicine,Chinese herbal compound,treatment"in Chinese and English.Duplicates and obsolete non-referenced literature were excluded,and a total of 62 standard papers were included for further review. RESULTS AND CONCLUSION:Some of the pathogeneses of knee osteoarthritis include immune inflammatory response,chondrocyte autophagy and apoptosis,vascular endothelial growth factor level and biomechanical imbalance.The mechanisms by which traditional Chinese medicine treats knee osteoarthritis mainly focus on regulating inflammatory factor levels,chondrocyte autophagy and apoptosis,and vascular endothelial growth factor level and improving cartilage performance,so as to delay the occurrence and development of knee osteoarthritis.