Optical imaging is highly valued for its superior temporal and spatial resolution. This is particularly important in near-infrared II (NIR-II, 1 000-3 000 nm) imaging, which offers advantages such as reduced tissue absorption, minimal scattering, and low autofluorescence. These characteristics make NIR-II imaging especially suitable for deep tissue visualization, where high contrast and minimal background interference are critical for accurate diagnosis and monitoring. Currently, inorganic fluorescent probes—such as carbon nanotubes, rare earth nanoparticles, and quantum dots—offer high brightness and stability. However, they are hindered by ambiguous structures, larger sizes, and potential accumulation toxicity in vivo. In contrast, organic fluorescent probes, including small molecules and polymers, demonstrate higher biocompatibility but are limited by shorter emission wavelengths, lower quantum yields, and reduced stability. Recently, gold clusters have emerged as a promising class of nanomaterials with potential applications in biocatalysis, fluorescence sensing, biological imaging, and more. Water-soluble gold clusters are particularly attractive as fluorescent probes due to their remarkable optical properties, including strong photoluminescence, large Stokes shifts, and excellent photostability. Furthermore, their outstanding biocompatibility—attributed to good aqueous stability, ultra-small hydrodynamic size, and high renal clearance efficiency—makes them especially suitable for biomedical applications. Gold clusters hold significant potential for NIR-II fluorescence imaging. Atomic-precision gold clusters, typically composed of tens to hundreds of gold atoms and measuring only a few nanometers in diameter, possess well-defined three-dimensional structures and clear spatial coordination. This atomic-level precision enables fine-tuned structural regulation, further enhancing their fluorescence properties. Variations in cluster size, surface ligands, and alloying elements can result in distinct physicochemical characteristics. The incorporation of different atoms can modulate the atomic and electronic structures of gold clusters, while diverse ligands can influence surface polarity and steric hindrance. As such, strategies like alloying and ligand engineering are effective in enhancing both fluorescence and catalytic performance, thereby meeting a broader range of clinical needs. In recent years, gold clusters have attracted growing attention in the biomedical field. Their application in NIR-II imaging has led to significant progress in vascular, organ, and tumor imaging. The resulting high-resolution, high signal-to-noise imaging provides powerful tools for clinical diagnostics. Moreover, biologically active gold clusters can aid in drug delivery and disease diagnosis and treatment, offering new opportunities for clinical therapeutics. Despite the notable achievements in fundamental research and clinical translation, further studies are required to address challenges related to the standardized synthesis and complex metabolic behavior of gold clusters. Resolving these issues will help accelerate their clinical adoption and broaden their biomedical applications.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.

ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

This study explores the basic characteristics and potential functions of the terpene synthase(TPS) gene family members in Lonicera japonica. The L. japonica TPS(LjTPS) gene family was identified and functionally analyzed using bioinformatics methods. The results showed that a total of 70 members of the LjTPS gene family were identified in L. japonica, with protein lengths ranging from 130 to 1 437 amino acids. Most of these proteins were hydrophilic, and they were unevenly distributed across nine chromosomes. Phylogenetic analysis showed that the LjTPS gene family members were divided into six subfamilies, mainly consisting of members from the TPS-a, TPS-b, and TPS-e subfamilies. Promoter cis-acting element analysis showed that LjTPS members contained a large number of stress-responsive cis-acting elements. Aphid inoculation experiments showed that key enzyme genes in the MVA pathway for terpenoid backbone synthesis in L. japonica, such as HMGS, HMGR, MK, MPD, and the key enzyme gene in the DXP pathway, DXS, exhibited an initial increase followed by a decrease under aphid stress. The qRT-PCR analysis showed that the expression levels of the α-farnesene synthase genes LjTPS34 and LjTPS39 were down-regulated, while the expression levels of(E)-β-caryophyllene synthase genes LjTPS15 and LjTPS17 were up-regulated 12 h before aphid feeding, then began to decline. Farnesyl pyrophosphate synthase(FPS), which interacted with these genes, also displayed a pattern of increasing followed by decreasing expression. The expression of linalool synthase genes LjTPS12 and LjTPS33 was significantly up-regulated after 72 h of aphid feeding(P<0.000 1), reaching 24.39 and 22.64 times the initial expression, respectively. This pattern was in close alignment with the trend of linalool content in L. japonica. This study provides a theoretical foundation for future research on the interaction between L. japonica and pests, as well as on the functional roles of the LjTPS gene family.
Animals ; Aphids/physiology* ; Alkyl and Aryl Transferases/chemistry* ; Lonicera/parasitology* ; Phylogeny ; Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Multigene Family ; Terpenes/metabolism*

Bufalin(BF)has a significant anti-tumor effect, but its clinical application is severely restricted by its high toxicity and poor water solubility. In this study, Scrophularia ningpoensis polysaccharide(SNP)and ursodeoxycholic acid(UDCA) were synthesized into an SNP-UDCA conjugate. BF was encapsulated to prepare BF/SNP-UDCA nanoparticles(NPs). The amphiphilic compound SNP-UDCA was synthesized via the one-step method, and its structure was characterized by Fourier-transform infrared spectroscopy(FT-IR)and proton nuclear magnetic resonance(~1H-NMR). The preparation process of BF/SNP-UDCA NPs was optimized through single-factor investigations. The encapsulation efficiency and drug-loading capacity of BF/SNP-UDCA NPs were determined by high-performance liquid chromatography(HPLC). The molecular form of BF/SNP-UDCA NPs was characterized by using a transmission electron microscope, X-ray diffraction(XRD), and differential scanning calorimeter(DSC). Additionally, the stability of BF/SNP-UDCA NPs was evaluated. The release behavior of BF/SNP-UDCA NPs at different pH values was determined by dialysis. The in vitro anti-tumor effect of BF/SNP-UDCA NPs was evaluated by MTT cytotoxicity assay, flow cytometry for apoptosis, and cellular uptake. The in vitro liver targeting was evaluated by measuring cellular uptake by laser confocal microscopy. The results demonstrated that the SNP-UDCA conjugate was successfully synthesized through an esterification reaction between SNP and UDCA. The preparation process of BF/SNP-UDCA NPs was as follows: the feed ratio of SNP-UDCA to BF was 2∶1, the ultrasonic time was 30 minutes, and the stirring time was two hours. The prepared BF/SNP-UDCA NPs were spherical in shape, with a particle size of(252.74±6.05)nm, an encapsulation efficiency of 65.00%±2.51%, and a drug-loading capacity of 6.80%±0.44%. The XRD and DSC results indicated that BF was encapsulated within the NPs and existed in a molecular or amorphous state. The short-term stability of BF/SNP-UDCA NPs and stability in DMEM medium are good, and their in vitro release behavior followed the first-order equation and was pH-dependent according to the in vitro experiment. Compared with BF, BF/SNP-UDCA NPs at the same concentration showed significantly stronger cytotoxicity and apoptotic effects on HepG2 cells(P<0.05, P<0.01). The uptake of coumarin 6(C6)/SNP-UDCA NPs in HepG2 cells was time-dependent and higher than that in HeLa cells at the same concentration of C6/SNP-UDCA NPs. Moreover, after treatment with SNP, the uptake of C6/SNP-UDCA NPs in HepG2 cells decreased. In conclusion, the preparation process of BF/SNP-UDCA NPs was simple and feasible. BF/SNP-UDCA NPs could enhance the targeting ability and inhibitory effect of BF on liver cancer cells. This study will provide a foundation for liver-targeting nanoformulations of BF.
Bufanolides/pharmacology* ; Nanoparticles/chemistry* ; Humans ; Drug Carriers/chemistry* ; Ursodeoxycholic Acid/chemistry* ; Antineoplastic Agents/pharmacology* ; Polysaccharides/chemistry* ; Scrophularia/chemistry* ; Liver Neoplasms/physiopathology* ; Hep G2 Cells

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in adolescents, with potential causes etiologies associated with mesenchymal stem cells, genetic factors, histological features, and biomechanical aspects. Biomechanically, the pelvis, serving as the central and majort load-bearing structure, exhibits morphological and alignment abnormalities highly correlated with the development of AIS. Recent studies have extensively explored three-dimensional pelvic parameters and kinematics, demonstrating that abnormal pelvic characteristics may contribute to AIS onset and progression and are increasingly incorporated into clinical interventions. This review summarizes sagittal and coronal features of the spine-pelvis, as well as the influence of three-dimensional kinematic features on the pathogenesis of AIS, providing insights for advancing the study of spine-pelvis features related to AIS.
Humans ; Scoliosis/pathology* ; Adolescent ; Spine/pathology* ; Pelvis/pathology* ; Biomechanical Phenomena

PURPOSE: To evaluate the relationship between the timing of thoracic endovascular aortic repair (TEVAR) for blunt thoracic aortic injury (BTAI) and prognosis. METHODS: This is a single-center retrospective cohort study. Patients who received TEVAR for BTAI at our institution from October 2016 to September 2023 were divided into 2 categories depending on the injury severity score (ISS) (≤ 25 vs. > 25) and when the TEVAR was performed for BTAI (within 24 h vs. after 24 h), respectively. The analysis included all patients who received TEVAR treatment after being diagnosed with BTAI through whole-body CT angiography. Patients treated with open repair and non-operative management were excluded. After propensity-score matching for various factors, outcomes during hospitalization and follow-up were compared. These factors included demographics, comorbidities, concomitant injuries, cause and location of aortic injury, Glasgow coma scale score, society for vascular surgery grading, hemoglobin concentration, creatinine concentration, shock, systolic blood pressure, and heart rate at admission. The comparison was conducted using SPSS 26 software. Continuous variables were presented as either the mean ± standard deviation or median (Q₁, Q₃), and were compared using either the t-test or the Mann-Whitney U test. Categorical variables were expressed as n (%), and comparisons were made between the 2 groups using the χ² test or Fisher's exact test. Statistical significance was defined as a 2-sided p < 0.05. RESULTS: In total, 110 patients were involved in the study, with 65 (59.1%) patients having ISS scores > 25 and 32 (29.1%) receiving immediate TEVAR. The perioperative overall mortality rate in the group with ISS > 25 was significantly higher than that in the group with ISS ≤ 25 (11 (16.9%) vs. 2 (4.4%), p < 0.001). Upon admission, the elective group exhibited a notably higher Glasgow coma scale score (median (Q₁, Q₃)) compared to the immediate group (15 (12, 15) vs. 13.5 (9, 15), p = 0.039), while the creatinine concentration (median (Q₁, Q₃)) at admission was significantly higher in the immediate group (90.5 (63.8, 144.0) vs. 71.5 (58.3, 80.8), p = 0.012). The final sample included 52 matched patients. Complications occurred significantly less frequently in the elective group compared to the immediate group (16 (50.0%) vs. 3 (10.0%), p < 0.001). Single-factor analysis of variance showed that complications in hospitalized patients were significantly associated with immediate TEVAR as the sole independent risk factor (odds ratio: 9.000, 95% confidence interval: 2.266-35.752, p = 0.002). CONCLUSION In this propensity-score matched analysis of patients undergoing TEVAR for BTAI, elective TEVAR was significantly associated with a lower risk of complication rates. In this study using propensity-score matching, patients who underwent elective TEVAR for BTAI had lower complication rates than immediate TEVAR.
Humans ; Retrospective Studies ; Male ; Aorta, Thoracic/surgery* ; Female ; Endovascular Procedures/methods* ; Wounds, Nonpenetrating/mortality* ; Middle Aged ; Adult ; Aged ; Injury Severity Score ; Elective Surgical Procedures ; Time Factors ; Treatment Outcome ; Endovascular Aneurysm Repair

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*