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*

OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans ; Biomechanical Phenomena ; Orthopedics ; Traumatology ; Software ; Medicine, Chinese Traditional ; Musculoskeletal System ; Models, Biological

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*

OBJECTIVE: To investigate the impacts of sulforaphane (SPN) on cell proliferation and apoptosis in acute promyelogenous leukemia by regulating the PI3K/Akt/mTOR signaling pathway. METHODS: NB4 cells were divided into 5 μmol/L SPN group, 10 μmol/L SPN group, 20 μmol/L SPN group, 740 Y-P (10 μmol/L) group and 20 μmol/L SPN+740 Y-P group, and the untreated NB4 cells were used as the control group. CCK-8, Hoechst 33342 staining, flow cytometry and monodansulfonylpentanediamine (MDC) were used to detect cell proliferation, apoptosis and autophagy, respectively. The expression levels of Bcl-2, Bax, cyclin D1 and LC3B mRNA were detected by qRT-PCR. Western blot was used to detect the expression levels of PI3K/Akt/mTOR pathway-related proteins in NB4 cells. RESULTS: Compared with the control group, the proliferation rate, Bcl-2, cyclin D1 mRNA expressions, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratio were greatly increased in the 740 Y-P group (P < 0.05), the apoptosis rate, percentage of MDC positive, Bax and LC3B mRNA expression levels were greatly decreased (P < 0.05). The proliferation rate, Bcl-2, cyclin D1 mRNA expression levels, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratio were greatly decreased in the 5 μmol/L SPN group, 10 μmol/L SPN group, and 20 μmol/L SPN group (P < 0.05), the apoptosis rate, percentage of MDC positive,Bax and LC3B mRNA expression levels were greatly increased, there were differences among different SPN treatment groups (P < 0.05). Compared with the 20 μmol/L SPN group, the proliferation rate, Bcl-2, cyclin D1 mRNA expression levels, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratio were greatly increased in the 20 μmol/L SPN+740 Y-P group(P < 0.05), the apoptosis rate, percentage of MDC positive, Bax and LC3B mRNA expression levels were greatly decreased (P < 0.05). Compared with the 740 Y-P group, the proliferation rate, Bcl-2, cyclin D1 mRNA expression levels, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratio in the 20 μmol/L SPN+740 Y-P group were greatly reduced (P < 0.05), the apoptosis rate, percentage of MDC positive, Bax and LC3B mRNA expression levels were greatly increased (P < 0.05). CONCLUSION SPN reduces the proliferation of acute promyelocytic leukemia cells and promotes cells apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway.
Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Humans ; TOR Serine-Threonine Kinases/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Isothiocyanates/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Sulfoxides ; Cell Line, Tumor ; Cyclin D1/metabolism*

Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo (TXL) capsule to treat atherosclerosis. However, clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable. In response, we developed this study to investigate the hypothesis that on the basis of statin therapy, treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome (ACS). The TXL-CAP study was an investigator-initiated, randomized, double-blind clinical trial conducted across 18 medical centers in China. Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness (FCT) < 100 μm and lipid arc > 90° as defined by optical coherence tomography (OCT) were recruited. A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL (n = 110) or placebo (n = 110) for a duration of 12 months. The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up. Secondary endpoints included: (1) changes of the maximum lipid arc and length of the target plaque, and the percentage of lipid, fibrous, and calcified plaques at the end of the 12-month period; (2) the incidence of composite cardiovascular events and coronary revascularization within the 12 months; (3) changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society (CCS) grading system and Seattle angina questionnaire (SAQ) score, respectively; and (4) changes in hs-CRP serum levels. The results of the TXL-CAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

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.

The study aimed to investigate the effect of the CD200R1 gene deletion on microglia activation and nigrostriatal dopamine neuron loss in the Parkinson's disease (PD) process. The CRISPR-Cas9 technology was applied to construct the CD200R1^-/- mice. The primary microglia cells of wild-type and CD200R1^-/- mice were cultured and treated with bacterial lipopolysaccharide (LPS). Microglia phagocytosis level was assessed by a fluorescent microsphere phagocytosis assay. PD mouse model was prepared by nigral stereotaxic injection of recombinant adeno-associated virus vector carrying human α-synuclein (α-syn). The changes in the motor behavior of the mice with both genotypes were evaluated by cylinder test, open field test, and rotarod test. Immunohistochemical staining was used to assess the loss of dopamine neurons in substantia nigra. Immunofluorescence staining was used to detect the expression level of CD68 (a key molecule involved in phagocytosis) in microglia. The results showed that CD200R1 deletion markedly enhanced LPS-induced phagocytosis in vitro by the microglial cells. In the mouse model of PD, CD200R1 deletion exacerbated motor behavior impairment and dopamine neuron loss in substantia nigra. Fluorescence intensity analysis results revealed a significant increase in CD68 expression in microglia located in the substantia nigra of CD200R1^-/- mice. The above results suggest that CD200R1 deletion may further activates microglia by promoting microglial phagocytosis, leading to increased loss of the nigrostriatal dopamine neurons in the PD model mice. Therefore, targeting CD200R1 could potentially serve as a novel therapeutic target for the treatment of early-stage PD.
Animals ; Microglia/physiology* ; Mice ; Phagocytosis ; Parkinson Disease/genetics* ; Disease Models, Animal ; Receptors, Cell Surface/physiology* ; Dopaminergic Neurons/pathology* ; Antigens, CD/metabolism* ; Gene Deletion ; Substantia Nigra ; Mice, Inbred C57BL ; Mice, Knockout ; Cells, Cultured ; Male ; alpha-Synuclein ; CD68 Molecule ; Orexin Receptors

Intelligence encompasses various abilities, including logical reasoning, comprehension, self-awareness, learning, planning, creativity, and problem-solving. Extensive research and practical experience suggest that there are sex differences in intellectual development, with females typically maturing earlier than males. However, the key genes and molecular network mechanisms underlying these sex differences in intellectual development remain unclear. To date, Genome-Wide Association Studies (GWAS) have identified 507 genes that are significantly associated with intelligence. This study first analyzed RNA sequencing data from different stages of brain development (from BrainSpan), revealing that during the late embryonic stage, the average expression levels of intelligence-related genes are higher in males than in females, while the opposite is observed during puberty. This study further constructed interaction networks of intelligence-related genes with sex-differential expression in the brain, including the prenatal male network (HELP-M: intelligence genes with higher expression levels in prenatal males) and the pubertal female network (HELP-F: intelligence genes with higher expression levels in pubertal females). The findings indicate that the key genes in both networks are Ep300 and Ctnnb1. Specifically, Ep300 regulates the transcription of 53 genes in both HELP-M and HELP-F, while Ctnnb1 regulates the transcription of 45 genes. Ctnnb1 plays a more prominent role in HELP-M, while Ep300 is more crucial in HELP-F. Finally, this study conducted sequencing validation on rats at different developmental stages, and the results indicated that in the prefrontal cortex of female rats during adolescence, the expression levels of the intelligence genes in HELP-F, as well as key genes Ep300 and Ctnnb1, were higher than those in male rats. These genes were also involved in neurodevelopment-related biological processes. The findings reveal a sex-differentiated intelligence gene network and its key genes, which exhibit varying expression levels during the neurodevelopmental process.
Female ; Intelligence/physiology* ; Male ; Sex Characteristics ; Animals ; Brain/growth & development* ; E1A-Associated p300 Protein/physiology* ; beta Catenin/physiology* ; Transcriptome ; Rats ; Gene Expression Profiling ; Genome-Wide Association Study

In order to clarify the effects of drought stress training on the quality and drought resistance of Codonopsis pilosula, this study used PEG to simulate drought stress and employed potting with water control for the drought stress training of C. pilosula plants. The polysaccharide content, secondary metabolites, antioxidant system, and photosynthetic pigment system of C. pilosula after drought stress training were analyzed. The results showed that the content of fructans in the root of C. pilosula increased after two rounds of drought stress treatment, and it was significantly higher than that of the control group. The accumulation of fructans in the root of C. pilosula showed an upward trend during the rehydration treatment. The content of lobetyolin and tangshenoside Ⅰ increased after drought stress treatment compared with that of the control group. The rehydration treatment caused first increasing and then decreasing in the content of lobetyolin, while it had no significant effect on the tangshenoside Ⅰcontent. The content of photosynthetic pigments decreased after drought stress treatment, and it gradually increased during the first round of rehydration and the second round of rehydration. Moreover, the increase was faster in the second round of rehydration than in the first round of rehydration. The content of the peroxidation product malondialdehyde(MDA) and the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) increased after drought stress treatment compared with those of the control group, and they showed a tendency of decreasing during rehydration. Moreover, the decrease was faster in the second round of rehydration than in the first round of rehydration. When the plants of C. pilosula after drought stress training were again subjected to severe drought stress, the wilting rate decreased significantly, and the biomass increases significantly. This study showed that the drought stress training could promote the accumulation of polysaccharides and secondary metabolites in the root of C. pilosula. When encountering drought stress again, C. pilosula plants could quickly regulate the antioxidant system and delay the decomposition of chlorophyll to respond to drought stress. The findings provide a theoretical basis for the ecological cultivation of C. pilosula in arid and semi-arid areas.
Codonopsis/growth & development* ; Droughts ; Polysaccharides/metabolism* ; Stress, Physiological ; Water/metabolism* ; Antioxidants/metabolism* ; Photosynthesis ; Drought Resistance