This study aims to investigate the effects of aged male parents on the learning ability of offspring and the intervention effect of Wuzi Yanzong Pills based on the microRNA-34a-5p (miR-34a-5p)/silent information regulator 1 (SIRT1) signaling pathway. Thirty-two SD male rats of 15 months old were randomized into aged model, model+high-dose (8 g·kg^-1) Wuzi Yanzong Pills, model+low-dose (2 g·kg^-1) Wuzi Yanzong Pills, and model+vitamin C (100 mg·kg^-1) groups (n=8). In addition, 8 SD male rats of 3 months old were selected as the control group. Rats in treatment groups were fed the diets containing different doses of Wuzi Yanzong Pills or vitamin C, and the control and model groups received a regular diet for 12 weeks. After 5 days of co-caging with 3-month-old female mice, the fertilization rate was recorded. An automated sperm analyzer was used to examine the sperm motility and count, and the testicular spermatogenesis was assessed by hematoxylin-eosin staining. The senescence cells in the testicular tissue was detected byβ-galactosidase staining, and miR-34a-5p expression was quantified via qPCR. The litter size was counted, and the body mass and body length were measured on days 1 and 30 to assess offspring development. For the offspring of 30 days old, their learning ability was examined via Morris water maze, and Nissl staining was employed to count hippocampal neurons. The miR-34a-5p expression in the hippocampal tissue of the offspring was determined by qPCR, and the protein levels of brain-derived neurotrophic factor (BDNF) and SIRT1 were determined by Western blot. Compared with the control group, the model group exhibited reductions in fertility rate, litter size, and sperm motility and count, as well as impaired testicular spermatogenesis (P<0.01). In addition, the model group showed increased senescence cells in testicular and epididymal tissue, accompanied by elevated miR-34a-5p expression in sperms. The 30-day-old offspring showed slow growth, reduced hippocampal neurons, up-regulated miR-34a-5p expression, and down-regulated protein levels of SIRT1 and BDNF in the hippocampus (P<0.01), along with impaired learning and memory performance (P<0.01). Compared with the model group, both high-dose Wuzi Yanzong Pills and vitamin C improved the fertilization rate, litter size, sperm motility, sperm count, and testicular spermatogenesis (P<0.05). The 30-day-old offspring in the two groups showed accelerated growth and development, increased hippocampal neurons, and elevated BDNF protein level in the hippocampus (P<0.05), along with enhanced learning and memory capabilities (P<0.05). Compared with the vitamin C group, the high-dose Wuzi Yanzong Pills group exhibited accelerated offspring growth (P<0.05), increases in fertilization rate and litter size (P<0.05), and improved learning and memory abilities (P<0.05). These findings indicate that Wuzi Yanzong Pills can improve testicular spermatogenesis and sperm quality in aged rats, thereby enhancing offspring's learning and memory performance. Specifically, Wuzi Yanzong Pills regulate miR-34a-5p expression to delay spermatogenic cell senescence in the testicular tissue and improve the offspring's cognitive function by miR-34a-5p mediated intergenerational transmission.

Focused on the challenges in brain disease treatment and advancements in nose-to-brain delivery research, this article summarized current progress in nasal drug delivery research and proposed several novel evaluation models for nasal drug absorption. By reviewing five types of evaluation models-ex vivo animal tissue models, in situ perfusion models, in vivo pharmacokinetic models, in vitro cell models, and computational fluid dynamics model-it clarified the distinct advantages of nasal drug delivery compared to other administration routes. Furthermore, by outlining emerging nasal drug delivery technologies and irritation evaluation methods, it explored the cutting-edge directions of nose-to-brain delivery. This provides essential support for the selection of nose-to-brain delivery dosage forms and paves new paths for the advancement of nasal drug delivery.

Based on supramolecular chemistry of TCM, this study investigated the interaction between Cinnamomi Cortex-Coptidis Rhizoma herb pair and compared phase states and bioactivity differences under different decoction methods (co-decoction vs individual decoction followed by mechanical mixing). Phase state variations were observed macroscopically and through turbidimetry. The herb interaction was analyzed using isothermal titration calorimetry, UV and IR spectroscopy. Particle size differences were determined by dynamic light scattering and scanning electron microscopy (SEM). Antimicrobial activity was evaluated through broth dilution, plate coating, live/dead staining, and SEM. Component analysis was conducted using UPLC-MS/MS. Results revealed distinct supramolecular structures in Cinnamomi Cortex-Coptidis Rhizoma decoctions, with co-decoction showing more stable macroscopic phase states. The interaction was a spontaneous exothermic reaction driven by both entropy and enthalpy. UV and IR spectra revealed co-decoction demonstrated more sufficient molecular interactions, more stable supramolecular structures, and smaller particle sizes with a more centralized distribution. In addition, co-decoction resulted in higher berberine and coptisine content and stronger inhibitory activity against Staphylococcus aureus compared to mechanical mixtures. These findings indicated that co-decoction produced Cinnamomi Cortex-Coptidis Rhizoma supramolecular systems with more homogeneous phase states, enhanced measurable coptisine and berberine content, and superior antibacterial efficacy.

Using the whole-genome data of Atractylodes lancea, members of the auxin (Aux)/indole-3-acetic acid (IAA) gene family were identified and characterized, and the effects of 1-naphthaleneacetic acid (NAA) treatment on the expression levels of this gene family were investigated, providing a foundation for further studies on the functions of the A. lancea Aux (AlAux)/IAA gene family. Members of the AlAux/IAA gene family were identified from the A. lancea whole-genome data using TBtools-Ⅱ. Bioinformatics software was employed to analyze the physicochemical properties of the encoded proteins, construct a phylogenetic tree, and predict conserved motifs and gene structures. Tissue-cultured seedlings of A. lancea were used as experimental materials, and key genes of the AlAux/IAA gene family were screened by transcriptome sequencing. The expression of key AlAux/IAA genes was analyzed after one month of NAA treatment. A total of 53 AlAux/IAA genes were identified from the A. lancea genome. Most AlAux/IAA proteins were localized in the nucleus, lacked transmembrane domains, and exhibited negative hydrophobicity. Among them, 44 AlAux/IAA genes were predicted to encode functional Aux/IAA transport proteins. Transcriptome sequencing and RT-qPCR analyses showed that the AlAux/IAA family genes exhibited spatiotemporal expression specificity, and different members displayed varying response times and intensities to NAA treatment. Tissue-specific expression analysis revealed that the AlAux/IAA gene family was generally highly expressed in flowers. This study identified the Aux/IAA gene family members in A. lancea, preliminarily analyzed their sequence characteristics, and examined their expression features in response to Aux. It is speculated that AlAux/IAA13 and AlAux/IAA38 may be involved in rooting and bud growth and development during the subculture process of A. lancea tissue-cultured seedlings. These results provide a theoretical basis for elucidating the molecular mechanisms of AlAux/IAA gene function and Aux-mediated regulation of rhizome growth in A. lancea.

This study investigated the effects and molecular mechanisms of sarsasapogenin (SSG) on colorectal cancer (CRC). After HRT-18 and HCT116 cells were treated with varying concentrations of SSG, the effect of SSG on CRC cell proliferation, migration, and glycolysis was assessed by cell counting kit-8 (CCK-8), real-time cellular analysis (RTCA), colony formation assay, high-content imaging analysis, and Seahorse glycolysis stress test. Changes in intracellular lactate release and adenosine triphosphate (ATP) levels under SSG treatment were measured by lactate and ATP detection kits, respectively. The effects of SSG on the transcription level and protein expression of the key glycolytic gene hypoxia-inducible factor 1α (HIF1α) were evaluated via quantitative polymerase chain reaction (qPCR) and Western blot. Direct binding between SSG and HIF1α was identified by drug affinity responsive target stability (DARTS). The UbiBrowser database, microscale thermophoresis (MST), and molecular docking simulations were employed to screen and validate the E3 ubiquitin ligase mediating HIF1α degradation. The results showed that SSG significantly inhibited CRC cell proliferation and colony formation in a dose-dependent manner. The 24-hour half-maximal inhibitory concentrations (IC₅₀) of SSG for HRT-18 and HCT116 cells were 6.275 μmol·L^-1 and 7.029 μmol·L^-1, respectively. After 24 hours of treatment with SSG at concentrations of 2.0, 4.0, and 6.0 μmol·L^-1, the HRT-18 and HCT116 clone formation rate was significantly reduced. High-content imaging results showed that SSG significantly inhibited the migration ability of CRC cells. Seahorse glycolysis stress test, along with lactate and ATP measurements, demonstrated that SSG suppressed basal glycolysis, glycolytic capacity, glycolytic reserve, lactate release, and ATP content in CRC cells. The qPCR and Western blot results showed that SSG had no significant effect on HIF1α mRNA expression, and the HIF1α protein expression was downregulated. DARTS confirmed the direct binding of SSG to HIF1α. UbiBrowser analysis identified five E3 ubiquitin ligases potentially targeting HIF1α. Molecular docking and MST results indicated that the F-box/WD repeat-containing protein 7 (FBXW7) exhibited strong binding affinity to HIF1α in the presence of SSG. In summary, SSG exerts its anti-cancer effects in CRC by targeting HIF1α to promote its FBXW7-mediated proteasomal degradation and consequently inhibiting glycolytic reprogramming.

This study investigated the toxicological mechanisms of different processed products of Strychnos nux-vomica seeds using serum metabolomics analysis. Seventy-two female KM mice were randomly divided into six groups (n = 12 per group): control, raw seeds, vinegar-processed seeds, urine-soaked seeds, sand-roasted seeds, and oil-fried seeds. Each processed preparation group received an aqueous decoction of the original herb at the same concentration for 7 days. Hepatic and renal coefficients were measured in each group, and the levels of hepatic and renal injury markers, including aspartate transaminase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and creatinine (CRE) were determined using a fully automated biochemical analyzer. Hematoxylin-eosin (HE) staining was used for histopathological examination of the liver and kidney. Liquid chromatography-mass spectrometry (LC-MS/MS) combined with multivariate statistical analysis was employed to screen for differential serum metabolites across groups. Metabolic pathway enrichment analysis of the selected differential markers was performed using the Human Metabolome Database (HMDB) and MetaboAnalyst 6.0. All processed S. nux-vomica seed products increased hepatic and renal coefficients and elevated hepatic and renal injury markers (AST, ALT, BUN, CRE), although these effects were reduced to varying degrees compared to the raw product. Overall, vinegar processing exhibited the most significant detoxification effect, followed by oil-fried>sand-roasted≈urine-soaked > raw seeds. Metabolomic analysis identified 14 differential metabolites across the groups, primarily including sphingolipids, glycerophospholipids, and vitamin-related compounds. Five significantly perturbed metabolic pathways were identified: sphingolipid metabolism, glycerophospholipid metabolism, α-linolenic acid metabolism, lipoic acid metabolism, and linoleic acid metabolism, with sphingolipid and glycerophospholipid metabolism common to all groups. In conclusion, processing of S. nux-vomica seeds reduced hepatorenal toxicity to varying degrees, and its toxic mechanisms may primarily involve disturbances in sphingolipid and glycerophospholipid metabolism.

Osteoarthritis (OA) is a common degenerative joint disease characterized by cartilage degeneration, synovial inflammation, osteophyte formation, and joint space narrowing, seriously impairing patients' mobility and quality of life. The pathogenesis of OA is highly complex, involving multiple cell types and signaling pathways. Key pathological processes include abnormal chondrocyte function, sustained activation of inflammatory responses, and imbalances in apoptosis and autophagy. In recent years, microRNAs (miRNAs), small non-coding RNAs, have been recognized for their crucial roles in regulating gene expression and influencing the progression of various diseases. miRNAs exhibit important regulatory functions in OA-related processes such as inflammatory regulation, chondrocyte apoptosis and autophagy, extracellular matrix metabolism, and subchondral bone remodeling. Multiple specific miRNAs have been shown to be closely associated with the onset and progression of OA, demonstrating potential diagnostic and therapeutic value. Traditional Chinese medicine (TCM) is an important treatment approach for OA, offering advantages such as multi-component, multi-target, and multi-pathway regulation. Recent studies have shown that TCM single herbs, compound prescriptions, acupuncture, and moxibustion can upregulate or downregulate the expression of specific miRNAs, thereby intervening in their downstream target genes and related signaling pathways. This leads to anti-inflammatory and analgesic effects, inhibition of chondrocyte apoptosis, promotion of matrix synthesis, and cartilage repair. This review systematically summarizes the mechanisms of miRNAs in the progression of OA, with a focus on the latest research advances in TCM regulation of miRNAs to intervene in OA. The aim is to provide a theoretical basis and new insights for the early molecular diagnosis, targeted therapy, and modern research and clinical translation of TCM in OA.

This study aims to compare the efficacy and safety of different traditional Chinese medicine injections (TCMIs) combined with conventional western medicine in the treatment of chronic obstructive pulmonary disease (COPD) with respiratory failure (RF) using a network Meta-analysis approach. A comprehensive literature search was conducted in CNKI, VIP, Wanfang, SinoMed, Web of Science, PubMed, Cochrane Library, and EMbase databases from inception to June 29, 2025. Randomized controlled trials (RCTs) were performed by employing the literature on the treatment of COPD with RF by TCMIs, and data were analyzed by Stata 17. A total of 110 RCTs involving 9 218 participants and 11 different TCMIs were included. The ranking of efficacy in the surface under the cumulative ranking curve (SUCRA) from network Meta-analysis was as follows: ① for improving clinical total response rate, Chuanxiongqin Injection + conventional western medicine, Shankezhi Injection + conventional western medicine, and Danhong Injection + conventional western medicine ranked top three; ② for reducing mortality, Chuanxiongqin Injection + conventional western medicine, Danshen Chuanxiongqin Injection + conventional western medicine, and Shenfu Injection + conventional western medicine ranked top three; ③ for shortening length of hospital stay, Danshen Chuanxiongqin Injection + conventional western medicine, Shenfu Injection + conventional western medicine, and Shenmai Injection + conventional western medicine ranked top three; ④ for reducing duration of mechanical ventilation, Shenqi Fuzheng Injection + conventional western medicine, Shenmai Injection + conventional western medicine, and Tanreqing Injection + conventional western medicine ranked top three; ⑤ for improving arterial partial pressure of oxygen (PaO₂), Chuanxiongqin Injection + conventional western medicine, Danshen Injection + conventional western medicine, and Danhong Injection + conventional western medicine ranked top three; ⑥ for reducing arterial partial pressure of carbon dioxide (PaCO₂), Shenfu Injection + conventional western medicine, Tanreqing Injection + conventional western medicine, and Danshen Chuanxiongqin Injection + conventional western medicine ranked top three; ⑦ for improving arterial oxygen saturation (SaO₂), Shenqi Fuzheng Injection + conventional western medicine, Xuebijing Injection + conventional western medicine, and Xingnaojing Injection +conventional western medicine ranked top three; ⑧ for improving forced expiratory volume in one second (FEV₁), Chuanxiongqin Injection + conventional western medicine, Shenmai Injection + conventional western medicine, and Tanreqing Injection + conventional western medicine ranked top three; ⑨ for improving forced vital capacity (FVC), Danshen Chuanxiongqin Injection + conventional western medicine, Xuebijing Injection + conventional western medicine, and Tanreqing Injection + conventional western medicine ranked top three. In terms of safety, adverse events were mostly mild and occurred at a low incidence. In conclusion, TCMIs combined with conventional western medicine may offer clinical benefits in the management of COPD with RF. However, due to limitations in the number and quality of studies for each intervention, further rigorously designed RCT should be conducted to validate these findings.

Clarifying the two-dimensional spatial distribution and the seasonal yield dynamics of Epimedium pubescens roots in agroforestry systems can provide an ecological theoretical basis and technical support for optimizing the understory cultivation patterns of E. pubescens. E. pubescens plants cultivated in Ginkgo biloba forests (YX), Phellodendron amurense forests (HB), and monocropping fields (CK) were taken as research subjects. Stratified sampling was conducted during the summer and winter harvest seasons to analyze root spatial distribution, morphological characteristics, and biomass allocation. Additionally, high-performance liquid chromatography (HPLC) was employed to determine the total flavonol glycoside content. The results demonstrated that the spatial distribution of E. pubescens roots exhibited significant differences among planting patterns. Specifically, the HB group showed a significantly higher proportion of fine roots in the surface soil layer (0-10 cm) than the YX and CK groups, whereas the YX group displayed more extensive root distribution in deeper soil layers (30-50 cm) than the HB and CK groups. The root morphology of E. pubescens was significantly influenced by planting patterns and seasonal variations. In summer, the root length density of E. pubescens in the YX group decreased by 56%-75% (P<0.05) in the 0-20 cm soil layer compared with that in the CK group, whereas in winter, both agroforestry systems showed significantly higher root length density than the CK group. No significant difference was observed in aboveground or belowground biomass of E. pubescens among different planting patterns. However, the YX group exhibited significantly higher root biomass allocation ratio and significantly lower rhizome biomass allocation ratio than the CK and HB groups. These findings indicate that E. pubescens roots exhibit remarkable phenotypic plasticity, enabling adaptive adjustment strategies to enhance resource acquisition efficiency in agroforestry systems.

Colorectal cancer (CRC) is a highly prevalent malignant tumor worldwide, and its occurrence and development are closely related to gut microbiota disturbance. The germ-free (GF) animal model, by providing a unique environment free of indigenous microorganisms, has become a tool for precisely dissecting the causal role and mechanism of the gut microbiota in the occurrence and development of CRC and the therapeutic mechanisms of pharmaceuticals. This review aims to systematically elaborate on the application progress of GF animal models in CRC research, with a focus on the key mechanisms by which specific microorganisms promote the occurrence and development of CRC revealed by this model. Furthermore, this review focuses on the research dynamics of TCM in this field and systematically expounds the application of GF models in the research of TCM against CRC. Through in-depth analysis of the GF animal models of CRC, it is possible to develop precise diagnostic and therapeutic strategies based on TCM and the microbiome in the future, providing new directions and ideas for the prevention and treatment of CRC.