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.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective To evaluate the predictive value of a dose-surface histogram (DSH) for radiation cystitis (RC) in patients with cervical cancer. Methods We retrospectively included 190 patients with cervical cancer who underwent image-guided radiotherapy (IGRT) from the HIS system of The First Affiliated Hospital of Hebei North University from May 2013 to May 2023. The patients were divided into test group (n = 100) and control group (n = 90). The dose distribution in the bladder was evaluated by using a DSH for the test group and using a dose-volume histogram (DVH) for the control group. Receiver operating characteristic curves were used to evaluate the predictive value of DSH for RC in comparison with DVH. Results There were no significant differences in baseline data and RC incidence between the two groups (all P＞0.05). All evaluation indicators were significantly different between DSH and DVH (all P＜0.05). The predictive value of S₄₅ and V₄₅ for the incidence of grade-I, -II, and -III RC was low (all P＜0.05). The predictive value of S₅₀ and V₅₀ for the incidence of grade-I, -II, and -III RC was moderate (all P＜0.05). S₅₅−S₅₇ and V₅₅−V₅₇ showed high value for predicting the incidence of grade-I, -II, and -III RC (all P＜0.05). Conclusion DSH shows basically the same predictive value for the incidence of RC caused by IGRT in cervical cancer as DVH, which is expected to become a new tool for evaluating radiotherapy plans.

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

MADS-box protein family are important transcriptional regulatory factors in plant growth and development. The AGAMOUS 12 (AGL12) subfamily is believed to play an important regulatory role in the process of plant flowering transition. To explore the potential mechanism of AGL12 subfamily involved in regulating the flower development of Lonicera macranthoides, quantitative real-time polymerase chain reaction (qRT-PCR), prokaryotic expression and yeast two-hybrid techniques were used to analyze the expression pattern, protein expression, and protein-protein interaction pattern of LmAGL12 based on transcriptome data. The results showed that the LmAGL12 gene contains a 603 bp open reading frame (ORF), encoding 200 amino acids, and the encoded protein was stable and hydrophilic without a transmembrane region and signal peptide. Through homologous sequence alignment and phylogenetic analysis, it was confirmed that LmAGL12 protein belongs to the MADS-box protein family and is closely related to the AGL12 protein of Heracleum sosnowskyi and Daucus carota subsp. sativus. The LmAGL12 gene was cloned into prokaryotic expression vector pET-28a and the recombinant constructs were transformed into Escherichia coli BL21 (DE3), which inducing the target protein successfully. The yeast two-hybrid results showed that LmAGL12 protein interacts with LmSVP protein, LmSOC1 protein and LmAP1 protein, respectively. The qRT-PCR results showed that LmAGL12 gene were differentially expressed in different development stages of flower bud, stem, and leaves of 'Longhua' and 'Baiyun' in L. macranthoides. The LmAGL12 gene showed the highest expression level in the middle stage of the 'Longhua' floral bud; For the 'Baiyun' variety, the relative expression level of LmAGL12 gene is the highest in the stem. This study cloned the LmAGL12 gene in L. macranthoides and analyzed it expression for the first time, enriching the research on flower organ development and providing a research basis for further exploring the molecular mechanisms of long bud stage and non-unfolded corolla in L. macranthoides, as well as for variety improvement.

Objective To analyze the effect of fisetin against venous thrombosis in rats.Methods Seventy SD rats were randomly divided into the following groups:sham-operation group,model group,fisetin 45 mg/kg,15 mg/kg,5 mg/kg groups,and aspirin group(47 mg/kg).The corresponding medication was administered by gavage once a day consecutively(the sham-operation group and the model group were given 0.5％carboxymethyl cellulose sodium solution with 10 mL/kg,respectively)for 7 consecutive days.One hour after the last administration,the rats were anesthetized,the lower part of the intersection of inferior vena cava and left renal vein was ligated with silk thread(no ligation in the sham-operation group),and the abdominal wall was sutured.Two hours later,the abdominal cavity was reopened,the other venous branches 1.5 cm away from the ligation site were closed with the artery clamp,and blood was collected from the abdominal aorta.The anticoagulant ratio of 3.8％sodium citrate∶whole blood was 1∶9.The venous thrombus 1 cm down from the ligation point of the intersection of inferior vena cava and left renal vein was cut and the thrombus was separated.The residual blood was dried with filter paper,weighed and recorded.Plasma was taken after anticoagulant blood centrifugation.The levels of plasma antithrombin-Ⅲ(AT-Ⅲ),protease C(PC),plasminogen(PLG),and plasminogen activator inhibitor(PAI-1)were detected by ELISA kits.Results Compared with the model group,the weight of thrombus in fisetin 45 mg/kg group and aspirin 47 mg/kg group decreased(P＜0.01).The content of AT-Ⅲ in three fisetin groups increased(all P＜0.05).The content of PC in fisetin 45 mg/kg increased(P＜0.05).The content of PLG and PAI-1 in fisetin 45 mg/kg group decreased(both P＜0.05).Conclusion Fisetin has the effect against venous thrombosis in vivo,and the effect is related to the upregulation of AT-Ⅲ and PC and the downregulation of PLG and PAI-1.

ObjectiveExosomes are microvesicles which could be secreted by all cell types with diameters between 30 and 150 nm. It was widely distributed in body fluids including blood, urine, and breast milk. Exosomes are considered as potential biomarkers and drug carriers by reason of containing nucleic acids, lipids, proteins and other bioactive molecules. Milk-derived exosomes have been widely used as drug delivery carriers to treat targeted diseases with a lower cost, higher biocompatibility and lower immunogenicity. Until now, there is no research about the milk-derived exosomes phosphorylation to reveal the difference of protein phosphorylation in different species of milk. To investigate the pathways and proteins with specific functions, phosphorylated proteomic analysis of milk-derived exosomes from different species is performed, and provide new ideas for exploring diversified treatments of disease. MethodsWhey and exosomes derived from bovine, porcine and caprine milk were performed for proteomics and phosphoproteomics analysis. The relationship between milk exosome proteins from different species and signaling pathways were analyzed using bioinformatics tools. ResultsA total of 4 191 global proteins, 1 640 phosphoproteins and 4 064 phosphosites were identified from 3 species of milk-derived exosomes, and the exosome proteins and phosphoproteins from different species were significantly higher than those of whey. Meanwhile, some special pathways were enriched like Fcγ-mediated phagocytosis from bovine exosomes, pathways related with neural and immune system from caprine exosomes, positive and negative regulation of multiple activities from porcine exosomes. ConclusionIn this study, the proteomic and phosphoproteomic analyses of exosomes and whey from bovine, porcine and caprine milk were carried out to reveal the difference of composition and related signaling pathways of milk exosome from different species. These results provided powerful support for the application of exosomes from different milk sources in the field of disease treatment.

The MADS-box gene family is a very important transcriptional regulator gene, which plays a role in the whole growth and development process of plants. The APETALA1 (AP1) gene is considered to play an important regulatory role in the transformation of plant flowering, but also to control the characteristic development of floral organs. Lonicera macranthoides is used as medicine with dry buds and early flowers. Therefore, studying the potential mechanism of AP1 gene in regulating flower organ development can provide a basis for improving its medicinal value by molecular means. To explore the potential mechanism of the AP1 gene in the regulation of floral organ development in L. macranthoides, the full-length cDNA of the AP1 was cloned by reverse transcription PCR (RT-PCR) and named LmMADS4. The results show that the CDS of the LmMADS4 gene is 729 bp and encodes 242 amino acids, and the LmMADS4 protein contains no signal peptide and no transmembrane structure, which is an unstable hydrophilic protein. Through homologous sequence alignment and phylogenetic analysis, LmMADS4 and L. japonica MADS27 protein cluster into one class and are closely related. Finally, the expression pattern and protein interaction pattern of LmMADS4 were analyzed by real-time reverse transcription-PCR (qRT-PCR) and yeast two-hybrid technology. The qRT-PCR showed that LmMADS4 gene was differentially expressed in the stems, leaves and flower bud at different developmental stages, including bud type variety Longhua and common variety Baiyun; and LmMADS4 gene was highly expressed in the flower buds, and with the development of flower buds, LmMADS4 gene was continuously up-regulated in the flower bud variety Longhua, however, the expression level of LmMADS4 in the Baiyun terminal flower bud was lower than that in the late flower bud, but the difference was not significant. The yeast two-hybrid results showed that the bait vector pGBKT7-LmMADS4 was not toxic to yeast strains and had no self-activating activity. LmMADS4 protein interacted with LmSVP1, LmSVP3 and LmSOC1s proteins. This study can provide a theoretical basis for exploring the mechanism of long flower bud stage and corolla non-unfolding at the molecular level and variety improvement of L. macranthoides.

Objective To investigate the effect of XUE Ji's morning-evening supplementing method,a therapy by tonification according to the alteration of daily yang-qi in the human body and the nature proposed by practitioner XUE Ji in Ming Dynasty,combined with Seretide on exercise endurance in patients with stable chronic obstructive pulmonary disease(COPD)of lung and kidney deficiency type.Methods Ninety-two patients with stable COPD of lung and kidney deficiency type were randomly divided into treatment group and control group,with 46 cases in each group.The control group was given inhalation of Salmeterol/Fluticasone Inhalation Powder(Seretide),and the treatment group was treated with Buzhong Yiqi Pills in the morning and Liuwei Dihuang Pills at evening on the basis treatment for the control group.The course of treatment covered 3 months.The changes of the scale scores of traditional Chinese medicine(TCM)syndrome and St Georges respiratory questionnaire(SGRQ)for quality of life,the distance of 6-minute walking test(6MWT)for exercise endurance,and pulmonary function indicators of forced expiratory volume in one second(FEV1),forced vital capacity(FVC)and their ratio(FEV1/FVC)in the two groups before and after treatment were observed.After treatment,the clinical efficacy and the incidence of adverse reactions were compared between the two groups.Results(1)During the trial,a total of 3 cases were lost,and a total of 89 patients were eventually included,including 45 cases in the treatment group and 44 cases in the control group.(2)After 3 months of treatment,the total effective rate of the treatment group was 82.22％(37/45),and that of the control group was 72.73％(32/44).The intergroup comparison by chi-square test showed that the efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the scores of TCM syndromes in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the decrease in the treatment group was more significant than that in the control group(P＜0.01).(4)After treatment,the lung function indicators of FEV1,FVC and FEV1/FVC in the two groups were significantly improved compared with those before treatment(P＜0.05),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the scores of SGRQ items of respiratory symptoms,disease impact and activity limitation in the two groups were significantly lower than those before treatment(P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group,the differences being statistically significant(P＜0.01).(6)After treatment,the 6MWT distance of the two groups was significantly improved compared with that before treatment(P＜0.01),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.01).(7)During the treatment,no abnormal changes in the indicators of blood routine test,liver and kidney function,electrocardiogram,and urine and stool routine were found in the two groups.Conclusion XUE Ji's morning-evening supplementing method combined with Seretide exert certain effect in treating stable COPD patients with lung and kidney deficiency syndrome.The therapy can effectively alleviate the clinical symptoms ofnd improve the lung function,exercise endurance and quality of life of the patients,with high safety.

Objective:To observe the effects of moxibustion on the levels of glucose-6-phosphate dehydrogenase(G6PD)and reduced nicotinamide adenine dinucleotide phosphate(NADPH)in the plasma and spleen and the CD4+T-cell number in the spleen of rats with adjuvant arthritis,thus to explore the mechanism in rheumatoid arthritis(RA)treatment with moxibustion by regulating the CD4+T-cell proliferation through G6PD-mediated pentose phosphate pathway. Methods:Twenty-seven male Sprague-Dawley rats were randomly divided into a blank group,a model group,and a moxibustion group,with 9 rats in each group.Incomplete Freund's adjuvant was used to induce inflammation in the model group and the moxibustion group.The blank group and the model group were not intervened.In the moxibustion group,suspended moxibustion was performed at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 30 min,once a day for 24 times in total.Hematoxylin-eosin staining was used to evaluate the histopathological changes of rat synovial tissue;the swelling degree of the rat toes was observed by measuring the toe volume;G6PD and NADPH in the spleen and plasma were detected by Western blotting and enzyme-linked immunosorbent assay.Flow cytometry was used to detect the CD4+T-cell number in the spleen. Results:Compared with the blank group,the levels of G6PD and NADPH in the plasma and spleen and the CD4+T-cell number in the spleen were significantly increased in the model group(P<0.01 or P<0.05).Compared with the model group,the NADPH level in the spleen and plasma and the CD4+T-cell number in the spleen in the moxibustion group decreased significantly(P<0.05 or P<0.01),and the G6PD level in the plasma decreased significantly(P<0.05),but there was no significant difference in the G6PD level in the spleen(P>0.05). Conclusion:Moxibustion can regulate immunity and improve joint synovial inflammation in RA.The mechanism may be that the G6PD-mediated pentose phosphate pathway reduces the production of metabolite NAPDH in CD4+T cells,thereby inhibiting the proliferation of naive CD4+T cells.