Garcinol, a benzenetriol compound extracted from Garcinia cambogia, has antitumor activity, however, its antitumor mechanism remains unclear. The aim of this study was to investigate the role and mechanism of garcinol as a novel potential proteasome inhibitor. We applied the drug affinity responsive target stability (DARTS) method coupled to mass spectrometry to determine the binding protein of garcinol; the proteasome activity assay was used to determine the effect of garcinol on its hydrolase activity; immunofluorescence and proximity ligation assay (PLA) were used to detect the effects of garcinol on ubiquitin and RPN6; and flow cytometry were used to determine the effects of garcinol on cell apoptosis; and the anti-cancer effect was studied in organoid models. The results showed that RPN6 was a direct binding protein of garcinol; garcinol inhibited the hydrolase activity of proteasome, and induced the accumulation and aggregation of ubiquitin protein, and its proteasomal inhibitory effect was dependent on RPN6; further studies showed that garcinol induced oligomerization of RPN6 and formation of granules in the nucleus; finally, it was verified that garcinol induced apoptosis of tumor cells, and inhibited the growth of organoids of Apc^min/+ small intestine mice. These results suggest that garcinol is a potential proteasome inhibitor, which inhibits proteasome activity by directly targeting RPN6 on proteasome 19S, which in turn induces cell apoptosis and inhibits tumor growth.

The innate immune system detects cellular stressors and microbial infections, activating programmed cell death (PCD) pathways to eliminate intracellular pathogens and maintain homeostasis. Among these pathways, pyroptosis, apoptosis, and necroptosis represent the most characteristic forms of PCD. Although initially regarded as mechanistically distinct, emerging research has revealed significant crosstalk among their signaling cascades. Consequently, the concept of PANoptosis has been proposed—an inflammatory cell death pathway driven by caspases and receptor-interacting protein kinases (RIPKs), and regulated by the PANoptosome, which integrates key features of pyroptosis, apoptosis, and necroptosis. The core mechanism of PANoptosis involves the assembly and activation of the PANoptosome, a macromolecular complex composed of three structural components: sensor proteins, adaptor proteins, and effector proteins. Sensors detect upstream stimuli and transmit signals downstream, recruiting critical molecules via adaptors to form a molecular scaffold. This scaffold activates effectors, triggering intracellular signaling cascades that culminate in PANoptosis. The PANoptosome is regulated by upstream molecules such as interferon regulatory factor 1 (IRF1), transforming growth factor beta-activated kinase 1 (TAK1), and adenosine deaminase acting on RNA 1 (ADAR1), which function as molecular switches to control PANoptosis. Targeting these switches represents a promising therapeutic strategy. Furthermore, PANoptosis is influenced by organelle functions, including those of the mitochondria, endoplasmic reticulum, and lysosomes, highlighting organelle-targeted interventions as effective regulatory approaches. Cardiovascular diseases (CVDs), the leading global cause of morbidity and mortality, are profoundly impacted by PCD. Extensive crosstalk among multiple cell death pathways in CVDs suggests a complex regulatory network. As a novel cell death modality bridging pyroptosis, apoptosis, and necroptosis, PANoptosis offers fresh insights into the complexity of cell death and provides innovative strategies for CVD treatment. This review summarizes current evidence linking PANoptosis to various CVDs, including myocardial ischemia/reperfusion injury, myocardial infarction, heart failure, arrhythmogenic cardiomyopathy, sepsis-induced cardiomyopathy, cardiotoxic injury, atherosclerosis, abdominal aortic aneurysm, thoracic aortic aneurysm and dissection, and vascular toxic injury, thereby providing critical clinical insights into CVD pathophysiology. However, the current understanding of PANoptosis in CVDs remains incomplete. First, while PANoptosis in cardiomyocytes and vascular smooth muscle cells has been implicated in CVD pathogenesis, its role in other cell types—such as vascular endothelial cells and immune cells (e.g., macrophages)—warrants further investigation. Second, although pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are known to activate the PANoptosome in infectious diseases, the stimuli driving PANoptosis in CVDs remain poorly defined. Additionally, methodological challenges persist in identifying PANoptosome assembly in CVDs and in establishing reliable PANoptosis models. Beyond the diseases discussed, PANoptosis may also play a role in viral myocarditis and diabetic cardiomyopathy, necessitating further exploration. In conclusion, elucidating the role of PANoptosis in CVDs opens new avenues for drug development. Targeting this pathway could yield transformative therapies, addressing unmet clinical needs in cardiovascular medicine.

ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome （PCOS）. MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group， and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method， the rats were divided into the following groups： normal group， model group， Xiaoyaosan group （11.97 g·kg^-1）， Sanzi Yangmo decoction group （28.35 g·kg^-1）， cyclical therapy group （11.97/28.35 g·kg^-1）， and aspirin group （8 × 10^-3 mg·kg^-1）. After 12 days of continuous administration by gavage （equivalent to three estrous cycles）， female and male rats were co-housed. On the fifth day of pregnancy， the number of blastocyst implantation in each group was counted. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of estradiol （E₂） and progesterone （P） in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor （VEGF）， progesterone receptor （PR）， estrogen receptor （ER）， androgen receptor （AR）， and integrin（ITG） αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-140-5 P， VEGF， vascular endothelial growth factor receptor 2 （VEGFR2）， PR， ER， AR， and ITGαvβ3 in rat endometrium. ResultsCompared with normal group， the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner， the number of uterine glands and blood vessels were significantly reduced （P<0.01）， and the pregnancy rate was significantly reduced. Compared with the model group， each drug group restored the regular estrous cycle to varying degrees， and the endometrial thickness and the number of blood vessels were significantly improved （P<0.01）. The pregnancy rate of each drug group increased， and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group， the levels of serum E₂ and P in the model group were significantly decreased （P<0.01）， the expression of VEGF， ER， PR and ITGαvβ3 protein was significantly decreased （P<0.05，P<0.01）， the expression of AR protein was significantly increased （P<0.01）， the expression of miR-140-5P and AR mRNA was significantly increased （P<0.01）， and the expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA was significantly decreased （P<0.01）. Compared with model group， the serum E₂ level in the Xiaoyaosan group was significantly increased （P<0.01）.The levels of E₂ and P in serum of rats in Sanzi Yangmo decoction group， cycle therapy group and aspirin group were significantly increased （P<0.01）. The expression of AR protein in each drug group was significantly decreased （P<0.01）. The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased （P<0.01）. The expression of VEGF， ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees （P<0.05，P<0.01）. The expression of VEGF， PR， ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees （P<0.05，P<0.01）. The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased （P<0.01）. The expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA in each drug group increased to varying degrees （P<0.05，P<0.01）. Compared with Xiaoyaosan group and Sanzi Yangmo decoction group， the expression of miR-140-5P， VEGFR2， ER， PR， AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different （P<0.05，P<0.01）. ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P， target the upregulation of VEGF expression， mediate angiogenesis， and promote endometrial angiogenesis， thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.

ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome （PCOS）. MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group， and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method， the rats were divided into the following groups： normal group， model group， Xiaoyaosan group （11.97 g·kg^-1）， Sanzi Yangmo decoction group （28.35 g·kg^-1）， cyclical therapy group （11.97/28.35 g·kg^-1）， and aspirin group （8 × 10^-3 mg·kg^-1）. After 12 days of continuous administration by gavage （equivalent to three estrous cycles）， female and male rats were co-housed. On the fifth day of pregnancy， the number of blastocyst implantation in each group was counted. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of estradiol （E₂） and progesterone （P） in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor （VEGF）， progesterone receptor （PR）， estrogen receptor （ER）， androgen receptor （AR）， and integrin（ITG） αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-140-5 P， VEGF， vascular endothelial growth factor receptor 2 （VEGFR2）， PR， ER， AR， and ITGαvβ3 in rat endometrium. ResultsCompared with normal group， the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner， the number of uterine glands and blood vessels were significantly reduced （P<0.01）， and the pregnancy rate was significantly reduced. Compared with the model group， each drug group restored the regular estrous cycle to varying degrees， and the endometrial thickness and the number of blood vessels were significantly improved （P<0.01）. The pregnancy rate of each drug group increased， and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group， the levels of serum E₂ and P in the model group were significantly decreased （P<0.01）， the expression of VEGF， ER， PR and ITGαvβ3 protein was significantly decreased （P<0.05，P<0.01）， the expression of AR protein was significantly increased （P<0.01）， the expression of miR-140-5P and AR mRNA was significantly increased （P<0.01）， and the expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA was significantly decreased （P<0.01）. Compared with model group， the serum E₂ level in the Xiaoyaosan group was significantly increased （P<0.01）.The levels of E₂ and P in serum of rats in Sanzi Yangmo decoction group， cycle therapy group and aspirin group were significantly increased （P<0.01）. The expression of AR protein in each drug group was significantly decreased （P<0.01）. The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased （P<0.01）. The expression of VEGF， ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees （P<0.05，P<0.01）. The expression of VEGF， PR， ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees （P<0.05，P<0.01）. The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased （P<0.01）. The expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA in each drug group increased to varying degrees （P<0.05，P<0.01）. Compared with Xiaoyaosan group and Sanzi Yangmo decoction group， the expression of miR-140-5P， VEGFR2， ER， PR， AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different （P<0.05，P<0.01）. ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P， target the upregulation of VEGF expression， mediate angiogenesis， and promote endometrial angiogenesis， thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Porcine arthritis,one of the common chronic diseases in large-scale pig farms,can signifi-cantly reduce the production performance of meat pigs.In this study,a strain of Haemophilus pa-rasuis(HPS)was isolated from the joint fluid of a lame pig.The HPS was analyzed in terms of se-rotypes,virulence genes,and resistance genes.Additionally,it was treated with sensitive antibiotics to provide a theoretical basis for the comprehensive prevention and treatment of arthritis in meat pigs in future production settings.A strain of HPS type 14 was isolated from the joint fluid of dis-eased pigs.The HPS isolate demonstrated sensitivity to β-lactams and tetracyclines,while florfeni-col and polymyxin effectively inhibited its growth at low concentrations.However,the bacteria ex-hibited resistance to sulfonamides and ciprofloxacin.The treatment of affected pigs with clinical ar-thritis using doxycycline and enrofloxacin injections proved effective.Compared to the infected group,in which the sick pigs experienced difficulty flexing their carpal and tarsal joints and exhibi-ted significant lameness,the pigs in the treatment group showed marked improvement.Their joints were only slightly swollen,and the clinical symptoms of arthropathy were alleviated.

Objective:The characteristics of D-dimer（D-D），liver enzymes and clinical presentation in pediatric Mycoplasma pneumoniae pneumonia（MPP）complicated by plastic bronchitis（PB）were analyzed,and the predictive value of abnormal D-D and liver enzymes in MPP complicated by PB was discussed.Methods:Patients diagnosed with MPP who underwent bronchoscopy at the Pediatric Department of Shenzhen Baoan Women's and Children's Hospital in Shenzhen between March 2023 and March 2024 were enrolled. The participants were categorized into the PB group and the non-PB group based on the presence or absence of PB complications.The differences in clinical characteristics，treatment characteristics，laboratory results and imaging results between the two groups were compared.The nomogram prediction model of MPP combined with PB was established,and its effectiveness was evaluated.Results:A total of 225 pediatric patients were enrolled,including 52 cases in the PB group and 173 cases in the non-PB group. No statistically significant differences were observed between the two groups in baseline characteristics such as age, gender, and body weight ( P>0.05).The PB group had a higher proportion of respiratory distress, respiratory support, PICU admission, decreased of SpO 2, viral infection and bacterial infection. And neutrophil ratio, C-reactive protein,procalcitonin, coagulation index and liver enzyme index were significantly higher than those in non-PB group.The analysis of binary Logistic analysis showed that increased aspartic transaminase, increased D-D,and the need of respiratory support were independent risk factors for MPP combined with PB.The nomogram predictive model based on binary Logistic analysis showed that the area under curve for predicting MPP combined with PB was 0.800（95% CI 0.724-0.875， P<0.001）.The calibrate curve showed that the predicted probability of the model fit well with actual probability. Conclusion:Children with MPP complicated by PB have higher levels of aspartic transaminase and D-D,along with an increased proportion requiring repiratory support.The prediction model based on these indicators shows good clinical application value.

The biosensors based on clustered regularly interspaced short palindromic repeats(CRISPR)were introduced in terms of detection strategies and advantages.The current situation of the CRISPR-based biosensors was reviewed when applied to detecting non-nucleic acid targets such as proteins,exosomes,small molecules,enzymes,hormones and antibodies.The deficiencies of the CRISPR-based biosensors were analyzed during the application,and the future development directions were envisioned.

BACKGROUND:Knee osteoarthritis is a common degenerative disease that significantly impacts patients'quality of life and increases the societal healthcare burden.Early and accurate diagnosis of knee osteoarthritis is crucial for the treatment and prognosis of patients.Traditional diagnostic methods are not only subjective and time-consuming but also do not guarantee consistently high accuracy.OBJECTIVE:To develop an automatic diagnostic method for knee osteoarthritis based on deep learning,utilizing deep learning networks to improve diagnostic accuracy and efficiency.METHODS:A new network model,YOLOV8-ViT,was proposed by replacing the backbone network of YOLOv8n with the Efficient-ViT network and incorporating attention mechanisms for the automatic identification and classification of X-ray images of knee osteoarthritis.The experimental dataset included 5 078 X-ray images of patients with knee osteoarthritis obtained from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine.Three imaging physicians annotated the sites of knee osteoarthritis and classified them according to the Kellgren-Lawrence grading standard using Labelme software,and the results were combined.The evaluation indicators used in this study included Precision,F1 score,mean average precision(mAP),Recall,val/box_loss,val/cls_loss,and val/dfl_loss.RESULTS AND CONCLUSION:The experimental results showed that the YOLOV8-ViT model outperformed the YOLOv5n,YOLOv8n,and YOLOv9n models in terms of precision,mAP50,mAP50-95,F1 score,and Recall,while lowering val/box_loss,val/cls_loss,and val/dfl_loss by 0.496,0.45,and 0.523;1.037,0.305,and 0.728;and 0.267,0.654,and 0.854,respectively.These experimental data validate that this model has high detection accuracy.