Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Objective To investigate the neuroprotective effect of TGP on PS rats and determine the impact on the Ste20-like proline/alanine-rich kinase/Na+-K+-Cl cotransport(SPAK/NKCC1)signaling pathway.Methods After PS model was successfully established in 60 male SD rats(7 weeks old),they were randomly divided into model group,low-and high-dose TGP groups,high-dose TGP+negative control group,and high-dose TGP+WNK3 overexpression group,with 12 rats in each group.Another 12 healthy rats served as the control group.After modeling,50 or 200 mg/kg TGP was given to the rats of corresponding groups intragastrically,the overexpression plasmids of WNK3 were given to the rats from the high-dose TGP+WNK3 overexpression group through tail vein injection,and same volume of normal saline was given to the control group.All of these agents were administrated once per day for 7 consecutive days.ELISA was applied to de-tect serum levels of IL-6,IL-1β,MDA and SOD.HE staining was applied to detect the pathological morphology of the substantia nigra region in brain tissue.TUNEL staining was used to observe neuronal apoptosis.Immunohistochemistry was conducted to measure the expression of α-synucle-in(α-syn),and Western blotting for the expression of Bax,Bcl-2 and SPAK/NKCC1 signaling pathway related proteins(WNK3,p-SPAK,SPAK,p-NKCC1 and NKCC1).Results Compared with the model group,the pathological damage of neurons in substantia nigra was reduced in low-and high dose TGP groups,reduced contents of IL-6,IL-1β and MDA,lower neuronal apoptotic rate,and declined expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,but raised SOD content and Bcl-2 expression level(88.39±8.96 U/mg,119.57±12.01 U/mg vs 60.28±6.14 U/mg,P＜0.05;0.57±0.06,0.82±0.09 vs 0.38±0.04,P＜0.05).The intervention with WNK3 overexpression resulted in more severe pathological damage to neurons in the sub-stantia nigra,increased contents of IL-6,IL-1β and MDA,higher neuronal apoptotic rate,enhanced expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,and reduced SOD con-tent and Bcl-2 expression level when compared with the high-dose TGP+negative control group(P＜0.05).Conclusion TGP exerts neuroprotective effects on PS rats,and its mechanism is re-lated to the inhibition of the SPAK/NKCC1 signaling pathway.

Medical imaging technology plays a crucial role in clinical diagnosis and treatment. Image compression technology provides robust technical support for the storage and transmission of massive medical imaging data, serving as an effective safeguard for hospital data backup and telemedicine. The technology holds broad application prospects in the medical field, enabling the processing of various imaging modalities, multidimensional imaging, and medical video imaging. This study elaborates on general image and video compression algorithms, the application of compression algorithms in the medical field, and the performance metrics of medical image compression, thereby providing critical technical support for enhancing clinical diagnostic efficiency and data management security.

OBJECTIVE: To observe the effects of Xingnao Kaiqiao acupuncture technique (for regaining consciousness and opening orifice) on methylation of N6-methyladenosine (m6A), and key methyltransferases and demethylases, so as to clarify the mechanism of acupuncture on cerebral ischemia-reperfusion injury (CIRI). METHODS: Of 68 male Sprague-Dawley rats of SPF grade, 15 rats were randomly selected as a sham-operation group, and the remaining rats were subjected to the model of middle cerebral artery occlusion using the suture ligation. CIRI was induced by ischemia for 2 h followed by reperfusion. Rats that failed to modeling or died were excluded. The rest 45 rats were randomly divided into three groups, i.e. model group, acupuncture group, and non-point acupuncture group, with 15 rats in each group. The rats in the acupuncture group were treated with acupuncture at bilateral "Neiguan" (PC6) and "Shuigou" (GV26). In the non-point acupuncture group, acupuncture was delivered at three non-points, located 3 mm below the bilateral midaxillary line and 3 mm lateral to the tip of the coccyx. One intervention was operated in these two acupuncture groups and the needles were retained for 30 min. Before modeling start and 2 h after ischemia, a laser speckle flowmeter was used to monitor the cerebral blood perfusion. In 2 h of ischemia and 24 h of reperfusion, the neurological behavioral score was evaluated. The volume of rat cerebral infarction was determined by triphenyltetrazolium chloride (TTC) staining, and the level of m6A methylation in ischemic cortical area was detected by Dot blot, and the protein and mRNA expression of the demethylase i.e. fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and key methyltransferases, i.e. methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms' tumor 1-associated protein (WTAP) in ischemic cortical area were detected by Western blot and real-time PCR. RESULTS: Cerebral blood perfusion decreased by>70% after 2 h ischemia. Compared with the sham-operation group, the neurobehavioral score and the percentage of cerebral infarction volume increased in the model group (P<0.01); the level of m6A methylation in the ischemic cortical area increased (P<0.01), the protein and mRNA expression of FTO decreased (P<0.01), and that of ALKBH5, METTL3, and METTL14 increased (P<0.01, P<0.05) in the model group. When compared with the model group and the non-point acupuncture group, the acupuncture group showed a decrease in the neurobehavioral score and the percentage of cerebral infarction volume (P<0.01), the level of m6A methylation in the ischemic cortical area was reduced (P<0.01, P<0.05), and the protein and mRNA expression of FTO was elevated (P<0.01). CONCLUSION Xingnao Kaiqiao acupuncture technique presents its protective effect on the brain in the rats with CIRI, which is related to up-regulating the expression of FTO and modulating m6A methylation.
Animals ; Rats, Sprague-Dawley ; Male ; Acupuncture Therapy ; Reperfusion Injury/genetics* ; Rats ; Brain Ischemia/genetics* ; Humans ; Adenosine/metabolism* ; Methylation ; Acupuncture Points ; Cerebral Cortex/metabolism*

Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]₄P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism* ; Adenosine Triphosphatases/metabolism* ; Ophiopogon/drug effects* ; Soil Pollutants/toxicity* ; Plant Proteins/metabolism* ; Stress, Physiological ; Multigene Family ; Gene Expression Regulation, Plant

Yes-associated protein (YAP), the key transcriptional co-factor and downstream effector of the Hippo pathway, has emerged as one of the primary regulators of neural as well as glial cells. It has been detected in various glial cell types, including Schwann cells and olfactory ensheathing cells in the peripheral nervous system, as well as radial glial cells, ependymal cells, Bergmann glia, retinal Müller cells, astrocytes, oligodendrocytes, and microglia in the central nervous system. With the development of neuroscience, understanding the functions of YAP in the physiological or pathological processes of glia is advancing. In this review, we aim to summarize the roles and underlying mechanisms of YAP in glia and glia-related neurological diseases in an integrated perspective.
Humans ; Animals ; Neuroglia/metabolism* ; Signal Transduction/physiology* ; YAP-Signaling Proteins ; Nerve Regeneration/physiology* ; Nervous System Diseases/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism*

Objective:To explore a modeling method for establishing a performance accounting system under the requirements of high-quality development,with the goal of helping public hospitals return to public welfare and improving the quality and efficiency of their operation.Methods:On the basis of comprehensive analysis of the advantages and disadvantages of various performance accounting tools,it is proposed to conduct the evaluation based on the order of the technical labour value chain,that is,to establish Basic Value Evaluation madule,Balanced Score Card(BSC)Evaluation and Key Quality Index(KPI)madule Evaluation,and the modules are combined through the multiplication principle.Results:Under the guidance of this modeling method,a set of performance accounting system has been established which not only emphasizes the"dual-core"operation of public welfare and operational quality and efficiency,but also adapts to the demand of public hospitals of different scales and at different stages of development.Conclusion:Effective accounting system modeling methods can be oriented to build a performance accounting system that combines public welfare and operational quality and efficiency,with high adaptability,operability,and value of popularization and application.

Objective To investigate the protective effect and mechanism of tanshinone ⅡA on D-galactosamine(D-GalN)-induced acute liver failure in rats.Methods SD rats were randomly di-vided into control group,model group(intraperitoneal injection of 1.1 g/kg D-GalN),low-dose group(intraperitoneal injection of 1.1 g/kg D-GalN+daily gavage of 25 mg/kg tanshinone ⅡA),and High-dose group(intraperitoneal injection of 1.1 g/kg D-GalN+daily gavage of 50 mg/kg tan-shinone ⅡA).Liver function indicators[aspartate aminotransferase(AST),alanine aminotransferase(ALT),and γ-glutamyltransferase(γ-GT)]were measured using a Hitachi7600-210 biochemical an-alyzer,and serum total bilirubin(TBIL)and direct bilirubin(DBIL)levels were determined.The mitotic index(MI)and proliferating cell nuclear antigen(PCNA)positivity in liver tissues were examined.Enzyme-linked immunosorbent assay(ELISA)was used to detect plasma levels of tumor necrosis factor(TNF-α),interleukin(IL)-1β,IL-10,and IL-6 in rats from each group.Kits were employed to measure superoxide dismutase(SOD),glutathione(GSH),and malondialdehyde(MDA)contents in liver tissues of rats from each group.The TUNEL method was adopted to detect hepatocyte apoptosis rates in liver tissues,and immunoblotting was used to assess the expression of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2)and extracellular signal-regu-lated kinase 1/2(ERK1/2)proteins in liver tissues.Results Compared with the control group,the model group exhibited increased p-ERK1/2 protein expression(P＜0.05).Compared with the model group,both the low-dose and high-dose groups showed decreased p-ERK1/2 protein expres-sion(P＜0.05).The model group had an increased hepatocyte apoptosis index compared with the control group(P＜0.05).Both the low-dose and high-dose groups demonstrated decreased hepato-cyte apoptosis indices compared with the model group(P＜0.05).Compared with the control group,the model group had increased MDA levels and decreased SOD and GSH levels(P＜0.05).Both the low-dose and high-dose groups exhibited decreased MDA levels and increased SOD and GSH levels compared with the model group(P＜0.05).The model group showed increased levels of TNF-α,IL-1β,IL-10,and IL-6 compared with the control group(P＜0.05).Both the low-dose and high-dose groups had decreased levels of TNF-α,IL-1 β,IL-10,and IL-6 compared with the model group(P＜0.05).Compared with the control group,the model group had decreased MI and PCNA positivity rates(P＜0.05).Both the low-dose and high-dose groups exhibited increased MI and PCNA positivity rates compared with the model group(P＜0.05).The model group had in-creased AST,ALT,γ-GT,TBIL and DBIL values compared with the control group(P＜0.05).Both the low-dose and high-dose groups showed decreased AST,ALT,γ-GT,TBIL and DBIL val-ues compared with the model group(P＜0.05).Conclusion Tanshinone ⅡA may alleviate D-GalN-induced acute liver failure in rats through the ERK1/2 signaling pathway.