Objective : To explore the role of lysophosphatidylcholine acyltransferase 3(LPCAT3) in Erastin-induced ferroptosis of acute myeloid leukemia(AML) cells and its related molecular regulatory mechanisms. Methods : Tetrazolium salt(MTS) method was used to detect the sensitivity of different AML cells to the classic ferroptosis inducer Erastin, real time quantitative polymerase chain reaction(qPCR) was used to detect the basal expression level ofLPCAT3mRNA, and the correlation between them was analyzed. Lentivirus-mediatedLPCAT3overexpression AML cell lines(OE group) and negative control lines(NC group) were constructed. After Erastin intervention, MTS, flow cytometry, and micromethods were used to detect cell viability, lipid reactive oxygen species(ROS), and Malondialdehyde(MDA), respectively. qPCR and Western blot were used to detect unfolded protein response(UPR) classic pathway signaling molecules(PERK, ATF4, GRP78, etc.) expression levels. The above ferroptosis-related indicators were detected after combined intervention with the UPR inhibitor 4-phenylbutyric acid(4-PBA), and the regulatory relationship was analyzed. Results : Four different types of AML cells had different sensitivities to ferroptosis, among which K562 cells were relatively insensitive. The IC50of the four types of AML cells to Erastin was negatively correlated with the expression level ofLPCAT3(r=-0.919,P<0.001). After Erastin intervention, the cell viability of K562 cells in the OE group was significantly inhibited by Erastin compared with the NC group(P<0.001), and the levels of lipid ROS and MDA increased(P<0.001). The results of qPCR and Western blot showed that, compared with the NC group, the mRNA and protein expression of UPR classic pathway moleculesPERK,ATF4, andGRP78mRNA and protein increased in the OE group(P<0.01). After inhibiting the UPR pathway by 4-PBA, the viability of K562 cells decreased(P<0.01), and lipid ROS and MDA levels increased(P<0.01) compared with the uninhibited state. Conclusion Overexpression ofLPCAT3can promote ferroptosis in K562 cells, and this process is negatively regulated by the classical UPR pathway PERK/ATF.

Objective: To investigate trends in incidence and mortality of colorectal cancer in Nantong City, Jiangsu Province from 2013 to 2022. Methods: Data on incidence and mortality of colorectal cancer from 2013 to 2022 in Nantong City were collected through the Nantong City cancer registry. The crude incidence, crude mortality, average age at onset, and average age at death of colorectal cancer were calculated. Chinese population-standardized incidence, Chinese population-standardized mortality, Chinese population-standardized average age at onset and Chinese population-standardized average age at death were calculated using the age structure of the standard population from the Fifth National Population Census in 2000. Trends in incidence and mortality of lung cancer from 2013 to 2022 were evaluated using average annual percent change (AAPC). Trends in the Chinese population-standardized average age at onset and Chinese population-standardized average age at death of lung cancer from 2013 to 2022 were evaluated using the linear regression model. Results: From 2013 to 2022, the crude incidence and Chinese population-standardized incidence of colorectal cancer in Nantong City increased from 33.63/105 and 16.05/105 to 53.82/105 and 19.62/105, respectively, showing upward trends (AAPC=5.665% and 2.467%, both P<0.05). The crude mortality increased from 15.99/105 in 2013 to 25.65/105 in 2022, also showing an upward trend (AAPC=5.514%, P<0.05), while no statistically significant trend was found in the Chinese population-standardized mortality (P>0.05). The Chinese population-standardized incidence of colorectal cancer showed upward trends in both males and females (AAPC=2.666% and 1.790%, both P<0.05). The Chinese population-standardized mortality showed an upward trend in males (AAPC=1.966%, P<0.05), but no statistically significant trend was found in females (P>0.05). The crude incidence of colorectal cancer in the groups aged 40-<50 years, 50-<60 years, 60-<70 years, 70-<80 years, and ≥80 years showed upward trends (AAPC=4.045%, 2.833%, 2.300%, 1.948%, and 1.775%, all P<0.05), and the crude mortality in the group aged ≥80 years showed an upward trend (AAPC=3.240%, P<0.05). The average age at onset of colorectal cancer increased at an annual average of 0.156 years (P<0.05), while the trend in the Chinese population-standardized average age at onset was not statistically significant (P>0.05). The average age at death and the Chinese population-standardized average age at death increased at an annual average of 0.325 and 0.153 years, respectively (both P<0.05). Conclusions From 2013 to 2022, both the crude incidence and mortality of colorectal cancer in Nantong City showed upward trends. Males and individuals aged ≥40 years faced a higher risk of both incidence and mortality. It is recommended to implement comprehensive prevention and control measures targeting these high-risk populations to reduce the burden of colorectal cancer.

Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Sugarcane (Saccharum spp.) is an important sugar crop. Biotic and abiotic stresses such as diseases, cold, and drought are major factors limiting sugarcane production. β-1,3-glucanase (EC 3.2.1.39), a member of the pathogenesis-related protein family, plays an essential role not only in the plant defenses against pathogens but also in plant growth, development, and abiotic stress responses. To systematically investigate the sugarcane β-1,3-glucanase gene family, 132 glycoside hydrolase (GH) 17 family members were identified in the genomes of the sugarcane wild species Saccharum spontaneum 'Np-X', the tropical species S. officinarum 'LA-Purple', and the Saccharum spp. hybrid cultivar 'R570'. The results of the phylogenetic analysis categorized them into four subfamilies, of which subfamily Ⅳ had the largest proportion of members (102). The members of the sugarcane GH17 gene family contained five conserved motifs and 0-16 introns. The majority of the GH17 genes exhibited a genome-wide replication pattern, with 89.50% originating from S. spontaneum 'Np-X' and S. officinarum 'LA-Purple', while 58.10% of them in the Saccharum spp. hybrid cultivar 'R570' belonged to the discrete replication type. Four major classes of cis-acting elements were identified in the promoters, including the elements related to plant growth, development, and tissue-specific expression (14.21%), light-responsive elements (38.24%), biotic or abiotic stress-responsive elements (9.18%), and hormone-responsive elements (38.37%), which suggested that this gene family was involved in plant growth, development, hormone responses, and stress responses. Transcriptome and quantitative real-time PCR (RT-qPCR) analyses showed that the sugarcane GH17 genes exhibited tissue-specific expression and were differentially expressed under low temperature, drought, and hormone treatments, as well as during the interactions between different sugarcane genotypes and Sporisorium scitamineum, suggesting their potential roles in plant defenses. In addition, some SsGlu genes (SsGlu5, SsGlu20, SsGlu21, SsGlu25, SsGlu28, and SsGlu39) were expected to serve as candidate stress-related genes. This study lays a foundation for further revealing the molecular mechanisms of the stress resistance of sugarcane via β-1,3-glucanase genes.
Saccharum/physiology* ; Stress, Physiological/genetics* ; Glucan 1,3-beta-Glucosidase/metabolism* ; Multigene Family ; Phylogeny ; Gene Expression Regulation, Plant ; Plant Proteins/genetics*

Objective:To compare the efficacy of various machine learning models in predicting renal function decline after robot-assisted partial nephrectomy(RAPN),and to provide evidence for clinical risk stratification.Methods:This study retrospectively in-cluded the clinical data of 733 patients with renal cell carcinoma undergoing RAPN at the Urology Department of The First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023.Demographic characteristics,laboratory indicators,and perioperative parameters were integrated to construct seven machine learning models.Key predictors were interpreted using Shap-ley additive explanations(SHAP).Model performance was evaluated using the area under the receiver operating characteristic curve(AUC).Results:The random forest model demonstrated the best predictive performance(AUC=0.84).SHAP analysis identified neutrophil-to-lymphocyte ratio,tumor diameter,the international normalized ratio of prothrombin time,white blood cell count,and in-traoperative blood loss as significant factors influencing postoperative renal function decline.Conclusion:This study provides a poten-tial predictive tool for clinical practice,aiding in identifying high-risk patients and optimizing postoperative management strategies.

Objective To determine the optimal extraction process for kaempferol from Alpinia officinarum Hance and to investigate its antioxidant activity.Methods Based on single-factor experimental data,this study employed the Box-Behnken central composite design and response surface methodology(RSM),combined with high-performance liquid chromatography(HPLC),to plot response surface and contour maps using kaempferol content as the response value.The optimal parameters for ethanol concentration,solid-liquid ratio,extraction time,and extraction temperature were selected.The antioxidant activity of kaempferol was comprehensively evaluated by calculating the radical scavenging rate using the DPPH radical scavenging assays.Results The optimal extraction conditions were determined to be an ethanol concentration of 84%,a solid-liquid ratio of 1∶80,an extraction time of 2 hours,and an extraction temperature of 82℃.Under these conditions,the kaempferol content extracted from Alpinia officinarum Hance reached 0.034 16%.In the DPPH radical scavenging assay,the extract showed a scavenging rate of 91.20%at a concentration of 1 mg/mL.Conclusion The optimized extraction process for kaempferol from Alpinia officinarum Hance was obtained using the Box-Behnken response surface design method,and this process is practical and feasible.The DPPH radical scavenging assay demonstrated that kaempferol from Alpinia officinarum Hance possesses antioxidant activity.

Bacteriophages possess the ability to infect and kill bacteria and have now been applied in various oral diseases,providing new insights for the prevention and treatment of oral diseases.They are expected to become a novel biological antibacterial agent for treating oral diseases.This paper comprehensively discusses the application of bacteriophages in oral medicine from six aspects:the concept and application prospects of bacteriophages,four common infectious diseases of the oral cavity and their pathogenic bacteria,existing treatment methods,and the application and outlook of bacteriophages in these diseases.Lay a theoretical basis for the clinical implementation of phage therapy.

ObjectiveTo explore the recognition of oral breath odor map of chronic atrophic gastritis （CAG） patients with dampness-heat syndrome by electronic nose technique. MethodsPatients with chronic gastritis were recruited， including 60 cases in CAG group of dampness-heat syndrome， 50 cases in CAG group of non-dampness-heat syndrome， 60 cases in chronic non-atrophic gastritis （CNAG） group of dampness-heat syndrome， 50 cases in CNAG group of non-dampness-heat syndrome， and 30 cases of healthy volunteers were selected to set up the health control group. Ten cases in the CAG dampness-heat group and 50 cases in the CAG non-dampness-heat group were selected to form the CAG group， and 10 cases in CNAG dampness-heat group and 50 cases in CNAG non-dampness-heat group were selected to form the CNAG group. In addition to the health control group， the remaining patients were tested for Helicobacter pylori （Hp）； the electronic nose （GISXM-MQWA01） was used to collect the oral breath odor of all the participants to draw the mapping， and amplitudes and slopes of each curve （including curves A， B， C， D， E， F， G， H， I， J） of the oral odor mapping of health control group， CAG group， CNAG group， CAG dampness-heat group， CAG non-dampness-heat group， and CNAG dampness-heat group was compared. The modified transformer model was used to classify the odor mapping characteristics， and the confusion matrix method was used to evaluate the classification model， with metrics including accuracy and area under ROC curve （AUC）. ResultsThe Hp positivity rate in CAG dampness-heat group was 80.00% （48/60）， CAG non-dampness-heat group was 62.00% （31/50）， CNAG dampness-heat group was 46.67% （28/60）， and CNAG non-dampness-heat group was 42.00% （21/50）； the difference in Hp positivity rate between CAG dampness-heat group and CAG non-dampness-heat group was statistically significant （P＜0.05）. The amplitudes of response curves A， B， C， D， F， G， and I， and slopes of A and F in the odor mapping of the CAG group were lower than those in health control group， while the amplitude and slope of curve E were higher than those in the health control group and CNAG group （P＜0.05 or P＜0.01）； The amplitude of the response curves A， B， C， D， F， G， and I， and slopes of A， D， and F in the CNAG group were lower than those in the health control group （P＜0.05 or P＜0.01）. The amplitude of response curve D and slope of response curve J in the odor mapping of the CAG dampness-heat group were higher than those in CNAG dampness-heat group， the amplitude of curve F was lower than that in CAG non-dampness-heat group， and the amplitude of curve H and slopes of curve A， H， and J were higher than those in CAG non-dampness-heat group （P＜0.05）. The recognition accuracy of CAG group and health control group reached 77.78%， AUC = 0.88； the recognition accuracy of CAG group and CNAG group was 69.44%， AUC = 0.61； the recognition accuracy of CAG dampness-heat group and CAG non-dampness-heat group reached 75.8%， AUC=0.70. ConclusionElectronic nose technology can make a more accurate identification of the oral breath odor in CAG patients with dampness-heat syndrome， with a decrease in the amplitude of the curve F and an increase in the amplitude of the curve H and in the slopes of the curves A， H， and J may as the characteristics of their odor mapping.