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 The clinical distribution characteristics and drug resistance of carbapenem-resistant Pseudomonas aeruginosa(CRPA)were analyzed to provide reference for clinical anti-infection treatment.Methods The data of hospitalized patients with Pseudomonas aeruginosa(PA)cultured and isolated from Enze Hospital,Taizhou Enze Medical Center(Group)from January 2018 to December 2022 were retrospectively analyzed,and the clinical departments,specimen types,patient ages and sensitivity to commonly used antibiotics for CRPA strains were statistically analyzed.Results A total of 1660 strains of PA were collected,of which 314 strains(18.92%)were CRPA.The detection rate of CRPA strains was the highest in 2018.The detection departments were mainly intensive medicine,respiratory and critical care medicine.The specimen types were mainly sputum.The age of patients was mainly between 61-80 years old.According to the drug sensitivity,there were small fluctuations in the resistance rates of CRPA strains to common antibacterial drugs.The resistance rate of piperacillin was lower than 40%,while the resistance rate of ticarcillin/clavulanate was consistently higher than 50%.The resistance rates of aminoglycosides and piperacillin/tazobactam were lower than 15%.Conclusion From 2018 to 2022,the detection rate of CRPA strains decreased first and then increased.The resistance rate of piperacillin/tazobactam was lower than 15%in past 5 years,so it can be preferred for clinical empirical treatment.

Objective By analyzing the clinical characteristics and related factors of treatment outcomes in patients with nontuberculous mycobacterial pulmonary disease(NTM-PD)in Taizhou,this study provided reference for the management,diagnosis and treatment of NTM-PD.Methods Clinical characteristics of 167 patients with NTM-PD isolated in Taizhou Hospital of Zhejiang Province from January 2016 to December 2021 were retrospectively analyzed.The differences in clinical characteristics were compared between cured group and failed group of 83 cases with Mycobacterium avium complex pulmonary disease(MAC-PD).Results MAC-PD was the most common species among the 167 cases of NTM-PD,accounting for 94.6％,88 patients were treated.The cure rate was 47.7％.Compared with cured group,the patients in failed group had statistical differences in body mass index(BMI)≤ 18.5kg/m2,acid-fast bacilli smear-positive,combined with previous pulmonary tuberculosis,imaging with fibrous-cavernous type and unstandardized medication(P＜0.05).Conclusion MAC-PD is the most common among NTM-PD patients in Taizhou.BMI ≤ 18.5kg/m2,acid-fast bacilli smear-positive,combined with previous pulmonary tuberculosis,imaging with fibrous-cavernous type and unstandardized medication of MAC-PD were more difficult to treat.

Pulmonary infection by pathogenic microorganisms is a common disease of the respiratory system with high mortality and poor prognosis,but its pathogenesis remains unclear.In recent years,single-cell RNA sequencing(scRNA-seq)has been widely used in the study of lung infection to provide an atlas of immune cells of patients,identify new immune cell subsets,analyze differential expression genes,reveal pathways related to inflammatory immune pathways in pathogenic microbial infection,monitor the levels of cytokines,and identify novel biomarkers of lung infection.There-fore,this paper presents a review of the application of scRNA-seq in pulmonary infection by pathogenic microorganisms.

AIM:This study aims to investigate the effects and mechanisms of silent information regulator 6(SIRT6)on carbon tetrachloride(CCl4)-induced liver fibrosis in mice,as well as the expression changes in the down-stream pathways of hepatic stellate cells after SIRT6 silencing.METHODS:Thirty male C57BL/6J mice were randomly divided into a normal control group(n=6)and a model group(modeling at 2,4,8,12 weeks,n=24).A liver fibrosis model in mice was prepared by intraperitoneal injection of CCl4 twice a week for 12 weeks.Serum alanine aminotransfer-ase(ALT)and aspartate aminotransferase(AST)levels were measured to assess liver injury.Hematoxylin-eosin(HE)and Masson staining were used to observe the pathological changes in mouse liver tissues.Immunohistochemical staining was conducted to detect the expression of α-smooth muscle actin(α-SMA)in the liver,Western blot analysis was used to measure the expression of liver α-SMA,SIRT6,acetyl histone H3 at Lys9(H3K9ac),acetyl histone H3 at Lys56(H3K56ac),interleukin-1β(IL-1β),and IL-18 proteins.Hepatic stellate cells-T6(HSC-T6)underwent SIRT6 gene si-lencing,divided into NC siRNA group and SIRT6 siRNA group,with Western blot performed to detect the expression of SIRT6,H3K9ac,and H3K56ac proteins.RESULTS:Compared with the normal control group,the serum ALT and AST levels in the model group were significantly increased(P<0.05);HE and Masson staining results showed that the patho-logical changes in the liver of the model group worsened over time,with an increase in collagen fiber deposition.Both im-munohistochemistry and Western blot showed that the expression of liver α-SMA significantly increased at 8 and 12 weeks in the model group(P<0.05).Western blot results showed that the expression of SIRT6 protein in the liver of all model group mice was lower than that in the normal control group(P<0.05),and decreased gradually with the progression of liv-er fibrosis;also,the expression levels of H3K9ac,H3K56ac,IL-1β,and IL-18 in the liver of the model group mice were significantly elevated at 8 and 12 weeks(P<0.05);after SIRT6 silencing,compared with the NC siRNA group,the levels of H3K9ac and H3K56ac in the SIRT6 siRNA group significantly increased(P<0.05).CONCLUSION:The deficiency of SIRT6,by abnormally increasing H3K9ac and H3K56ac,raises the expression of IL-1β and IL-18,intensifying the in-flammatory response and promoting the progression of liver fibrosis,indicating that the aberrant expression of SIRT6 is in-volved in the development of liver fibrosis.