Cancer immunotherapy is currently a very promising therapeutic strategy for treating tumors. However, its effectiveness is restricted by insufficient antigenicity and an immunosuppressive tumor microenvironment (ITME). Pyroptosis, a unique form of programmed cell death (PCD), causes cells to swell and rupture, releasing pro-inflammatory factors that can enhance immunogenicity and remodel the ITME. Nanomaterials, with their distinct advantages and different techniques, are increasingly popular, and nanomaterial-based delivery systems demonstrate significant potential to potentiate, enable, and augment pyroptosis. This review summarizes and discusses the emerging field of nanomaterials-induced pyroptosis, focusing on the mechanisms of nanomaterials-induced pyroptosis pathways and strategies to activate or enhance specific pyroptosis. Additionally, we provide perspectives on the development of this field, aiming to accelerate its further clinical transition.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To explore the effects of four extralevator abdominoperineal excision(ELAPE)procedures on the biomechanics of female pelvic floor through finite element analysis.Methods Six finite element models of the female pelvic floor were established,including a normal model,an ELAPE model,and four individual models.The maximum stress in each model was measured under the same pressure,and the stress distribution was observed.Results The maximum stress of non-levator ani muscle tissues on the partially reserved side and totally removed side of the levator ani muscle were 3.101±0.133 and 4.868±0.123 MPa in individual model 1,respectively,which were lower than the maximum stress in the ELAPE model(5.111±0.081 MPa;both P<0.01).The maximum stress in the non-levator ani muscle tissue were 5.138±0.091 MPa on both sides in individual model 2,which were not significantly different from that in the ELAPE model(P>0.05).The maximum stress of non-levator ani muscle tissues were 4.700±0.105 and 3.653±0.156 MPa in individual models 3 and 4,respectively,which were lower than the maximum stress in the ELAPE model(both P<0.01).Conclusion Three ELAPE procedures,including ELAPE with unilateral levator ani muscle resection plane close to the rectum,and the bilateral pubococcygeal muscle lateral resection of levator ani muscle and levator ani muscle in front of the rectum preserved could decrease stress in the non-levator ani muscle tissue on both sides.The effect is evident on the levator ani muscle partially reserved side of ELAPE with unilateral levator ani muscle resection plane close to the rectum.ELAPE with unilateral levator ani muscle resection plane close to the pelvic wall has no significant reduction effect on the non-levator ani muscle tissue on either side.ELAPE模型(均P<0.01).

Objective:To investigate whether the lung specific X protein(LUNX)gene can serve as a prognostic biomarker for non-small cell lung cancer related to immune cell infiltration.Methods:A total of 280 non-small cell lung cancer patients admitted to Hengshui People's Hospital from January 2020 to January 2023 were selected to detect the expression of LUNX gene in cancer tissue and adjacent tissues,and to analyze the relationship between LUNX gene and immune cell infiltration and prognosis survival status in the tumor microenvironment.Results:Compared with adjacent tissues,the expression level and positive rate of LUNX gene in non-small cell lung cancer tissue were increased,which were related to differentiation degree,lymph node metastasis and tumor staging(P<0.05).GEPIA database analysis showed that the LUNX gene was only slightly expressed or not expressed in other tissues,while its expression was elevated in LUAD and LUSC(P<0.05).The copy number of LUNX gene and LUNX gene were related to the level of immune cell infiltration(P<0.05).Survival analysis showed that high expression of the LUNX gene was associated with patient survival prognosis(P<0.05).Conclusion:The LUNX gene is specifically expressed in non-small cell lung cancer tissue,affecting the level of immune cell infiltration in non-small cell lung cancer,leading to an imbalance in the immune microenvironment,and is an important mechanism for causing patients prognostic death,which can be used as a prognostic biomarker for evaluating immune cell infiltration.

Atopic dermatitis (AD) is a common chronic inflammatory disease that often coexists with atopic diseases such as asthma, allergic rhinitis, and food allergies. In recent years, more and more studies have shown that AD is associated with various diseases such as cardiovascular diseases, autoimmune diseases, and mental disorders, which exacerbate the disease burden on patients with AD and severely affect their quality of life. This review summarizes AD-associated comorbidities reported in previous literature, analyzes their possible common pathogenesis, and explores potential treatments.

Objective:To analyze and compare the practical value of serum cystatin C(Scys C)and serum creatinine(SCr)in the assessment of kidney function in older adults.Methods:A retrospective, cross-sectional study was performed in 2 450 participants who were divided into a non-elderly group(<65 years)and an elderly group(≥65 years).Glomerular filtration rate(GFR), Scys C and SCr were measured by 99mTc-DTPA clearance, particle-enhanced immunoturbidimetry and an oxidase method, respectively.The χ2 test was used to compare increases in percentage of Scys C and SCr at the same GFR level.The screening value of Scys C and SCr for GFR<60 ml·min -1·1.73m -2was evaluated by the area under curve(AUC)of the receiver operating characteristic(ROC)curve.Values of 95% reference ranges were established for Scys C and SCr at different GFR levels. Results:The proportions of the general population with increased Scys C were 82.74%(556/672)and 94.74%(90/95), respectively, for GFR levels between 30~59 ml·min -1·1.73m -2and <30 ml·min -1·1.73m -2, while only 38.24%(257/672)and 75.79%(72/95)had elevated SCr levels( χ2=278.328, 13.571, both P<0.001).For the above GFR intervals, the proportions of older adults with increased Scys C were 84.81%(240/283)and 100.00%(43/43)respectively, and the proportions for non-elderly adults with increased Scys C were 81.23%(316/389)and 90.38%(47/52)( χ2=1.463, 4.364, P=0.226, 0.037), respectively.The screening value of Scys C for GFR<60 ml·min -1·1.73m -2was slightly better than SCr in terms of sensitivity, specificity and the Youden index.However, the sensitivity and specificity of Scys C in older adults were 76.4% and 75.7%, respectively, both lower than 78.7% and 84.0% in non-older adults.The variability of Scys C increased progressively with age.The reference range for Scys C was higher in older adults than in non-older adults at the same GFR level. Conclusions:When screening for GFR<60 ml·min -1·1.73m -2, the sensitivity and specificity of Scys C are slightly better than those of SCr, but are lower in older adults than in non-older adults.Scys C levels are higher and more variable in older adults.Using Scys C to assess GFR may lead to over-diagnosis of chronic kidney disease in older adults.

Objective:To investigate the effect of LRRK2G2019S mutation on activation of microglia after iron deprivation and its mechanism.Methods:(1) Microglia were differentiated from human induced pluripotent stem cells (IPSC) with the help of hematopoietic progenitor cells (HPC) and identified by immunofluorescent staining, and α-synuclein (α-syn) A53T mutant protein was obtained by protein purification technology. (2) Microglia were divided into control group, α-syn group, α-syn+ deferoxamine (DFO) group; phosphate buffer solution (PBS), 1 μmol/L purified α-syn A53T mutant protein, 1 μmol/L purified α-syn A53T mutant protein+30 mmol/L DFO were given respectively for 24 h. Fe 2+ concentration was detected by colorimetry, Rab35 protein expression was detected by Western blotting, intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and interleukin-6 ( IL-6), tumor necrosis factor-α ( TNF-α) and transforming growth factor-β ( TGF-β) mRNA expressions were detected by real time-PCR (RT-PCR); microglia culture supernatant (MCS) in the 3 groups were transfered to SH-SY5Y cells, and SH-SY5Y cell apoptosis was detected by flow cytometry. (3) Bidirectional DNA sequencing was used to detect leucine rich repeat kinase 2 ( LRRK2) gene mutations in microglia treated with 1 μmol/L purified α-syn A53T mutant protein. Microglia were divided into control group, α-syn group and α-syn+GSK3357679A group, and treated with corresponding drugs for 24 h, respectively (LRRK2 inhibitor GSK3357679A concentration: 10 nmol/L), and LRRK2 protein expression was detected by Western blotting; microglia were divided into control group, α-syn group, α-syn+GSK3357679A, and α-syn+GSK3357679A+DFO group, and treated with corresponding drugs for 24 h, Rab35 protein expression was detected by Western blotting, intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (4) Microglia were divided into control group, α-syn group, α-syn+rapamycin (RAPA) group, and treated with corresponding drugs for 24 h (concentration of autophagy inducer RAPA: 50 nmol/L); protein expressions of Rab35, P62 and microtubule-associated protein light chain 3 II (LC3II) were detected by Western blotting; intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (5) Microglia were divided into control group, α-syn group, and α-syn+Rab35 group, and treated with corresponding drugs for 24 h (concentration of Rab35 overexpressed plasmids: 1 μg/mL); Rab35, P62, and LC3II protein expressions were detected by Western blotting; ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. Results:(1) Immunofluorescent staining showed negative neuronal nuclei (NeuN) expression and positive ionized calcium-binding adapter molecule 1 (Iba1) expression in microglia, and high LRRK2 expression; PcDNA3.1-SNCA-A53T expression plasmid was constructed and α-syn A53T mutant protein was purified. (2) The Fe 2+ concentration in α-syn group was significantly higher than that in control group, and the Fe 2+ concentration in α-syn+DFO group was significantly lower than that in α-syn group ( P<0.05); the Rab35 protein and TGF-β mRNA expressions in control group, α-syn group and α-syn+DFO group were decreased successively, while the IL-6 and TNF-α mRNA expressions were increased successively, with significant differences ( P<0.05); ROS level and SH-SY5Y cell apoptosis rate in control group, α-syn group, α-syn+DFO group were increased successively. (3) Bidirectional DNA sequencing showed that the LRRK2G2019S mutation in microglia was the most obvious after α-syn A53T mutant protein stimulation; compared with the control group, the α-syn group had significantly increased LRRK2 protein expression, while the α-syn+GSK3357679A group had significantly decreased LRRK2 protein expression compared with α-syn group ( P<0.05); compared with the control group, the α-syn group had significantly decreased Rab35 protein and TGF-β mRNA expressions, and statistically increased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+GSK3357679A group had significantly increased Rab35 protein and TGF-β mRNA expressions, and statistically decreased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn+GSK3357679A group, α-syn+GSK3357679A+DFO group had significantly increased IL-6 and TNF-α mRNA expressions, and significantly decreased Rab35 protein and TGF-β mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group, the α-syn+GSK3357679A group had lower ROS level than the α-syn group, and the α-syn+GSK3357679A+DFO group had higher ROS level than the α-syn+GSK3357679A group. (4) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly increased P62 protein, IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+RAPA group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); the α-syn group had higher ROS level than the control group and α-syn+RAPA group. (5) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and statistically increased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); compared with the α-syn group, the α-syn+Rab35 group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group and α-syn+Rab35 group. Conclusion:LRRK2G2019S can induce neuroinflammation by inhibiting Rab35-related autophagy under iron deprivation, and Rab35 is expected to be a key factor in intervening neuroinflammation.

Objective:To elucidate the change of whole genome expression profile for the effect of melatonin on radiation-induced intestinal injury in mice.Methods:C57BL/6J male mice were administrated with melatonin at 10 mg/kg body weight by intraperitoneal injection once a day for five consecutive days before abdominal irradiation with 14 Gy of γ-rays. Small intestines were harvested 3 d after radiation. GO annotation and KEGG pathway of the differential genes involved in small intestine were explored by DNA microarray analysis.Results:Compared with the control group, 584 differential genes were up-regulated and 538 differential genes were down-regulated for administration group pre-irradiation. The overlapping differential genes were selected from the irradiated mice and the administrated mice pre-irradiation. There were 324 up-regulated genes and 246 down-regulated genes unique to the administrated mice pre-irradiation. GO annotation analysis of the differential genes indicated that the top 15 significantly enriched biological processes for the administrated mice pre-irradiation mainly included autophagosome assembly (GO: 0000045), autophagosome organization (GO: 1905037) and regulation of acute inflammatory response (GO: 0002673). The genes ATG12, ATG16L2 and AMBRA1 were involved in autophagosome assembly and autophagosome organization. The genes C3, CPN1, CD55, CFP, CNR1, C1QA, C2 and CREB3L3 were involved in the regulation of acute inflammation response. KEGG pathway analysis of the differential genes involved indicated that the top 15 significantly enriched pathways for the administrated mice pre-irradiation mainly included O-glycan biosynthesis (hsa00512), glycosphingolipid biosynthesis (hsa00603), ECM-receptor interaction (hsa04512) and biosynthesis of unsaturated fatty acids (hsa01040). qRT-PCR verification showed that the expressions of ATG12 and ATG16L2 genes involved in autophagy for the administrated mice pre-irradiation increased significantly compared with the irradiated mice ( t=2.40, 4.35, P<0.05). Conclusions:The differential genes related with the biological process of autophagy, acute inflammatory response and the pathway of unsaturated fatty acid biosynthesis might be involved in the effect of melatonin on radiation-induced intestinal injury.

Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Logistic Models ; Phenotype ; Risk Factors