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This comprehensive review explores the intricate mechanisms of PANoptosis and its implications in cancer. PANoptosis, a convergence of apoptosis, pyroptosis, and necroptosis, plays a crucial role in cell death and immune response regulation. The study delves into the molecular pathways of each cell death mechanism and their crosstalk within PANoptosis, emphasizing the shared components like caspases and the PANoptosome complex. It highlights the significant role of PANoptosis in various cancers, including respiratory, digestive, genitourinary, gliomas, and breast cancers, showing its impact on tumorigenesis and patient survival rates. We further discuss the interwoven relationship between PANoptosis and the tumor microenvironment (TME), illustrating how PANoptosis influences immune cell behavior and tumor progression. It underscores the dynamic interplay between tumors and their microenvironments, focusing on the roles of different immune cells and their interactions with cancer cells. Moreover, the review presents new breakthroughs in cancer therapy, emphasizing the potential of targeting PANoptosis to enhance anti-tumor immunity. It outlines various strategies to manipulate PANoptosis pathways for therapeutic purposes, such as targeting key signaling molecules like caspases, NLRP3, RIPK1, and RIPK3. The potential of novel treatments like immunogenic PANoptosis-initiated therapies and nanoparticle-based strategies is also explored.

With the continuous increase in the number of electric vehicles (EVs) and the rapid development of demand response (DR) technology, the power grid faces unprecedented challenges. A two-stage dual-level dispatch optimization model of multiple virtual power plants based on a Stackelberg game is proposed in this paper. In the day-ahead stage, a two-layer optimization scheduling model is established, where the EV layer optimizes its actions for maximum comprehensive user satisfaction, while the VPP layer optimizes its actions for minimal operating costs and interaction power, determining the scheduling arrangements for each distributed energy resource. In the intraday stage, a Stackelberg game model is constructed with the distribution network operator (DNO) as the leader, aiming to maximize profits, and the VPP as the follower, aiming to minimize its own operational costs, with both parties engaging in a game based on electricity prices and energy consumption strategies. In the simulation case study, the effectiveness of the constructed model was verified. The results show that the model can effectively reduce user costs, thereby increasing the comprehensive satisfaction of EV users by 20.7% and reducing VPP operating costs by 13.37%.

Hyperbilirubinemia is a common cause of hospital readmission among neonates, but the factors contributing to post-discharge readmission remain unclear. Our study aimed to identify predictive factors associated with readmission for neonatal hyperbilirubinemia. This retrospective case-control study included 421 neonates born at ≥ 35 weeks of gestation with hyperbilirubinemia between January and December 2021. The neonates were divided into a readmission group and a control group, and logistic regression was used to identify predictive factors associated with readmission. Among the 421 neonates studied, 32 (7.6%) were readmitted. Logistic regression analysis identified preterm birth (<37 weeks), ABO hemolysis, Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, and Total Serum Bilirubin (TSB) level at discharge as significant predictive factors for readmission due to hyperbilirubinemia in newborns. Additionally, a decrease in birth weight was significantly linked to an increased risk of readmission (OR = 0.998, P = 0.013), although the effect size was relatively small. Prolonging hospitalization and implementing robust post-discharge monitoring may be essential for neonates with prematurity, ABO hemolysis, G6PD deficiency, or elevated TSB levels at discharge.

Amplification and sequencing of 16S amplicons are widely used for profiling the structure of oral microbiota. However, it remains not clear whether and to what degree DNA extraction and targeted 16S rRNA hypervariable regions influence the analysis. Based on a mock community consisting of five oral bacterial species in equal abundance, we compared the 16S amplicon sequencing results on the Illumina MiSeq platform from six frequently employed DNA extraction procedures and three pairs of widely used 16S rRNA hypervariable primers targeting different 16S rRNA regions. Technical reproducibility of selected 16S regions was also assessed. DNA extraction method exerted considerable influence on the observed bacterial diversity while hypervariable regions had a relatively minor effect. Protocols with beads added to the enzyme-mediated DNA extraction reaction produced more accurate bacterial community structure than those without either beads or enzymes. Hypervariable regions targeting V3-V4 and V4-V5 seemed to produce more reproducible results than V1-V3. Neither sequencing batch nor change of operator affected the reproducibility of bacterial diversity profiles. Therefore, DNA extraction strategy and 16S rDNA hypervariable regions both influenced the results of oral microbiota biodiversity profiling, thus should be carefully considered in study design and data interpretation.

Chemotherapy resistance observed in patients with colorectal cancer (CRC) may be related to the presence of cancer stem cells (CSCs), but the underlying mechanism(s) remain unclear. Carcinoma-associated fibroblasts (CAFs) are intimately involved in tumor recurrence, and targeting them increases chemo-sensitivity. We investigated whether fibroblasts might increase CSCs thus mediating chemotherapy resistance. CSCs were isolated from either patient-derived xenografts or CRC cell lines based on expression of CD133. First, CSCs were found to be inherently resistant to cell death induced by chemotherapy. In addition, fibroblast-derived conditioned medium (CM) promoted percentage, clonogenicity and tumor growth of CSCs (i.e., CD133+ and TOP-GFP+) upon treatment with 5-fluorouracil (5-Fu) or oxaliplatin (OXA). Further investigations exhibited that exosomes, isolated from CM, similarly took the above effects. Inhibition of exosome secretion decreased the percentage, clonogenicity and tumor growth of CSCs. Altogether, our findings suggest that, besides targeting CSCs, new therapeutic strategies blocking CAFs secretion even before chemotherapy shall be developed to gain better clinical benefits in advanced CRCs.

Background Focal adhesion plays an essential role in tumour invasiveness and metastasis. Hippo component YAP has been widely reported to be involved in many aspects of tumour biology. However, its role in focal adhesion regulation in breast cancer remains unexplored. Methods Tissue microarray was used to evaluate YAP expression in clinical breast cancer specimens by immunohistochemical staining. Cell migration and invasion abilities were measured by Transwell assay. A cell adhesion assay was used to measure the ability of cell adhesion to gelatin. The focal adhesion was visualized through immunofluorescence. Phosphorylated FAK and other proteins were detected by Western blot analysis. Gene expression profiling was used to screen differently expressed genes, and gene ontology enrichment was performed using DAVID software. The gene mRNA levels were measured by quantitative real-time PCR. The activity of the THBS1-promoter was evaluated by dual luciferase assay. Chromatin immunoprecipitation (ChIP) was used to verify whether YAP could bind to the THBS1-promoter region. The prediction of potential protein-interaction was performed with the String program. The ChIP sequence data of TEAD was obtained from the ENCODE database and analysed via the ChIP-seek tool. The gene expression dataset (GSE30480) of purified tumour cells from primary breast tumour tissues and metastatic lymph nodes was used in the gene set enrichment analysis. Prognostic analysis of the TCGA dataset was performed by the SurvExpress program. Gene expression correlation of the TCGA dataset was analysed via R2: Genomics Analysis and Visualization Platform. Results Our study provides evidence that YAP acts as a promoter of focal adhesion and tumour invasiveness via regulating FAK phosphorylation in breast cancer. Further experiments reveal that YAP could induce FAK phosphorylation through a TEAD-dependent manner. Using gene expression profiling and bioinformatics analysis, we identify the FAK upstream gene, thrombospondin 1, as a direct transcriptional target of YAP-TEAD. Silencing THBS1 could reverse the YAP-induced FAK activation and focal adhesion. Conclusion Our results unveil a new signal axis, YAP/THBS1/FAK, in the modulation of cell adhesion and invasiveness, and provides new insights into the crosstalk between Hippo signalling and focal adhesion.

SII and SIRI are two novel systemic inflammation indexes that were suggested in predicting poor outcomes in cancers. However, no studies have examined their effect on cardiovascular diseases (CVDs) and all-cause mortality. Thus, this study aims to investigate associations between SII, SIRI, and the risks for CVDs and all-cause mortality. A total of 85,154 participants from the Kailuan cohort were included and followed up for incidents of CVDs (including MI, stroke) and all-cause death for 10 years. Multiple Cox regression was used to calculate the adjusted hazard ratios (HRs). During the follow-up period, 4262 stroke events, 1233 MI events, and 7225 all-cause deaths were identified, respectively. Compared with the lowest quantile (Q1) of SII or SIRI, after adjusted for most cardiovascular risk factors, both indexes showed positive associations with the risk for stroke (adjusted HRs in Q4 were 1.264 (95% CI: 1.157,1.382) for SII, 1.194 (95% CI: 1.087,1.313) for SIRI), and all-cause death (adjusted HRs in Q4 were 1.246 (95% CI: 1.165,1.331) for SII, 1.393 (95% CI: 1.296,1.498) for SIRI). Additionally, higher SII and SIRI are also associated with increased risk of hemorrhagic stroke and ischemic stroke. Higher SIRI but not SII exhibited a higher MI risk, the adjusted HR in Q4 was 1.204 (1.013,1.431). The significant association remained after additional adjustment for CRP. Subgroup analysis and sensitivity analysis displayed consistent results except for SIRI with MI, where the association did not arrive at significance in subjects aged ≥60. Elevated SII and SIRI increased the risk of stroke, two stroke subtypes, and all-cause death. Higher SIRI, but not SII associated with increased MI incidence, and the association of SIRI was only significant in subjects aged <60.

This study aimed to identify the risk factors associated with intraventricular hemorrhage (IVH) in extremely preterm infants (EPIs), focusing on early-stage prediction to improve clinical outcomes. A retrospective cohort study was conducted at Guangzhou Women and Children’s Medical Center, including 189 EPIs born between January 2019 and December 2023. Infants were categorized into IVH and non-IVH groups based on head ultrasound findings. Risk factors were assessed using univariate and multivariate analyses, and a predictive model for IVH was developed. Of the 189 EPIs, 80 (42.3%) developed IVH, with 26 (13.8%) experiencing severe IVH. Gestational age was identified as a significant protective factor (OR = 0.565, p  = 0.023), while invasive mechanical ventilation (IMV) was a key risk factor (OR = 2.718, p  = 0.012). The predictive model demonstrated good performance, with an AUC of 0.753 (95% CI: 0.681–0.825). Gestational age and IMV are critical factors in the development of IVH in EPIs. Early identification of high-risk infants based on these factors can aid in timely interventions to reduce IVH incidence and improve outcomes.

Nitraria tangutorum Bobrov., belonging to the family Nitrariaceae, is a drought-tolerant and salt-loving plant and has drawn attention for its good economic and ecological value. As one of the main group species and dominant species in China’s desert and semi-desert regions, N. tangutorum possesses superior tolerance to drought, high temperature, cold, barren, high salinity and alkalinity and wind and sand. Its root system is well developed, with many branches and a strong germination capacity. Once buried in sandy soil, N. tangutorum can quickly produce a large number of adventitious roots, forming new plants and continuously expanding the shrubs, forming fixed and semi-fixed shrub sand dunes. Sand dune shrubs can trap and fix a large amounts of quicksand, prevent desert expansion and erosion, and play an important role in maintaining regional ecosystem balance and improving ecological environmental quality. In addition, the phytochemical screening studies report that N. tangutorum contains an abundance of various compounds including flavonoids, alkaloids, phenolic acids and polysaccharides. These compounds confer a range of beneficial bioactivities such as antioxidant, anti-inflammatory, anti-tumor, anti-fatigue, liver protection, neuroprotection, cardiovascular protection, lowering blood lipid, regulating blood sugar level and immunoregulation. The fruits of N. tangutorum also contain vitamin C, amino acids, minerals and microelements. It has been traditionally used as a nutritional food source and in folk medicine to treat diseases of the spleen and stomach, abnormal menstruation, indigestion, and hyperlipidemia. N. tangutorum , as a wild plant with medicinal and edible homology, possesses remarkable economic and medicinal values. This detailed, comprehensive review gathers and presents all the information related to the morphological structure, propagation characteristics, resistance physiology and exploitation and utilization of N. tangutorum , providing a theoretical basis for the researchers to conduct future in-depth research on N. tangutorum .

Uneven oxygen supply in solid tumors leads to hypoxic and normoxic regions. Hypoxic cells exhibit increased secretion of lactate, which creates an acidic tumor microenvironment (TME). This acidic TME is positively associated with tumor metastasis. Despite the increased metastatic capacity of hypoxic cells, they are located relatively further away from the blood vessels and have limited access to the circulatory system. Studies have shown that cancer stem cells (CSCs) are enriched for tumor metastasis-initiating cells and generally undergo aerobic respiration, which could be enhanced by lactate. We therefore hypothesized that TME-derived lactate may promote the metastasis of normoxic CSCs. In the present study, the abundance of hypoxic and normoxic CSCs was analyzed in primary CRC tumors. It was found that the proportion of normoxic CSCs was positively associated with tumor stage. Using two human CRC cell lines, LoVo and SW480, and a patient-derived xenograft (XhCRC), it was found that treatment with lactate promoted normoxic CSC metastasis. Metabolism analysis indicated that, upon treatment with lactate, oxidative phosphorylation (OXPHOS) activity in normoxic CSCs was enhanced, whereas hypoxic CSCs were rarely altered. At the molecular level, the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of lactate oxidation, was found to be elevated in normoxic CSCs. Furthermore, PGC-1α knockdown markedly reduced the metastatic potential of normoxic CSCs. Notably, both the PGC-1α-mediated OXPHOS activity and metastatic potential were impaired when hypoxia-inducible factor-1α (HIF-1α) was activated in normoxic CSCs. Together, these findings provide a therapeutic strategy against tumor metastasis through the targeting of PGC-1α and, thus, the suppression of lactate-feeding OXPHOS in normoxic CSCs may improve the therapeutic benefit of patients with cancer, particularly CRC.