C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse.

Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line-derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q-globular C1Q receptor recognition and subsequent stimulation of transforming growth factor ß1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

Identification of whole-genome mutations and structural variations of bile cell-free DNA in cholangiocarcinoma.

Bile cell-free DNA (cfDNA) has been reported as a promising liquid biopsy tool for cholangiocarcinoma (CCA), however, the whole-genome mutation landscape and structural variants (SVs) of bile cfDNA remains unknown. Here we performed whole-genome sequencing on bile cfDNA and analyzed the correlation between mutation characteristics of bile cfDNA and clinical prognosis. TP53 and KRAS were the most frequently mutated genes, and the RTK/RAS, homologous recombination (HR), and HIPPO were top three pathways containing most gene mutations. Ten overlapping putative driver genes were found in bile cfDNA and tumor tissue. SVs such as chromothripsis and kataegis were identified. Moreover, the hazard ratio of HR pathway mutations were 15.77 (95% CI: 1.571-158.4), patients with HR pathway mutations in bile cfDNA exhibited poorer overall survival (P = 0.0049). Our study suggests that bile cfDNA contains genome mutations and SVs, and HR pathway mutations in bile cfDNA can predict poor outcomes of CCA patients.

Electrochemically-driven actuators: from materials to mechanisms and from performance to applications.

Soft actuators, pivotal for converting external energy into mechanical motion, have become increasingly vital in a wide range of applications, from the subtle engineering of soft robotics to the demanding environments of aerospace exploration. Among these, electrochemically-driven actuators (EC actuators), are particularly distinguished by their operation through ion diffusion or intercalation-induced volume changes. These actuators feature notable advantages, including precise deformation control under electrical stimuli, freedom from Carnot efficiency limitations, and the ability to maintain their actuated state with minimal energy use, akin to the latching state in skeletal muscles. This review extensively examines EC actuators, emphasizing their classification based on diverse material types, driving mechanisms, actuator configurations, and potential applications. It aims to illuminate the complicated driving mechanisms of different categories, uncover their underlying connections, and reveal the interdependencies among materials, mechanisms, and performances. We conduct an in-depth analysis of both conventional and emerging EC actuator materials, casting a forward-looking lens on their trajectories and pinpointing areas ready for innovation and performance enhancement strategies. We also navigate through the challenges and opportunities within the field, including optimizing current materials, exploring new materials, and scaling up production processes. Overall, this review aims to provide a scientifically robust narrative that captures the current state of EC actuators and sets a trajectory for future innovation in this rapidly advancing field.

LncRNA FOXD1-AS1 regulates pancreatic cancer stem cell properties and 5-FU resistance by regulating the miR-570-3p/SPP1 axis as a ceRNA.

Cancer stem cells (CSCs) play a pivotal role in the pathogenesis of human cancers. Previous studies have highlighted the role of long non-coding RNA (lncRNA) in modulating the stemness of CSCs. In our investigation, we identified an upregulation of lncRNA FOXD1-AS1 in CSCs. The enforced expression of lncRNA FOXD1-AS1 promotes tumorigenesis and self-renewal in pancreatic cancer CSCs. Conversely, the knockdown of lncRNA FOXD1-AS1 inhibits tumorigenesis and self-renewal in pancreatic cancer CSCs. Furthermore, our findings reveal that lncRNA FOXD1-AS1 enhances self-renewal and tumorigenesis in pancreatic cancer CSCs by up-regulating osteopontin/secreted phosphoprotein 1(SPP1) and acting as a ceRNA to sponge miR-570-3p in pancreatic cancer (PC) CSCs. Additionally, lncRNA FOXD1-AS1 depleted pancreatic cancer cells exhibit heightened sensitivity to 5-FU-indued cell growth inhibition and apoptosis. Analysis of patient-derived xenografts (PDX) indicates that a low level of lncRNA FOXD1-AS1 may serve as a predictor of 5-FU benefits in PC patients. Moreover, the introduction of SPP1 can reverse the sensitivity of lncRNA FOXD1-AS1-knockdown PC cells to 5-FU-induced cell apoptosis. Importantly, molecular studies have indicated that the elevated levels of lncRNAFOXD1-AS1 in PC are facilitated through METTL3 and YTHDF1-dependent m6A methylation. In summary, our results underscore the critical functions of lncRNA FOXD1-AS1 in the self-renewal and tumorigenesis of pancreatic cancer CSCs, positioning lncRNA FOXD1-AS1 as a promising therapeutic target for PC.

Horizontal Transport in Ti3C2Tx MXene for Highly Efficient Osmotic Energy Conversion from Saline-Alkali Environments.

Osmotic energy from the ocean has been thoroughly studied, but that from saline-alkali lakes is constrained by the ion-exchange membranes due to the trade-off between permeability and selectivity, stemming from the unfavorable structure of nanoconfined channels, pH tolerance, and chemical stability of the membranes. Inspired by the rapid water transport in xylem conduit structures, we propose a horizontal transport MXene (H-MXene) with ionic sequential transport nanochannels, designed to endure extreme saline-alkali conditions while enhancing ion selectivity and permeability. The H-MXene demonstrates superior ion conductivity of 20.67 S m-1 in 1 M NaCl solution and a diffusion current density of 308 A m-2 at a 10-fold salinity gradient of NaCl solution, significantly outperforming the conventional vertical transport MXene (V-MXene). Both experimental and simulation studies have confirmed that H-MXene represents a novel approach to circumventing the permeability-selectivity trade-off. Moreover, it exhibits efficient ion transport capabilities, addressing the gap in saline-alkali osmotic power generation.

[Pay attention to the mental health of children with short stature]. / å ³æ³¨çŸ®èº«æå„¿ç«¥å¿ƒç†å¥åº·.

In the clinical diagnosis and treatment of children with short stature, mental health issues merit special attention. It is widely acknowledged that the psychological well-being of children with short stature is lower than that of their peers with normal height. Therefore, during the diagnosis, treatment, and care of short stature, it is crucial to actively monitor the mental health of these children, promptly identify potential psychological and behavioral issues, and intervene accordingly. Such measures play a positive role in enhancing the quality of life of these children and improving their physical and mental health. This article analyses and discusses the current state of psychological assessment and psycho-behavioral interventions for children with short stature, aiming to provide insights for improving their mental health.

Fe Single-Atom Catalyst for Efficient and Rapid Fenton-Like Degradation of Organics and Disinfection against Bacteria.

The Fenton-like reaction has great potential in water treatment. Herein, an efficient and reusable catalytic system is developed based on atomically dispersed Fe catalyst by anchoring Fe atoms on nitrogen-doped porous carbon (Fe SA/NPCs). The catalyst of Fe SA/NPCs exhibits enhanced performance in activating peroxymonosulfate (PMS) for organic pollutant degradation and bacterial inactivation. The Fe SA/NPCs + PMS system demonstrates a high turnover frequency of 39.31 min-1 in Rhodamine B (RhB) degradation as well as a strong bactericidal activity that can completely sterilize an Escherichia coli culture within 5 min. Meanwhile, the degradation activity of RhB by Fe SA/NPCs is improved up to 28 to 371-fold in comparison with the controls. Complete degradation of RhB can be achieved in 30 s by the Fe SA/NPCs + PMS system, demonstrating an efficiency much higher than most traditional Fenton-like processes. Experiments with different radical scavengers and density functional theory calculations have revealed that singlet oxygen (1 O2 ) generated on the N-coordinated single Fe atom (Fe-N4 ) sites is the key reactive species for the effective and rapid pollutant degradation and bacterial inactivation. This work innovatively affords a promising single-Fe-atom catalyst/PMS system for applying Fenton-like reactions in water treatment.

Long-term effects of mixed planting on arbuscular mycorrhizal fungal communities in the roots and soils of Juglans mandshurica plantations.

BACKGROUND: Establishing mixed plantations is an effective way to improve soil fertility and increase forest productivity. Arbuscular mycorrhizal (AM) fungi are obligate symbiotic fungi that can promote mineral nutrient absorption and regulate intraspecific and interspecific competition in plants. However, the effects of mixed plantations on the community structure and abundance of AM fungi are still unclear. Illumina MiSeq sequencing was used to investigate the AM fungal community in the roots and soils of pure and mixed plantations (Juglans mandshurica × Larix gmelinii). The objective of this study is to compare the differential responses of the root and rhizosphere soil AM fungal communities of Juglans mandshurica to long-term mixed plantation management. RESULTS: Glomus and Paraglomus were the dominant genera in the root samples, accounting for more than 80% of the sequences. Compared with that in the pure plantation, the relative abundance of Glomus was higher in the mixed plantation. Glomus, Diversispora and Paraglomus accounted for more than 85% of the sequences in the soil samples. The relative abundances of Diversispora and an unidentified genus of Glomeromycetes were higher and lower in the pure plantation, respectively. The Root_P samples (the roots in the pure plantation) had the highest number of unique OTUs (operational taxonomic units), which belonged mainly to an unidentified genus of Glomeromycetes, Paraglomus, Glomus and Acaulospora. The number of unique OTUs detected in the soil was lower than that in the roots. In both the root and soil samples, the forest type did not have a significant effect on AM fungal diversity, but the Sobs value and the Shannon, Chao1 and Ace indices of AM fungi in the roots were significantly higher than those in the soil. CONCLUSIONS: Mixed forest management had little effect on the AM fungal community of Juglans mandshurica roots and significantly changed the community composition of the soil AM fungi, but not the diversity.

Ultraviolet luminescence enhancement of planar wide bandgap semiconductor film by a hybrid microsphere cavity/dual metallic nanoparticles sandwich structure.

Here we report a novel hybrid structure composing of microsphere array (MA), Al nanoparticles (Al-NPs), ZnO thin film (luminescence layer), Au nanoparticles (Au-NPs), and substrate (sapphire) for ultraviolet (UV) luminescence enhancement of planar wide bandgap semiconductor film. The plasmonic sandwich structure of Al-NPs/ZnO/Au-NPs boosts the hot electron state density in the conduction band by electron trapping from deep-defect level of ZnO and localized surface plasmon resonances (LSPRs) coupling around dual metallic NPs, enhancing UV emission and suppressing visible emission efficiently. The dielectric microsphere array capping on the plasmonic sandwich structure further increases UV emission intensity via photonic nanojets, optical whispering-gallery modes (WGMs), and directional antenna effect, by which the interaction between photon and exciton is strengthened. The contribution of microsphere cavity coupling with LSPRs to UV luminescence enhancement is therefore revealed. The maximum enhancement ratio of up to two orders of magnitude (~250-fold) is achieved by the optimized 5.06-µm-diameter-MA/Al-NPs/ZnO/Au-NPs/sapphire structure and the UV emission is highly directional with a divergent angle of ~5°. The present work provides a simple and easily-prepared structure incorporating optical WGMs and LSPRs to manipulate UV luminescence of planar wide-bandgap semiconductors for potential optoelectronic applications.

REDUCTION OF PM2.5 TOXICITY ON HUMAN ALVEOLAR EPITHELIAL CELLS A549 BY TEA POLYPHENOLS.

Tea-derived polyphenols have anticancer and antioxidant properties, and they can regulate oxidative stress. This study was designed to quantify both the toxic effects of fine particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) and determine whether tea polyphenols could provide a protective effect against PM2.5 toxicity on human alveolar epithelial A549 cells in vitro. Cytotoxic effects of the PM2.5 on A549 cells were measured by means of cell viability, the expression of caspase-3, bax/bcl-2 and C/EBP-homologous protein (CHOP), and the generation of intracellular reactive oxygen species, malondialdehyde and superoxide dismutase. The results showed that tea polyphenols ameliorated some of the adverse effects of PM2.5 on A549 cell viability and superoxide dismutase levels. In addition, tea polyphenols decreased the production of reactive oxygen species, malondialdehyde generation, and apoptosis in response to PM2.5 exposure. Therefore, our results support a role for tea polyphenols in reducing the toxicity of PM2.5, particularly with regard to targeting oxidative stress and apoptosis.

Sandwich-structure-modulated photoluminescence enhancement of wide bandgap semiconductors capping with dielectric microsphere arrays.

Here we investigated the effect of substrate and film thickness on photoluminescence (PL) enhancement of wide bandgap semiconductor (i.e. ZnO) by dielectric microsphere array/luminescence film/substrate (MLS) sandwich structures. The PL enhancement channels in the sandwich structure were revealed, for the first time, including the focusing property of microsphere array (MSA) distinctly enhancing free-exciton recombination, anti-reflection effect of MSA increasing excitation cross-section area, MLS-supported TW-/SW-WGMs inducing ASE and Purcell's effect, and optical directional antenna effect for high equivalent NA of objective lens as well as out-coupling efficiency. The enhancement ratio of intensity (ERI) for ZnO UV-PL from free-exciton recombination in the sandwich structure was found to be strongly dependent upon the refractive index of substrate and luminescence film thickness. In order to achieve high ERI for PL emission, the refractive index of substrate should differ from luminescence film and the film thickness needs to be chosen to support WGMs in the sandwich structure. The maximum ERI beyond one order of magnitude for ZnO UV-PL was therefore predicted theoretically and validated experimentally, where 11.25-fold UV PL enhancement ratio was achieved in ~650-nm-thick ZnO film grown on SiC substrate and capped with 5.06-µm-diameter MSA. The ERI could further be increased by improving above-mentioned enhancement channels. The present work provides a novel platform to manipulate light by low-loss dielectric microstructures for enhancing photon-matter interaction, which would be employed for other semiconductors achieving energy-saving luminescence and high-sensitivity photoelectric detection in future.

[Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].

OBJECTIVE: To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. METHODS: A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. RESULTS: The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). CONCLUSIONS: Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

A prospective, double-blind, randomized controlled trial of treatment of atlantoaxial instability with C1 posterior arches >4 mm by comparing C1 pedicle with lateral mass screws fixation.

BACKGROUND: C1 posterior arch screw placement is one of the most effective treatments for atlantoaxial instability (AAI), which can be performed by either pedicle or lateral mass screw fixation. This study attempted to compare the feasibility and clinical outcomes of C1 pedicle with lateral mass screw fixations for treatment of AAI with C1 posterior arches >4 mm. METHODS: A total of 140 patients with AAI (C1 posterior arches measuring >4 mm) was enrolled in this single-center, randomized, double-blind trial. The subjects were randomly assigned into two treatments: C1 pedicle (group A) or lateral mass (group B) screw fixation. The patients, independent evaluating physicians and radiologists were blinded throughout the entire study. Patients were assessed before operation and in a series of follow-ups at 6 weeks, 6 months, 1 year, and 3 years post-surgery. The operation time, volume of blood loss, intraoperative complications, bone fusion rates, Japanese Orthopaedic Association (JOA) and visual analog scale (VAS) scores were monitored. RESULTS: All 140 patients showed overall improvements in clinical symptoms after surgery. The mean follow-up time was 24.5 ± 13.0 months. In both groups, the mean JOA scores improved significantly at the time of final follow-up as compared to prior surgery (group A: 7.1 ± 1.4 vs 13.7 ± 1.9; group B:7.3 ± 1.8 vs 13.1 ± 1.4; improvement rates: 87.2% (group A) and 86.5% (group B)). The VAS scores also decreased significantly in both groups at the time of final follow-up as compared to prior surgery (group A: 6.0 ± 1.3 vs 1.7 ± 0.8, and group B: 5.7 ± 1.1 vs 2.1 ± 1.2). Bone fusion was achieved within 12 months postoperatively in the patients from both groups. The operation time was significantly shorter and volume of blood loss was significantly less in the patients from group A as compared to group B (p < 0.01). Furthermore, thirteen patients had burst bleeding from the C1-2 venous plexus and nine patients had immediate pain and numbness in the occipitocervical region due to C2 nerve roots irritation during lateral mass screw replacement, which were not observed in the patients with C1 pedicle screw insertion. No complications such as screw loosening, shifting, breakage, or AAI were observed in both groups. CONCLUSIONS: C1 pedicle screw fixation is less invasive and simpler, and has fewer complications. It renders better clinical outcomes than lateral mass screw fixation for treatment of AAI. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-IOR-15006748 .

Inhibitory effects of soil biota are ameliorated by high plant diversity.

The idea that plant communities with high species diversity are more stable, productive, and resistant to invasion at small spatial scales has become an important ecological paradigm. Recently, the role of soil biota has emerged as a major driver of this relationship between plant species diversity and ecosystem function. In greenhouse experiments, we found that soil collected from experimentally constructed species-rich plant assemblages (that originally contained between 10 and 16 species) promoted the growth of 4 native target plant species more than soil from species-poor communities (that originally contained between 2 and 5 species). Sterilization of soils from species-poor communities improved the growth of these target species more than sterilization of soils from species-rich plant communities, indicative that inhibitory soil biota had greater negative impacts on plant growth in low versus high diversity soils. These results suggest that strong soil biota effects in soils do not simply accrue in experimental monocultures, but can occur in low diversity assemblages that are more realistic of what occurs in nature. Our findings suggest a mechanistic explanation for the diversity-productivity relationship, and further support the importance of inhibitory soil biota as significant contributors to spatial and temporal patterns of abundance in natural plant communities through negative plant-soil feedback.

Performance and strategy comparisons of human listeners and logistic regression in discriminating underwater targets.

To improve the design of underwater target recognition systems based on auditory perception, this study compared human listeners with automatic classifiers. Performances measures and strategies in three discrimination experiments, including discriminations between man-made and natural targets, between ships and submarines, and among three types of ships, were used. In the experiments, the subjects were asked to assign a score to each sound based on how confident they were about the category to which it belonged, and logistic regression, which represents linear discriminative models, also completed three similar tasks by utilizing many auditory features. The results indicated that the performances of logistic regression improved as the ratio between inter- and intra-class differences became larger, whereas the performances of the human subjects were limited by their unfamiliarity with the targets. Logistic regression performed better than the human subjects in all tasks but the discrimination between man-made and natural targets, and the strategies employed by excellent human subjects were similar to that of logistic regression. Logistic regression and several human subjects demonstrated similar performances when discriminating man-made and natural targets, but in this case, their strategies were not similar. An appropriate fusion of their strategies led to further improvement in recognition accuracy.

Associations between special diet and incidence risk of osteoporosis: a Mendelian randomization study.

Introduction: Osteoporosis is a prevalent challenge in clinical orthopedics, affecting a significant percentage of individuals aged 50 and above. The goal of this study was to comprehensively understand the relationships between a specialized dietary regimen and the risk of developing osteoporosis. Methods: This study employed extensive genome-wide association study (GWAS) summary statistics derived from the UK Biobank. It encompassed 8 kinds of special diets and 7 datasets pertaining to osteoporosis and associated symptoms. The principal analytical approach employed was the inverse-variance weighted method. Additionally, sensitivity analysis was employed to elucidate the diverse multiplicity patterns observed in the final model. Results: Our results showed that there is significant evidence that a gluten-free diet is associated with osteoporosis [odds ratio (OR): 1.080, 95% confidence interval (CI): 1.048-1.112, p = 4.23E-07)]. Furthermore, there exists a suggestive link between the three distinct dietary approaches and osteoporosis [(OR: 0.949, 95%CI: 0.929-0.970, p = 3.00E-06) for comprehensive consumption; (OR: 1.053, 95%CI: 1.018-1.089, p = 2.23E-03) for abstaining from wheat consumption; (OR: 1.036, 95%CI: 1.005-1.068, p = 1.97E-02) for abstaining from sugar consumption]. No additional correlation between the special dietary regimens and osteoporosis has been observed. Conclusion: Our research has uncovered a notable correlation between a gluten-free diet and the occurrence of osteoporosis. Furthermore, it exerts a promoting influence on the onset of osteoporosis, which stands in direct contradiction to the therapeutic principles for Celiac Disease's complications. As such, a novel association among these three elements is postulated.

Emerging innovations in electrically powered artificial muscle fibers.

This review systematically explores the inherent structural advantages of fiber over conventional film or bulk forms for artificial muscles, emphasizing their enhanced mechanical properties and actuation, scalability, and design flexibility. Distinctive merits of electrically powered artificial muscle fiber actuation mechanisms, including electrothermal, electrochemical and dielectric actuation, are highlighted, particularly for their operational efficiency, precise control capabilities, miniaturizability and seamless integration with electronic components. A comprehensive overview of significant research driving performance enhancements in artificial muscle fibers through materials and structural innovations is provided, alongside a discussion of the diverse design methodologies that have emerged in this field. A detailed comparative assessment evaluates the performance metrics, advantages and manufacturing complexities of each actuation mechanism, underscoring their suitability for various applications. Concluding with a strategic outlook, the review identifies key challenges and proposes targeted research directions to advance and refine artificial muscle fiber technologies.

Exploring traditional Chinese medicine as a potential treatment for sarcopenia: A network pharmacology and data mining analysis of drug selection and efficacy.

Sarcopenia, as an increasingly pressing clinical issue, can be ameliorated through employment of traditional Chinese medicines. However, the current lack of specific pharmacological interventions for Sarcopenia necessitates further exploration of novel possibilities in traditional Chinese medicine for the treatment of this condition, utilizing advanced methodologies such as web pharmacology and data mining. Screening the essential targets of Sarcopenia, conducting matching between target and active molecules, as well as active molecules and herbs. Employing data mining techniques to analyze the screening outcomes, and molecular docking to compare the binding activities of active molecules with target proteins. The approach of using herbs for the treatment of Sarcopenia involves 13 targets, with 414 active compounds and 367 types of herbs. Data mining reveals that the herbs used in treating Sarcopenia are primarily characterized by their bitter taste, exerting their effects through dispelling dampness and promoting blood circulation. Moreover, 2 new formulas are postulated. Furthermore, molecular docking analysis indicates that the main active components of the herbs can be observed to tightly bind with the targets. Through network pharmacology and molecular docking, our findings reveal that herbs contain 15 key active components and 5 key targets, which correspond to 7 major herbs and 2 new formulas. Academically, these findings hold significant reference value for the development of novel drugs targeting Sarcopenia.

LincRNA PRNCR1 activates the Wnt/ß-catenin pathway to drive the deterioration of hepatocellular carcinoma via regulating miR-411-3p/ZEB1 axis.

Hepatocellular carcinoma (HCC) is an intractable malignant disease with high incidence rate annually. LincRNA PRNCR1 has been confirmed as a tumor supporter, while its functions in HCC remain unclear. This study aims to explore the mechanism of LincRNA PRNCR1 in hepatocellular carcinoma. The qRT-PCR was applied to the quantification of non-coding RNAs. Cell counting Kit-8 (CCK-8), Transwell assay and flow cytometry assay were applied to reflect the change in the phenotype of HCC cells. Moreover, the databases including Targetscan and Starbase and dual-luciferase reporter assay were applied to investigate the interaction of the genes. The western blot was applied to detect the abundance of proteins and the activity of the related pathways. Elevated LincRNA PRNCR1 was dramatically upregulated in HCC pathological samples and cell lines. MiR-411-3p served as a target of LincRNA PRNCR1, and decreased miR-411-3p was found in the clinical samples and cell lines. LincRNA PRNCR1 downregulation could induce the expression of miR-411-3p, and LincRNA PRNCR1 silence could impede the malignant behaviors via increasing the abundance of miR-411-3p. Zinc finger E-box binding homeobox 1 (ZEB1) was confirmed as a target of miR-411-3p, which remarkably upregulated in HCC cells, and ZEB1 upregulation could significantly rescue the effect of miR-411-3p on malignant behaviors of HCC cells. Moreover, LincRNA PRNCR1 was confirmed to involve the Wnt/ß-catenin pathway via regulating miR-411-3p/ZEB1 axis. This study suggested that LincRNA PRNCR1 could drive the malignant progression of HCC via regulating miR-411-3p/ZEB1 axis.

The diversified role of mitochondria in ferroptosis in cancer.

Ferroptosis is a form of regulated cell death induced by iron-dependent lipid peroxidation, and it has been studied extensively since its discovery in 2012. Induced by iron overload and ROS accumulation, ferroptosis is modulated by various cellular metabolic and signaling pathways. The GSH-GPX4 pathway, the FSP1-CoQ10 pathway, the GCH1-BH4 pathway, the DHODH-CoQH2 system and the sex hormones suppress ferroptosis. Mitochondrial iron metabolism regulates ferroptosis and mitochondria also undergo a morphological change during ferroptosis, these changes include increased membrane density and reduced mitochondrial cristae. Moreover, mitochondrial energy metabolism changes during ferroptosis, the increased oxidative phosphorylation and ATP production rates lead to a decrease in the glycolysis rate. In addition, excessive oxidative stress induces irreversible damage to mitochondria, diminishing organelle integrity. ROS production, mitochondrial membrane potential, mitochondrial fusion and fission, and mitophagy also function in ferroptosis. Notably, some ferroptosis inhibitors target mitochondria. Ferroptosis is a major mechanism for cell death associated with the progression of cancer. Metastasis-prone or metastatic cancer cells are more susceptible to ferroptosis. Inducing ferroptosis in tumor cells shows very promising potential for treating drug-resistant cancers. In this review, we present a brief retrospect of the discovery and the characteristics of ferroptosis, then we discuss the regulation of ferroptosis and highlight the unique role played by mitochondria in the ferroptosis of cancer cells. Furthermore, we explain how ferroptosis functions as a double-edged sword as well as novel therapies aimed at selectively manipulating cell death for cancer eradication.