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Shale oil is mainly stored in the nano–micro-pores of shale in the form of adsorption or in a free state. Among them, only free-state oil is the main contributor to shale oil production under natural elastic energy. Therefore, it is crucial to evaluate the movability of crude oil effectively. In this paper, focusing on the Jurassic shale oil reservoir core in the middle-eastern Sichuan region of China, low-field nuclear magnetic resonance (NMR) technology is used to analyze the basic characteristics of shale oil core samples. Experiments on the low-field NMR one-dimensional and two-dimensional spectrum characteristics of the original core, heat-treated core, and thermogravimetric-treated shale core are carried out. The effects of the TG-MS method, T2 method, and the volatilization of light oil components on the movability of shale oil reservoirs are analyzed, and the movability characteristics of shale oil reservoirs in the middle-eastern Sichuan region are preliminarily clarified. The results show that under thermal treatment, the distribution range of the two-dimensional spectrum of the core oil occurrence area is significantly reduced, and the T1 and T2 distribution ranges are reduced by 10.9% and 60.7%, respectively. According to the TG-MS method, the mobile oil, bound oil, and adsorbed oil account for 74.7%, 8.1%, and 17.2%, respectively. The quantitative calculation of movable oil saturation by NMR combined with heat treatment is 65.6%, which is lower than that calculated using the thermogravimetric method. In order to calculate the movability more accurately, the scale effect between different samples should be considered. This study could provide a theoretical basis for the subsequent shale oil development program.

Summary: N(6)-methyladenosine (m6A) critically regulates RNA dynamics in various biological processes. The m6A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, thereby stabilizing this transcript. Unexpectedly, LATS2 depletion suppresses glioblastoma stem cell self-renewal independent of yes-associated protein activation. Additionally, deficiency in either LATS2 or ALKBH5 phosphorylation impedes tumor progression in mouse xenograft models. Moreover, high levels of LATS2 expression and ALKBH5 phosphorylation are associated with tumor malignancy in patients with gliomas. Collectively, our study unveils an oncogenic positive feedback loop between LATS2 and ALKBH5, revealing a non-canonical branch of the Hippo pathway for RNA processing and suggesting potential anti-cancer interventions.

Objectives: Many studies have investigated aberrant functional connectivity (FC) using resting-state functional MRI (rs-fMRI) in subjective tinnitus patients. However, no studies have verified the efficacy of resting-state FC as a diagnostic imaging marker. We established a convolutional neural network (CNN) model based on rs-fMRI FC to distinguish tinnitus patients from healthy controls, providing guidance and fast diagnostic tools for the clinical diagnosis of subjective tinnitus. Methods: A CNN architecture was trained on rs-fMRI data from 100 tinnitus patients and 100 healthy controls using an asymmetric convolutional layer. Additionally, a traditional machine learning model and a transfer learning model were included for comparison with the CNN, and each of the three models was tested on three different brain atlases. Results: Of the three models, the CNN model outperformed the other two models with the highest area under the curve, especially on the Dos_160 atlas (AUC = 0.944). Meanwhile, the model with the best classification performance highlights the crucial role of the default mode network, salience network, and sensorimotor network in distinguishing between normal controls and patients with subjective tinnitus. Conclusion: Our CNN model could appropriately tackle the diagnosis of tinnitus patients using rs-fMRI and confirmed the diagnostic value of FC as measured by rs-fMRI.

Although the immune factor interferon gamma-inducible protein 30 (IFI30) has been linked to the growth and immune infiltration of various malignancies, its function and mechanism in clear cell renal cell carcinoma (ccRCC) remains unclear. We used several databases to detect and validate IFI30 expression in ccRCC and its connection to immune invasion. We found that IFI30 expression was higher in ccRCC tissues compared to normal tissues, and was strongly associated with tumor grade, T stage, and M stage. Univariate and multivariate analyses showed that ccRCC cases with lower IFI30 expression levels had a higher OS rate than those with high IFI30 expression (P < 0.05). Additionally, we collected a total of 104 cases of ccRCC and adjacent tissues from the First Affiliated Hospital of Jinzhou Medical University between January 2018 and January 2020 for immunohistochemical (IHC) analysis, along with their relevant clinicopathological data. The relationship between IFI30 and expression of CD3E, CD4, CD8A, interleukin 10 (IL-10) and transforming growth factor beta (TGFB2) was examined using the ccRCC data from The Cancer Genome Atlas (TCGA) database, with findings verified by IHC analysis using the collected cases. Statistical analysis performed with SPSS found the positive correlation between the expression of CD3E, CD4, CD8A and IL-10 and the IFI30 expression, and negative correlation of TGFB2 expression with the IFI30 expression in ccRCC. Concurrently, a notable association was observed between high IFI30 expression and immune cell infiltration in ccRCC. High IFI30 expression is connected to the ccRCC's poor prognosis with the infiltration of immune cell. These findings suggest that high IFI30 expression could serve as a marker of poor prognosis and be associated with immune cell infiltration in ccRCC.

Summary: Recent studies have elucidated Nr5a2’s role in activating zygotic genes during early mouse embryonic development. Subsequent research, however, reveals that Nr5a2 is not critical for zygotic genome activation but is vital for the gene program between the 4- and 8-cell stages. A significant gap exists in experimental evidence regarding its function during the first lineage differentiation’s pivotal period. In this study, we observed that approximately 20% of embryos developed to the blastocyst stage following Nr5a2 ablation. However, these blastocysts lacked inner cell mass (ICM), highlighting Nr5a2’s importance in first lineage differentiation. Mechanistically, using RNA sequencing and CUT&Tag, we found that Nr5a2 transcriptionally regulates ICM-specific genes, such as Oct4, to establish the pluripotent network. Interference with or overexpression of Nr5a2 in single blastomeres of 2-cell embryos can alter the fate of daughter cells. Our results indicate that Nr5a2 works as a doorkeeper to ensure ICM formation in mouse blastocyst.

With the development of landslide monitoring system, many attempts have been made to predict landslide failure-time utilizing monitoring data of displacements. Classical models (e.g., Verhulst, GM (1,1), and Saito models) that consider the characteristics of landslide displacement to determine the failure-time have been investigated extensively. In practice, monitoring is continuously implemented with monitoring data-set updated, meaning that the predicted landslide life expectancy (i.e., the lag between the predicted failure-time and time node at each instant of conducting the prediction) should be re-evaluated with time. This manner is termed “dynamic prediction”. However, the performances of the classical models have not been discussed in the context of the dynamic prediction yet. In this study, such performances are investigated firstly, and disadvantages of the classical models are then reported, incorporating the monitoring data from four real landslides. Subsequently, a more qualified ensemble model is proposed, where the individual classical models are integrated by machine learning (ML)-based meta-model. To evaluate the quality of the models under the dynamic prediction, a novel indicator termed “discredit index (β)” is proposed, and a higher value of β indicates lower prediction quality. It is found that Verhulst and Saito models would produce predicted results with significantly higher β, while GM (1,1) model would indicate results with the highest mean absolute error. Meanwhile, the ensemble models are found to be more accurate and qualified than the classical models. Here, the performance of decision tree regression-based ensemble model is the best among the various ML-based ensemble models.

Purpose: In this study, we examined the current status of myopia among primary and secondary school children in northeastern Sichuan to analyze the factors connected to myopia and provide data support and a theoretical foundation for the prevention and control of myopia. Methods: Using a cross-sectional study and a comprehensive sampling survey, 34,138 students aged 5–19 years were screened for refraction in 22 primary and secondary schools in Langzhong, and 4000 behavioral questionnaires were delivered at random. After evaluation and rational problem-solving, a total of 3764 valid questionnaires were obtained. SPSS 23.0 statistical software was used for data analysis. Results: The percentage of myopia among primary and secondary school students in Langzhong was 65.61%, with female students having a higher rate than male students (P < 0.05); 52.81% of primary school students, 86.26% of secondary school students, and 88.17% of high school students had myopia. The incidence of myopia detection increased with school age (P < 0.001), indicating a correlation between age and myopia prevalence. The prevalence of myopia was mainly low (40.53%) and moderate myopia (19.89%). The prevalence of high myopia (5.19%) was relatively high. The prevalence of myopia among female students (5.54%) was greater than that in male students (P < 0.05) and increased with age (P < 0.001). The proportion of students who wore eyeglasses was 24.36%, with a larger proportion of female students (25.93%) than male students (22.61%) (P < 0.001). In addition, the rate of eyeglass use increased with school age (P < 0.001). A logistic regression analysis revealed that higher grade point averages, female gender, and long-term usage of electronic items were risk factors for myopia. The results of the questionnaire survey revealed that students in this region were under immense pressure to perform well academically, spent a lot of time engaged in near-work activities, and had a low rate of myopia awareness; 24.43% of the students had not had a vision examination in the previous year, indicating that parents did not pay sufficient attention to eye health. Conclusion: The incidence of myopia among children and teenagers is high in Northeast Sichuan, and the outlook for addressing the problem is bleak. Therefore, it is critical to improve vision monitoring and eye health education.

As urbanization and industrialization accelerate, China’s water resources are facing the double dilemma of inefficient utilization and serious pollution. This research employs the fixed effect difference-in-differences (DID) model to examine the impact of the country’s industrial wastewater emission reduction policy in the pilot city for a water ecological civilization (PCWEC). The findings indicate after PCWEC implementation in 2013 that there was a notable decrease in the discharge of industrial wastewater in pilot cities compared to non-pilot cities, and that the policy’s effectiveness exhibited a significant strengthening trend from 2014 to 2018. However, the interaction of total population, population density, fixed assets, regional GDP, total water resources, and proportion of the secondary industry in GDP has greatly weakened the policy’s effect. Regional results show that compared to the east and central regions, the policy effect in the west region is more significant, whereby the gap between pilot cities and non-pilot cities in the east and central regions is narrowing. To expedite the construction of water ecological civilization in China, it is necessary to comprehensively strengthen the management of water conservation and formulate industrial structure policies according to local conditions.

Sound diffusion performance is considered as an important issue in building acoustics. A well-diffused sound field can effectively enhance the human listening experience. In this context, inspired by Fresnel lenses in optics, we design a sub-wavelength acoustic metasurface (termed “Fresnel acoustic reflector”) to achieve broadband uniform diffuse reflections. To this end, an optimization strategy that combines Monte-Carlo search and other derivative-free algorithms is proposed to ensure, as far as possible, a global optimum for the objective function when dealing with the multi-peak problem encountered in complex sound fields. Numerical simulations show that the average normalized diffusion coefficient of the designed Fresnel reflector can reach up to 0.6 in the sub-wavelength frequency range 500–3400 Hz, which exhibits a better broadband diffusion performance compared to the traditional Schroeder diffusers. The simulated sound pressure field is also verified by experimental measurements. From a general perspective, the proposed optimization strategy and simulation framework can benefit the design of interior components in building acoustics.

Dichlorodiphenyltrichloroethane (DDT) is a broad-spectrum insecticide, widely detected in environments due to its high stability characteristic and long natural half-life period. The adverse impact of DDT exposure on organisms and humans has attracted great concern worldwide. The current study explored the developmental and neurobehavioral toxicity response of DDT in embryonic zebrafish. The embryos were treated with DDT (0, 0.1, 1, 2.5 and 5 µM) during 6 h post fertilization (hpf) to 144 hpf. Our result indicated that DDT exposures increased the embryo hatching rate at 48 and 60 hpf, the larval malformation rate at 120 hpf and mortality rate at 144 hpf. The manifested malformations included uninflated swim bladder, bent spine and tail, deformed liver, and pericardial edema. The 120 hpf larval organs size of the gut and swim bladder was decreased in higher exposed concentration groups. Besides, DDT exposure resulted in hyperactivity for the embryo spontaneous movement at 24 hpf and tremor like movement measured by the free larval activity at 72 hpf, as well as the larval activity at 96 hpf under light-dark transition stimulus. Mechanistic examinations at 120 hpf revealed DDT exposure elevated oxidative stress through MDA formation increase, ATP level decrease as well as antioxidant enzyme genes (sod1 and gpx1a) expression decrease. DDT exposure induced abnormal neurotransmitters expression with DA level increase, 5-HT and NOS level decrease. DDT exposure suppressed the gene expressions involved in axon development (rab33a and nrxn2a) and potassium channel (kcnq2 and kcnq3). Our results suggest that the hyperactivity and tremor like movement in DDT-exposed embryos/larvae may result from oxidative stress involved with neuronal damage.

BackgroundBased on CDC estimates in the United States, the prevalence of obesity was 42.4% in 2017-2018, and the annual cost of obesity was $147 billion in 2008. Yet studies estimate that only 20-40% of adults with obesity received counseling from their primary care providers. Recent studies using shared medical appointments (SMA), where patients are seen by a multidisciplinary team, have shown promising results in obesity management. We developed an insurance-based weight loss program incorporating SMA, called the Program for Reducing Obesity (PRO), and report our findings here.MethodsEnrollment began in January 2019 at the UCLA Health Thousand Oaks clinic. Patients age ≥18 years with BMI ≥30 kg/m2 were eligible by referral to PRO, a program consisting of individual visits and SMAs with an obesity medicine board certified endocrinologist and registered dietitian. Primary outcomes were change in weight after 3, 6, and 12 months. Secondary outcomes included proportion that achieved ≥5% weight loss, change in percent body fat, HbA1c, HDL, triglycerides, and blood pressure.Results102 patients (mean age 59.7 years, 72% women, mean weight 103.6 kg, mean BMI 36.6 kg/m2) have been analyzed, with 91 patients completing at least 12 months of the program. Patients achieved significant weight loss: 3.0%, 5.0%, and 7.8% of their baseline weight after 3, 6, and 12 months respectively. 52% of patients lost ≥5% of their baseline weight after 12 months. Patients had significant reductions in body fat: 2.1%, 7.4%, and 6.7% of their baseline (all p ≤ 0.01) after 3, 6, and 12 months respectively. Improvements were also seen in HbA1c (p ≤ 0.01), triglycerides (p ≤ 0.04), and systolic blood pressure (p ≤ 0.07) after 12 months although not all results achieved statistical significance.ConclusionOur institutional review of PRO, an insurance-based obesity program utilizing SMA, demonstrates a successful approach to promoting weight loss in a community-based setting.

Abstract Objective To improve the quality of community nursing teaching practice and cultivate undergraduate nursing students who meet the quality accreditation standards of our nursing profession, and to explore the establishment of an undergraduate nurse practice model. Methods Using the methods of literature review, survey, expert consultation, and discussion, we established the steps and contents of community practice teaching for undergraduate nursing students, and implemented them for the students of Grades 2014, 2015, and 2016, and evaluated the “community-hospital-community” practice model through various forms, such as student self-evaluation, faculty evaluation, exit examination, and evaluation by certified experts. Result A three-stage community nursing practice model of “community-hospital-community” was established for undergraduate nursing students. After three stages of practice, nursing undergraduates successfully passed the practical assessments and achieved excellent grades in each stage that met the requirements of the training program. In the first stage (community probation), community probation emphasizes a fundamental understanding of the community, using free clinics, health education, and home visits as entry points to effectively cultivate students’ job competence and proficiency in nursing operations and nurse-patient communication skills. In the second stage (internship in the hospital), through nursing internships in various systems, students are trained to integrate theoretical knowledge with practical skills and consolidate their understanding of fundamental knowledge, theory, and techniques. They are capable of preventing, diagnosing, intervening, and providing health education for common, frequent, urgent and critical complications in various clinical systems. They can formulate nursing plans and implement whole-person care. In the third stage (returning to the community for internship), students can master basic skills such as nursing operations and patient communication skills, and then they can enter the community internship. Conclusion The community nursing practice model of “community- hospital- community” for undergraduate nursing students can systematically train undergraduate nursing students’ ability to work in the community.

Abstract Background Zymomonas mobilis is an important industrial bacterium ideal for biorefinery and synthetic biology studies. High-throughput CRISPR-based genome editing technologies have been developed to enable targeted engineering of genes and hence metabolic pathways in the model ZM4 strain, expediting the exploitation of this biofuel-producing strain as a cell factory for sustainable chemicals, proteins and biofuels production. As these technologies mainly take plasmid-based strategies, their applications would be impeded due to the fact that curing of the extremely stable plasmids is laborious and inefficient. Whilst counterselection markers have been proven to be efficient for plasmid curing, hitherto only very few counterselection markers have been available for Z. mobilis. Results We constructed a conditional lethal mutant of the pheS gene of Z. mobilis ZM4, clmPheS, containing T263A and A318G substitutions and coding for a mutated alpha-subunit of phenylalanyl-tRNA synthetase to allow for the incorporation of a toxic analog of phenylalanine, p-chloro-phenylalanine (4-CP), into proteins, and hence leading to inhibition of cell growth. We demonstrated that expression of clmPheS driven by a strong P gap promoter from a plasmid could render the Z. mobilis ZM4 cells sufficient sensitivity to 4-CP. The clmPheS-expressing cells were assayed to be extremely sensitive to 0.2 mM 4-CP. Subsequently, the clmPheS-assisted counterselection endowed fast curing of genome engineering plasmids immediately after obtaining the desired mutants, shortening the time of every two rounds of multiplex chromosome editing by at least 9 days, and enabled the development of a strategy for scarless modification of the native Z. mobilis ZM4 plasmids. Conclusions This study developed a strategy, coupling an endogenous CRISPR-based genome editing toolkit with a counterselection marker created here, for rapid and efficient multi-round multiplex editing of the chromosome, as well as scarless modification of the native plasmids, providing an improved genome engineering toolkit for Z. mobilis and an important reference to develope similar genetic manipulation systems in other non-model organisms.

Abstract Background The aim of this study was to explore the function and mechanism of circular RNA (circRNA) matrix metallopeptidase 1 (circMMP1) in the progression of esophageal squamous cell carcinoma (ESCC). Methods CircMMP1 expression was detected by quantitative real‐time PCR (qRT‐PCR), and its relationship with the prognosis of ESCC patients was evaluated by Kaplan–Meier analysis. Cells were transfected using corresponding plasmids, and the cell proliferation activity, migration and invasion capabilities in vitro were assessed. The protein level in tissues and cells was analyzed using western blotting. RNA pulldown, dual‐luciferase reporter assay and RNA immunoprecipitation assay were performed in ESCC cells to detect the interaction between circMMP1 and miR‐671‐5p, or the correlation between miR‐671‐5p and ANO1. Xenograft tumor experiment was carried out to uncover the function of circMMP1 in vivo. Results The high level of circMMP1 in tumor tissues was associated with poor prognoses of ESCC patients. Knockdown of circMMP1 suppressed ESCC cell proliferation, migration and invasion in vitro. MiR‐671‐5p was the target of circMMP1 and mediated the inhibition effect of circMMP1 on ESCC cells. CircMMP1 targeted miR‐671‐5p to regulate ANO1 expression, which was downstream of miR‐671‐5p. Overexpression of ANO1 weakened tumor‐repressive function of circMMP1 knockdown in ESCC cells. Moreover, silencing of circMMP1 impeded ESCC tumor growth in vivo. Conclusion Our study provided novel evidence that circMMP1 accelerated ESCC progression by acting as a miR‐671‐5p sponge to enhance ANO1 expression.

Background Promoting appropriate health technology to rural and urban communities is an important measure to improve the technical level and service capacity of primary care institutions. The First Affiliated Hospital of Xinjiang Medical University carried out the promotion of appropriate health technology in southern Xinjiang. Objective To evaluate the effect of appropriate technology promotion for stroke rehabilitation in southern Xinjiang, understand the needs of rehabilitation workers in southern Xinjiang for appropriate technology promotion for stroke rehabilitation and the goals they hope to achieve by participating in appropriate technology promotion for stroke rehabilitation projects, providing a basis for health administrative departments to implement appropriate rehabilitation technology promotion work. Methods The rehabilitation workers from the rehabilitation medicine departments of 8 people's hospitals, affiliated township health centers and communities health centers, federation of the disabled, civil affairs system and other rehabilitation institutions in 8 deep poverty-stricken counties which were considered as sample source sites by using a multi-stage sampling method in July 2018. The appropriate technology promotion for stroke rehabilitation was performed followed by a investigation by using self-designed questionnaire. The monthly outpatient volume, hospitalization volume and treatment income of the rehabilitation medicine department of people's hospitals before (January 1, 2018 to June 30, 2018) and after participation (July 1, 2020 to December 31, 2020) in technology promotion for stroke rehabilitation projects were compared. Results The appropriate technology promotion for stroke rehabilitation in acute, subacute and convalescent stages, as well as community and family rehabilitation of stroke was performed from January 1, 2018 to June 30, 2018, involving motor function rehabilitation training, functional electrical stimulation, mandatory exercise therapy techniques, constraint induced movement therapy (CIMT) , mirror therapy, management and rehabilitation training of dysphagia, daily living activities training and rehabilitation care of stroke patient. A total of 384 valid questionnaires were collected. Among the 384 rehabilitation workers, 63.3% (243/384) identified the appropriate technology promotion within districts (counties) as very meaningful; 46.1% (177/384) thought the project was very applicable in their local area; 37.5% (144/384) believed that the technology for stroke rehabilitation can be carried out in their medical institutions with a slight improvement of the relevant conditions; 46.9% (180/384) believed that the difficulty level of the appropriate technology promotion project was easy in terms of operation skills; after the training, 42.2% (162/384) claimed to be knowledgeable about the technology and need to learn and receive further training. The monthly outpatient volume and monthly treatment income of the rehabilitation medicine department of people's hospitals after participating in stroke rehabilitation technology promotion projects increased significantly compared with before participation (P

Abstract Background Glioma is a lethal brain cancer and lacking effective therapies. Challenges include no effective therapeutic target, intra- and intertumoral heterogeneity, inadequate effective drugs, and an immunosuppressive microenvironment, etc. Deciphering the pathogenesis of gliomas and finding out the working mechanisms are urgent and necessary for glioma treatment. Identification of prognostic biomarkers and targeting the biomarker genes will be a promising therapy. Methods From our RNA-sequencing data of the oxidative phosphorylation (OXPHOS)-inhibition sensitive and OXPHOS-resistant cell lines, we found that the scaffolding protein caveolin 1 (CAV1) is highly expressed in the resistant group but not in the sensitive group. By comprehensive analysis of our RNA sequencing data, Whole Genome Bisulfite Sequencing (WGBS) data and public databases, we found that CAV1 is highly expressed in gliomas and its expression is positively related with pathological processes, higher CAV1 predicts shorter overall survival. Results Further analysis indicated that (1) the differentiated genes in CAV1-high groups are enriched in immune infiltration and immune response; (2) CAV1 is positively correlated with tumor metastasis markers; (3) the methylation level of CAV1 promoters in glioma group is lower in higher stage than that in lower stage; (4) CAV1 is positively correlated with glioma stemness; (5) higher expression of CAV1 renders the glioma cells’ resistant to oxidative phosphorylation inhibitors. Conclusion Therefore, we identified a key gene CAV1 and deciphered its function in glioma progression and prognosis, proposing that CAV1 may be a therapeutic target for gliomas. Graphical Abstract

Abstract Background Invisalign First System (First) is a new type of orthodontic appliance for maxillary arch expansion in mixed dentition children. Till now, few studies have evaluated the expansion effects of First versus other appliances. What’s more, most studies of arch expansion did not include a natural group to rule out growth effects. This prospective cohort study aimed to evaluate the dental and dentoalveolar effects using First or acrylic splint rapid maxillary expander (RME) in adolescents excluding growth factors. Materials and methods After screening by strict inclusion criteria and propensity score matching (PSM), fifty-one patients were included: First group (n = 17), RME group (n = 17), and natural growth (NG) group (n = 17). Nine indicators including dental arch width, dentoalveolar arch width, and inclination of the molars were measured on digital dental casts at baseline (T0) and six-month follow-up (T1). Paired t-tests were used for intra-group results, and two-sample independent t-tests were used for inter-group comparisons. Results There was no significant increase in all indicators within six months in the NG group (p > 0.05). In the First group and RME group, all width indicators were significantly increased after treatment (p

Abstract 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.

Abstract Background Limited research has been conducted on the potential relationship between the dietary inflammation index (DII) and mortality, particularly in individuals with Helicobacter pylori (H. pylori) infection. This study aimed to investigate the association between the DII and H. pylori infection, as well as their respective impacts on all-cause mortality in a cohort of individuals with or without H. pylori infection. Methods Data from the 1999–2018 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 4370 participants included. Both univariable and multivariable-adjusted logistic regression analyses were employed to explore the relationship between H. pylori infection and pertinent covariates. Cox regression analysis, as well as restricted regression cubic spline analysis, were utilized to assess the association between DII and all-cause mortality among individuals with or without H. pylori infection. Results The findings demonstrated a positive correlation between DII scores and H. pylori infection, even after adjusting for potential confounding factors. Moreover, higher DII scores were significantly associated with an elevated risk of mortality exclusively in individuals with H. pylori infection, while no such association was observed in the uninfected population. Additional analysis using restricted cubic spline modeling revealed a positive linear relationship between DII scores as a continuous variable and the adjusted risk of all-cause mortality specifically in H. pylori-infected patients. Conclusion The results of this study indicated that DII was positively correlated with an increased risk of H. pylori infection and was associated with a heightened risk of all-cause mortality solely in individuals with H. pylori infection. Consequently, DII might serve as a useful tool for risk stratification in the H. pylori-infected population among U.S. adults. Further research is warranted to elucidate the underlying mechanisms and potential clinical implications of these findings.

Abstract Background Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood. Methods Differentially expressed circRNAs in GC and healthy people were screened by database. The identification of hsa_circ_000200 was verified by RNase R and sequencing, and the expression of hsa_circ_000200 was evaluated using qRT-PCR. The biological function of hsa_circ_000200 in GC was verified in vitro. Western blot, RIP, RNA fluorescence in situ hybridization, and double luciferase assay were utilized to explore the potential mechanism of hsa_circ_000200. Results Hsa_circ_000200 up-regulated in GC tissue, serum and serum exosomes. Hsa_circ_000200 in serum exosomes showed better diagnostic ability than that of tissues and serum. Combined with clinicopathological parameters, its level was related to invasion depth, TNM staging, and distal metastasis. Functionally, knockdown of hsa_circ_000200 inhibited GC cells proliferation, migration and invasion in vitro, while its overexpression played the opposite role. Importantly, exosomes with up-regulated hsa_circ_000200 promoted the proliferation and migration of co-cultured GC cells. Mechanistically, hsa_circ_000200 acted as a “ceRNA” for miR-4659a/b-3p to increase HBEGF and TGF-β/Smad expression, then promoted the development of GC. Conclusions Our findings suggest that hsa_circ_000200 promotes the progression of GC through hsa_circ_000200/miR-4659a/b-3p/HBEGF axis and affecting the expression of TGF-β/Smad. Serum exosomal hsa_circ_000200 may serve as a potential biomarker for GC.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.

As one of the most induced genes in activated macrophages, immune-responsive gene 1 (IRG1) encodes a mitochondrial metabolic enzyme catalysing the production of itaconic acid (ITA). Although ITA has an anti-inflammatory property, the underlying mechanisms are not fully understood. Here we show that ITA is a potent inhibitor of the TET-family DNA dioxygenases. ITA binds to the same site on TET2 as the co-substrate α-ketoglutarate, inhibiting TET2 catalytic activity. Lipopolysaccharide treatment, which induces Irg1 expression and ITA accumulation, inhibits Tet activity in macrophages. Transcriptome analysis reveals that TET2 is a major target of ITA in suppressing lipopolysaccharide-induced genes, including those regulated by the NF-κB and STAT signalling pathways. In vivo, ITA decreases the levels of 5-hydroxymethylcytosine, reduces lipopolysaccharide-induced acute pulmonary oedema as well as lung and liver injury, and protects mice against lethal endotoxaemia, depending on the catalytic activity of Tet2. Our study thus identifies ITA as an immune modulatory metabolite that selectively inhibits TET enzymes to dampen the inflammatory responses.