A noncanonical GTPase signaling mechanism controls exit from mitosis in budding yeast.

In the budding yeast Saccharomyces cerevisiae, exit from mitosis is coupled to spindle position to ensure successful genome partitioning between mother and daughter cell. This coupling occurs through a GTPase signaling cascade known as the mitotic exit network (MEN). The MEN senses spindle position via a Ras-like GTPase Tem1 which primarily localizes to the spindle pole bodies (SPBs, yeast equivalent of centrosomes) during anaphase. How Tem1 couples the status of spindle position to MEN activation is not fully understood. Here, we show that Tem1 does not function as a molecular switch as its nucleotide state does not change upon MEN activation. Instead, Tem1's nucleotide state regulates its SPB localization to establish a concentration difference in the cell in response to spindle position. By artificially tethering Tem1 to the SPB, we demonstrate that the essential function of Tem1GTP is to localize Tem1 to the SPB. Tem1 localization to the SPB primarily functions to generate a high effective concentration of Tem1 and MEN signaling can be initiated by concentrating Tem1 in the cytoplasm with genetically encoded multimeric nanoparticles. This localization/concentration-based GTPase signaling mechanism for Tem1 differs from the canonical Ras-like GTPase signaling paradigm and is likely relevant to other localization-based signaling scenarios.

Maternal exposure to ambient ozone and fetal conotruncal heart defects in China: A multicenter cohort study.

BACKGROUND: The relationships between maternal genetic and environmental exposure and conotruncal heart defects (CTDs) have been extensively investigated. Nevertheless, there is limited knowledge regarding the impact of ozone (O3) on the risk of CTDs. OBJECTIVE: To explore the correlation between maternal exposure to O3 and CTDs in China. METHODS: Pregnant women who underwent fetal echocardiography at Beijing Anzhen Hospital between January 2013 and December 2021 were enrolled. Their sociodemographic characteristics and lifestyle information, along with fetal data, were systematically collected. Fetal echocardiography was used to detect CTDs. Maternal exposure to ambient O3 during the embryonic period, the first trimester, the three months preceding the last menstrual period, and the perinatal period was estimated using residential addresses or hospital addresses associated with prenatal visits. The concentration of O3 was divided by quartiles, with the first quartile serving as a reference. Adjusted logistic regression models were employed to examine the associations between every 10 µg/m3 increase or quartile increase in ambient O3 exposure and CTDs. RESULTS: Among 24,278 subjects, 1069 exhibited fetuses with CTDs. Maternal exposure to ambient O3 during three pregnancy periods was associated with increased CTD risk. The adjusted odds ratio (OR) and 95% confidence interval (CI) were 1.271 (1.189-1.360) per 10 µg/m3 increase in O3 during the perinatal period. For each quartile of O3, the risk increased with increasing exposure concentration, particularly during the perinatal period (OR = 2.206 for quartile 2, 2.367 for quartile 3, and 3.378 for quartile 4, all P<0.05). CONCLUSIONS: Elevated maternal exposure to O3 during pregnancy, particularly in the perinatal period, is linked to an increased risk of fetal CTDs. Further longitudinal analyses are needed to validate these results.

Maternal Exposure to Extreme Cold Events and Risk of Congenital Heart Defects: A Large Multicenter Study in China.

Over the past decade, extreme temperature events have become more frequent and longer in duration. Previous studies on the association between extreme cold events (ECEs) and congenital heart defects (CHDs) are few and inconsistent. We conducted a national multicenter study in 1313 hospitals in 26 provinces in China and collected a total of 14 808 high CHD-risk participants from 2013 to 2021. We evaluated the ECEs experienced by each pregnant women during the embryonic period (3-8 weeks). The results indicated that ECEs experienced by pregnant women during the embryonic period were associated with the development of fetal CHD and were more strongly associated with some specific fetal CHD subtypes, such as pulmonary stenosis, pulmonary atresia, and tetralogy of Fallot. Of the CHD burden, 2.21% (95% CI: 1.43, 2.99%)-2.40% (95% CI: 1.26, 3.55%) of fetal CHD cases were attributable to ECEs during the embryonic period. Our findings emphasize the need to pay more attention to pregnant women whose embryonic period falls during the cold season to reduce cold spell detriments to newborns.

Highly selective colorimetric determination of glutathione based on sandwich-structured nanoenzymes composed of gold nanoparticle-coated molecular imprinted metal-organic frameworks.

A sandwich-structured composite nanoenzyme (NH2-MIL-101(Fe)@Au@MIP) was prepared using molecularly imprinted polymers, metal-organic frameworks, and gold nanoparticles and a highly selective glutathione (GSH) colorimetric sensor was constructed. The inner part of the composite nanoenzymes is a metal-organic framework loaded with gold nanoparticles (AuNPs), NH2-MIL-101(Fe)@Au, which has superior peroxidase-like activity compared with  NH2-MIL-101(Fe). This is due to the surface plasmon resonance effect of AuNPs. GSH can form strong Au-S bonds with AuNPs, which can significantly reduce the enzymatic activity of NH2-MIL-101(Fe)@Au, thereby changing the absorbance at 450 nm of the sensing system. The degree of change in absorbance is correlated with the concentration of GSH. In the outer part, the molecularly imprinted polymer with oxidized glutathione (GSSG) as a dummy template provided specific pores, which significantly improved the selectivity of the sensing system. The sensor showed good GSH sensing performance in the range 1 ~ 50 µM with a lower limit of detection (LOD) of 0.231 µM and good sensing performance in fetal bovine serum, indicating its high potential for clinical diagnostic applications.

Application of neural networks in prenatal diagnosis of atrioventricular septal defect.

Background: There is no relevant study on landmarks detection, one of the Convolutional Neural Network algorithms, in the field of fetal echocardiography (FE). This study aimed to explore whether automatic landmarks detection could be used in FE correctly and whether the atrial length (AL) to ventricular length (VL) ratio (AVLR) could be used to diagnose atrioventricular septal defect (AVSD) prenatally. Methods: This was an observational study. Two hundred and seventy-eight four-chamber views in end diastole, divided into the normal, AVSD, and differential diagnosis groups, were retrospectively included in this study. Seven landmarks were labeled sequentially by the experts on these images, and all images were divided into the training and test sets for normal, AVSD, and differential diagnosis groups. U-net, MA-net, and Link-net were used as landmark prediction neural networks. The accuracy of the landmark detection, AL, and VL measurements, as well as the prenatal diagnostic effectiveness of AVLR for AVSD, was compared with the expert labeled. Results: U-net, MA-net, and Link-net could detect the landmarks precisely (within the localization error of 0.09 and 0.13 on X and Y axis) and measure AL and VL accurately (the measured pixel distance error of AL and VL were 0.12 and 0.01 separately). AVLR in AVSD was greater than in other groups (P<0.0001), but the statistical difference was not obvious in the complete, partial, and transitional subgroups (P>0.05). The diagnostic effectiveness of AVLR calculated by three models, area under receiver operating characteristic curve could reach 0.992 (0.968-1.000), was consistent with the expert labeled. Conclusions: U-net, Link-net, and MA-net could detect landmarks and make the measurements accurately. AVLR calculated by three neural networks could be used to make the prenatal diagnosis of AVSD.

Genetic aetiology distribution of 398 foetuses with congenital heart disease in the prenatal setting.

AIMS: Copy number variant-sequencing (CNV-seq) and exome sequencing (ES) have been used as powerful tools in understanding the role of genetic variants in congenital heart diseases (CHDs). A few previous large cohort studies have utilized CNV-seq and ES to investigate prenatally diagnosed CHD. Here, we sought to determine the value of CNV-seq and ES for genetic evaluation of foetal CHDs. METHODS AND RESULTS: We recruited 398 pregnant women diagnosed with CHDs between 8 January 2017 and 30 November 2020. CNV-seq and ES were performed on foetal and parent samples. CHD cases were classified following the guidelines of the International Paediatric and Congenital Cardiac Code and the Tenth and Eleventh Revisions of the International Classification of Diseases. Data on aneuploids (AUP), pathogenic CNVs (pCNVs), and single nucleotide variants (SNVs) were collected and compared, following appropriate procedures. We identified genetic abnormalities in 129 (32.41%) foetuses. These abnormalities included AUP (10.80%), pCNVs (13.32%), and SNVs (8.04%). ES analysis yielded higher SNVs in cases without AUP or pCNVs. Non-isolated CHDs were associated with higher genetic abnormalities than isolated CHDs, mainly due to AUP differences between the two groups. The prevalence of genetic defects was the highest in foetuses with atrioventricular septal defects (AVSD), left ventricular outflow tract obstruction (LVOTO), and conotruncal defects (CTD). AVSD and anomalies of atrioventricular junctions and valves were associated with AUP abnormalities. CTD, anomalies of extrapericardial arterial trunks, and anomalies of the ventricular outflow tracts were the most common CHD categories diagnosed using CNVs. The most common CHDs associated with single ventricle (SV) abnormalities were heterotaxy (Hex) (14.89%), LVOTO (14.58%), and ventricular septal defect (VSD) (26.67%, 4/15). Although the ES yields were higher than CNV-seq for VSD (44.4%, 4/9), LVOTO (20%, 7/35), Hex (14.89%, 7/47), and CTD (9.1%, 11/121), its diagnostic yield did not increase for SV (6.7%, 1/15), AVSD (3.8%, 1/26), or right ventricular obstruction defects (2.6%, 1/38). The most common mutations were observed in KMT2D, CHD7, and NOTCH1. CONCLUSIONS: To our knowledge, this is the largest cohort study to investigate the incidence of SNVs using ES in foetal CHD. CNV-seq and ES identified genetic abnormalities in nearly 1/3 of foetal CHD cases. Thus, CNV-seq and ES can provide clinically relevant information for pregnancy management.

An Unguarded Tricuspid Valve Orifice Diagnosed by Autopsy.

Introduction: Fetal unguarded tricuspid valve orifice (UTVO) is characterized by a complete or partial absence of the tricuspid valvular tissue or sub-valvular apparatus and only case reports are available at present. We report a UTVO diagnosed by fetal autopsy. Case report: An 18-week fetus was diagnosed by prenatal ultrasound with tricuspid dysplasia with 'to-and-fro' flow across the right-sided heart. Fetal autopsy showed partial agenesis of tricuspid valve instead of valvular dysplasia. This supported a diagnosis of UTVO. Conclusion: Fetal autopsy can differentiate UTVO form other valve abnormalities. The 'to-and-fro' flow pattern across the right atrioventricular orifice could be used to differentiate UTVO from other valve dysplasias on echocardiography.

Genetic abnormalities in fetal congenital heart disease with aberrant right subclavian artery.

Fetal aberrant right subclavian artery (ARSA) is a relatively common sonographic finding. Congenital heart disease (CHD) is the most common structural abnormality in patients with ARSA. We aimed to assess the prevalence of genetic abnormalities, particularly sequence variants, in fetuses with CHD and ARSA. By clinical phenotyping and genomic sequencing, we retrospectively reviewed all fetuses with a prenatal diagnosis of CHD combined with ARSA at a single center. As a result, we identified 30 fetuses with ARSA combined with CHD, with conotruncal anomalies being the most common (n = 12, 40%), followed by left ventricular outflow tract obstruction (n = 6, 20%) and atrioventricular septal defects (n = 6, 20%). Overall, 18 (60%) cases had a genetic diagnosis. Copy number variation sequencing analysis identified six (20%) fetuses with aneuploidy and seven (23%) with pathogenic copy-number variants. Whole-exome sequencing (WES) analysis of the remaining 17 cases revealed diagnostic genetic variants in five (29%) cases, indicating that the diagnostic yield of WES for the entire cohort was 17% (5/30). Our findings reveal the high burden of genetic abnormalities in fetal CHD with ARSA. Single-gene disorders contribute substantially to the genetic etiology of fetal CHD with ARSA.

Role of pyroptosis in inflammation and cancer.

Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures, resulting in the release of cellular contents that can activate strong inflammatory and immune responses. Pyroptosis, an innate immune response, can be triggered by the activation of inflammasomes by various influencing factors. Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11, both of which cleave gasdermin D to release its N-terminal domain, which can bind membrane lipids and perforate the cell membrane. Here, we review the latest advancements in research on the mechanisms of pyroptosis, newly discovered influencing factors, antitumoral properties, and applications in various diseases. Moreover, this review also provides updates on potential targeted therapies for inflammation and cancers, methods for clinical prevention, and finally challenges and future directions in the field.

Breast cancer cell-derived extracellular vesicles promote CD8+ T cell exhaustion via TGF-ß type II receptor signaling.

Cancer immunotherapies have shown clinical success in various types of tumors but the patient response rate is low, particularly in breast cancer. Here we report that malignant breast cancer cells can transfer active TGF-ß type II receptor (TßRII) via tumor-derived extracellular vesicles (TEV) and thereby stimulate TGF-ß signaling in recipient cells. Up-take of extracellular vesicle-TßRII (EV-TßRII) in low-grade tumor cells initiates epithelial-to-mesenchymal transition (EMT), thus reinforcing cancer stemness and increasing metastasis in intracardial xenograft and orthotopic transplantation models. EV-TßRII delivered as cargo to CD8+ T cells induces the activation of SMAD3 which we demonstrated to associate and cooperate with TCF1 transcription factor to impose CD8+ T cell exhaustion, resulting in failure of immunotherapy. The levels of TßRII+ circulating extracellular vesicles (crEV) appears to correlate with tumor burden, metastasis and patient survival, thereby serve as a non-invasive screening tool to detect malignant breast tumor stages. Thus, our findings not only identify a possible mechanism by which breast cancer cells can promote T cell exhaustion and dampen host anti-tumor immunity, but may also identify a target for immune therapy against the most devastating breast tumors.

USP8 promotes cancer progression and extracellular vesicle-mediated CD8+ T cell exhaustion by deubiquitinating the TGF-ß receptor TßRII.

TGF-ß signaling is a key player in tumor progression and immune evasion, and is associated with poor response to cancer immunotherapies. Here, we identified ubiquitin-specific peptidase 8 (USP8) as a metastasis enhancer and a highly active deubiquitinase in aggressive breast tumors. USP8 acts both as a cancer stemness-promoting factor and an activator of the TGF-ß/SMAD signaling pathway. USP8 directly deubiquitinates and stabilizes the type II TGF-ß receptor TßRII, leading to its increased expression in the plasma membrane and in tumor-derived extracellular vesicles (TEVs). Increased USP8 activity was observed in patients resistant to neoadjuvant chemotherapies. USP8 promotes TGF-ß/SMAD-induced epithelial-mesenchymal transition (EMT), invasion, and metastasis in tumor cells. USP8 expression also enables TßRII+ circulating extracellular vesicles (crEVs) to induce T cell exhaustion and chemoimmunotherapy resistance. Pharmacological inhibition of USP8 antagonizes TGF-ß/SMAD signaling, and reduces TßRII stability and the number of TßRII+ crEVs to prevent CD8+ T cell exhaustion and to reactivate anti-tumor immunity. Our findings not only reveal a novel mechanism whereby USP8 regulates the cancer microenvironment but also demonstrate the therapeutic advantages of engineering USP8 inhibitors to simultaneously suppress metastasis and improve the efficacy of cancer immunotherapy.

Genetic and Clinical Features of Heterotaxy in a Prenatal Cohort.

Objectives: Some genetic causes of heterotaxy have been identified in a small number of heterotaxy familial cases or animal models. However, knowledge on the genetic causes of heterotaxy in the fetal population remains scarce. Here, we aimed to investigate the clinical characteristics and genetic spectrum of a fetal cohort with heterotaxy. Methods: We retrospectively investigated all fetuses with a prenatal diagnosis of heterotaxy at a single center between October 2015 and November 2020. These cases were studied using the genetic testing data acquired from a combination of copy number variation sequencing (CNV-seq) and whole-exome sequencing (WES), and their clinical phenotypes were also reviewed. Result: A total of 72 fetuses diagnosed with heterotaxy and complete clinical and genetic results were enrolled in our research. Of the 72 fetuses, 18 (25%) and 54 (75%) had left and right isomerism, respectively. Consistent with the results of a previous study, intracardiac anomalies were more severe in patients with right atrial isomerism than in those with left atrial isomerism (LAI) and mainly manifested as atrial situs inversus, bilateral right atrial appendages, abnormal pulmonary venous connection, single ventricles or single atria, and pulmonary stenosis or atresia. In 18 fetuses diagnosed with LAI, the main intracardiac anomalies were bilateral left atrial appendages. Of the 72 fetuses that underwent CNV-seq and WES, 11 (15.3%) had positive genetic results, eight had definitive pathogenic variants, and three had likely pathogenic variants. The diagnostic genetic variant rate identified using WES was 11.1% (8/72), in which primary ciliary dyskinesia (PCD)-associated gene mutations (CCDC40, CCDC114, DNAH5, DNAH11, and ARMC4) accounted for the vast majority (n = 5). Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases, although they have been verified to play roles in congenital heart disease. Conclusion: Thus, diagnostic genetic variants contributed to a substantial fraction in the etiology of fetal heterotaxy. PCD mutations accounted for approximately 6.9% of heterotaxy cases in our fetal cohort. WES was identified as an effective tool to detect genetic causes prenatally in heterotaxy patients.

Microbiota in Tumors: From Understanding to Application.

Microbes with complex functions have been found to be a potential component in tumor microenvironments. Due to their low biomass and other obstacles, intratumor microbiota is poorly understood. Mucosal sites and normal adjacent tissues are important sources of intratumor microbiota, while hematogenous spread also leads to the invasion of microbes. Intratumor microbiota affects the progression of tumors through several mechanisms, such as DNA damage, activation of oncogenic pathways, induction of immunosuppression, and metabolization of drugs. Notably, in different types of tumors, the composition and abundance of intratumor microbiota are highly heterogeneous and may play different roles in the progression of tumors. Because of the concern in this field, several techniques such as omics and immunological methods have been used to study intratumor microbiota. Here, recent progress in this field is reviewed, including the potential sources of intratumor microbiota, their functions and related mechanisms, and their heterogeneity. Techniques that can be used to study intratumor microbiota are also discussed. Moreover, research is summarized into the development of strategies that can be used in antitumor treatment and prospects for possible future research in this field.

The Multilevel Study on the Impact of High-Performance Human Resource Practices on Employees' Voice Behavior: A Moderated Mediation Model.

Based on the social identity theory, the relationship and influencing mechanism between high-performance human resource practices (HPHRPs) and employees' voice behavior were explored by constructing a moderated mediation model, and the relationship between the field of human resources and the field of organizational behavior was also established. Through 1,178 paired samples of supervisor-employee survey and multilevel linear model analysis technology, it was found that (1) HPHRPs had a positive impact on employees' voice behavior; (2) perceived insider status played a mediating role between HPHRPs and voice behavior; (3) voice efficacy played a moderating role between perceived insider status and voice behavior; and (4) voice efficacy played a mediating role in the relationship between "HPHRPs-perceived insider status-voice behavior."

Measurement of contagion spatial spread probability in public places: A case study on COVID-19.

The scale and scope of the COVID-19 epidemic have highlighted the need for timely control of viral transmission. This paper proposed a new spatial probability model of epidemic infection using an improved Wasserstein distance algorithm and Monte Carlo simulation. This method identifies the public places in which COVID-19 spreads and grows easily. The Wasserstein Distance algorithm is used to calculate the distribution similarity between COVID-19 cases and the public places. Further, we used hypothesis tests and Monte Carlo simulation to estimate the spatial spread probability of COVID-19 in different public places. We used Snow's data to test the stability and accuracy of this measurement. This verification proved that our method is reliable and robust. We applied our method to the detailed geographic data of COVID-19 cases and public places in Wuhan. We found that, rather than financial service institutions and markets, public buildings such as restaurants and hospitals in Wuhan are 95 percent more likely to be the public places of COVID-19 spread.

Expanding the phenotype associated with SMARCC2 variants: a fetus with tetralogy of Fallot.

BACKGROUND: Coffin-Siris syndrome-8 (CSS8) is a rare autosomal dominant disorder caused by variants in SMARCC2, a core subunit of the chromatin-remodeling complex BRG1-associated factor (BAF). The clinical characteristics of this disorder have not been entirely determined because of the rarity of clinical reports. The BAF complex plays a crucial role in embryogenesis and cardiac development, and pathogenic variants in genes encoding the components of the BAF complex have been associated with congenital heart disease (CHD). However, variants in SMARCC2 have not been reported in patients with CHD. CASE PRESENTATION: A 28-year-old primigravida was referred at 24 weeks gestation for prenatal echocardiography. The echocardiographic findings were consistent with a prenatal ultrasound diagnosis of tetralogy of Fallot (TOF). After detailed counseling, the couple decided to terminate the pregnancy and undergo genetic testing. A trio (fetus and the parents) whole-exome sequencing (WES) and copy number variation sequencing (CNV-seq) were performed. CNV-seq identified no chromosomal abnormalities. WES analysis revealed a pathogenic, de novo heterozygous frameshift variant in SMARCC2 (NM_003075.5: c.3561del, p.Leu1188fs). The genetic diagnosis of CSS8 was considered given the identification of the SMARCC2 pathogenic variant. CONCLUSIONS: We report the first prenatal case with the SMARCC2 variant. The presence of CHD further broadens the phenotypic spectrum of SMARCC2-related disease.

Deep eutectic solvents boosting solubilization and Se-functionalization of heteropolysaccharide: Multiple hydrogen bonds modulation.

In this study, the favorable feasibility of deep eutectic solvents (DESs) in solubilization and functionalization of natural heteropolysaccharide was validated by experiments and density functional theory calculations. This revealed that choline chloride-based DES/DMSO (dimethyl sulfoxide) binary mixed solvents possessed more and stronger hydrogen bonding sites, facilitating the balance between disruption and reconstruction of hydrogen bonds within branched heteropolysaccharide from Artemisia sphaerocephala (PAS) and achieving efficient solubilization. Further, due to the full exposure and activation of polysaccharide hydroxyls, the efficiency of DES/DMSO-mediated novel Se-functionalization was substantially enhanced compared to the conventional selenylation methods. The derivative exhibited conversion to lower molecular mass with rigid solution conformation based on co-solvent effect and predominant acidic environment influence. This study offered a framework for exploring the potential of individualized polysaccharide functionalization by modulating DES constituents to achieve multiple controllabilities in terms of conversion efficiency and derivative structure.

Case Report: Biventricular Noncompaction Cardiomyopathy With Pulmonary Stenosis and Bradycardia in a Fetus With KCNH2 Mutation.

Background: Left ventricular noncompaction (LVNC) is a rare cardiomyopathy, long QT syndrome (LQTS) is a rare ion channel disease, and simultaneous occurrence of both is even rarer. Further clinical reports and studies are needed to identify the association between LVNC and LQTS and the underlying mechanism. Methods and Results: A 26-year-old primigravida was referred at 25 weeks gestation for prenatal echocardiography due to fetal bradycardia detected during the routine ultrasound examination. The echocardiographic findings were consistent with biventricular noncompaction cardiomyopathy (BVNC) with pulmonary stenosis and suspected LQTS. After detailed counseling, the couple decided to terminate the pregnancy, and subsequent postmortem examination confirmed BVNC and pulmonary stenosis. Then, A trio (fetus and the parents) whole-exome sequencing (WES) and copy number variation sequencing (CNV-seq) were performed. CNV-seq identified no aneuploidy or pathogenic CNV. A de novo missense variant in KCNH2 (NM_000238.3:c.1847A > G,p.Tyr616Cys) was identified by WES. This KCNH2 missense mutation was classified as pathogenic according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology variant interpretation guidelines. Conclusion: We report the first prenatal case of KCNH2 mutation presenting with LVNC combined with bradycardia and second-degree 2:1 atrioventricular block. Importantly, this case reminds clinicians to systematically search ion channel gene mutations in patients with LVNC and arrhythmia.

Ferroptosis in cancer and cancer immunotherapy.

The hallmark of tumorigenesis is the successful circumvention of cell death regulation for achieving unlimited replication and immortality. Ferroptosis is a newly identified type of cell death dependent on lipid peroxidation which differs from classical programmed cell death in terms of morphology, physiology and biochemistry. The broad spectrum of injury and tumor tolerance are the main reasons for radiotherapy and chemotherapy failure. The effective rate of tumor immunotherapy as a new treatment method is less than 30%. Ferroptosis can be seen in radiotherapy, chemotherapy, and tumor immunotherapy; therefore, ferroptosis activation may be a potential strategy to overcome the drug resistance mechanism of traditional cancer treatments. In this review, the characteristics and causes of cell death by lipid peroxidation in ferroptosis are briefly described. In addition, the three metabolic regulations of ferroptosis and its crosstalk with classical signaling pathways are summarized. Collectively, these findings suggest the vital role of ferroptosis in immunotherapy based on the interaction of ferroptosis with tumor immunotherapy, chemotherapy and radiotherapy, thus, indicating the remarkable potential of ferroptosis in cancer treatment.

Fetal Heart and Descending Aorta Detection in Four-Chamber View of Fetal Echocardiography.

Automatic analysis of fetal heart and related components in fetal echocardiography can help cardiologists to reach a diagnosis for Congenital Heart Disease (CHD). Previous studies mainly focused on cardiac chamber segmentation, while few researches deal with the cardiac component detection. In this paper, we tackle the task of simultaneous detection of the fetal heart and descending aorta in four-chamber view of fetal echocardiography, which is useful to analyze some kinds of CHD, such as left/right atrial isomerism, dextroversion of heart, etc. Several CNN-based object detection methods with different backbones are thoroughly evaluated, and finally, the Hybrid Task Cascade method with HRNet is selected as the detection method. Experiments on a fetal echocardiography dataset show that the method can achieve superior performance according to common-used evaluation metrics.Clinical relevance-This can be used to help the cardiologists to estimate the position of the fetal heart and the descending aorta, which is also useful to estimate the direction of the cardiac axis and apex and analyze some kinds of CHD, such as left/right atrial isomerism, dextroversion of heart, etc.