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Triggering ferroptosis represents a promising anticancer therapeutic strategy, but the development of a selective ferroptosis inducer for cancer-specific therapy remains a great challenge. Herein, a H2S-responsive iridium(III) complex NA-Ir has been well-designed as a ferroptosis inducer. NA-Ir could selectively light up H2S-rich cancer cells, primarily localize in mitochondria, intercalate into mitochondrial DNA (mtDNA), and induce mtDNA damage, exhibiting higher anticancer activity under light irradiation. Mechanistic studies showed that NA-Ir-mediated PDT triggered lipid peroxidation and glutathione peroxidase 4 downregulation through ROS production and GSH depletion, resulting in ferroptosis through multiple pathways. Moreover, the intense mtDNA damage can activate the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway, leading to ferritinophagy and further ferroptosis. RNA-sequencing analysis showed that NA-Ir-mediated PDT mainly affects the expression of genes related to ferroptosis, autophagy, and cancer immunity. This study demonstrates the first cancer-specific example with ferroptosis and cGAS-STING activation, which provides a new strategy for multimodal synergistic therapy.

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The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems1,2. However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications3,4. Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine.

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Ionizing radiation exposure can cause damage to diverse tissues and organs, with the hematopoietic system being the most sensitive. However, limited information is available regarding the radiosensitivity of various hematopoietic cell populations in the bone marrow due to the high heterogeneity of the hematopoietic system. In this study, we observed that granulocyte-macrophage progenitors, hematopoietic stem/progenitor cells, and B cells within the bone marrow showed the highest sensitivity, exhibiting a rapid decrease in cell numbers following irradiation. Nonetheless, neutrophils, natural killer (NK) cells, T cells, and dendritic cells demonstrated a certain degree of radioresistance, with neutrophils exhibiting the most pronounced resistance. By employing single-cell transcriptome sequencing, we investigated the early responsive genes in various cell types following irradiation, revealing that distinct gene expression profiles emerged between radiosensitive and radioresistant cells. In B cells, radiation exposure led to a specific upregulation of genes associated with mitochondrial respiratory chain complexes, suggesting a connection between these complexes and cell radiosensitivity. In neutrophils, radiation exposure resulted in fewer gene alterations, indicating their potential for distinct mechanisms in radiation resistance. Collectively, this study provides insights into the molecular mechanism for the heterogeneity of radiosensitivity among the various bone marrow hematopoietic cell populations.

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Background: Anhedonia is a deficit of dynamic reward process, and a large proportion of schizophrenia patients continue to experience anhedonia even during the stable phase. However, few studies have examined the multiple aspects of performance in reward processing in patients with stable schizophrenia and evidence suggests that physical and cognitive effort may involve different neural mechanisms. Methods: Parallel measures of effort-based expenditure for reward tasks (EEfRT) and self-report questionnaires of pleasure were applied in 61 patients with stable schizophrenia (SSZ) and 46 healthy controls (HCs), and percentages of hard task choices (HTC%) were used to assess motivation in reward processing. Negative symptoms, neurocognitive and social function were evaluated in SSZ patients, and associations with performance in reward tasks were explored. Results: SSZ patients reported more severe consummatory and anticipatory anhedonia and social anhedonia. HTC% in reward tasks of SSZ patients were significantly lower than that of HCs, especially in cognitive-effort tasks. HTC% in cognitive tasks were correlated with motivation and pleasure dimension of negative symptoms, whereas HTC% in physical tasks were associated with expression dimension. Anticipatory anhedonia and negative symptoms were correlated with Personal and Social Performance Scale (PSP) scores. Conclusion: Patients with stable schizophrenia have social anhedonia, physically consummatory and anticipatory anhedonia and reduced reward motivation. They are less willing to make cognitive effort than physical effort for reward. The different associations of physical and cognitive effort with negative symptoms indicate physical and cognitive effort may represent disparate neuropsychological processes. Anticipatory anhedonia is closely related to social functioning.

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In the push to achieve net-zero emissions by 2050, nuclear power will play an essential role alongside renewable wind and solar power, and correspondingly global interest and investment in this well-established technology is accelerating. The uranium present in seawater could support nuclear power generation for centuries, but traditional adsorptive separation strategies have proven ineffective for the selective extraction of uranium from this vast resource. Here, we report the synthesis of nanowires of a triazine-linked two-dimensional covalent organic framework via a solvent modulation approach, which can be used to access nanowire external diameters ranging from 50 to 200 nm. The 100 nm nanowires are exceptionally promising for the capture of uranium(VI) via photocatalytic reduction. Under simulated sunlight and without the use of sacrificial agents, the nanowires achieve a uranium uptake of 10.9 g/g from a 100 ppm uranyl(VI) solution, which is the highest reported to date among materials studied for photo and electrocatalytic uranium capture. Significantly, these nanowires exhibit a uranium adsorption capacity of 34.5 mg/g after exposure to seawater under irradiation for 42 days, a record among all materials reported to date for uranium capture.

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BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

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Background: LEOPARD syndrome (LS) is a rare genetic disorder presenting various clinical manifestations from childhood, complicating its diagnosis. In this study, we aim to refine the imaging presentation of LS and emphasize the importance of multimodality imaging in enhancing diagnostic accuracy and preventing serious cardiovascular events. Case: A 41-year-old woman was admitted to hospital with a suspected apical tumor detected by a transthoracic echocardiogram (TTE), which was later identified as apical myocardial hypertrophy through cardiac magnetic resonance imaging (CMR). She had abnormal electrocardiograms from the age of 2 years and freckles around the age of 4 years. In recent years, she has been experiencing exertional dyspnea. Supplemental coronary computer tomography angiography (CCTA) revealed diffuse coronary dilatation. Both multimodality imaging and clinical manifestations led to a suspicion of LS, which was confirmed by subsequent genetic testing. The patient declined further treatment. A 3-month follow-up CMR showed no significant change in the lesion. Conclusion: This report elucidates the diagnostic transition from an initial suspicion of an apical tumor by TTE to a definitive diagnosis of left ventricular apical hypertrophy by CMR in a 41-year-old woman with LS. It underscores the value of multimodality imaging (TTE, CCTA, CMR) in unraveling unusual cardiac manifestations in rare genetic disorders such as LS.

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BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a rare but severe disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 infection. It develops in adults with inflammation of different organs including the gastrointestinal tract, heart, kidneys, skin and hematopoietic system. CASE SUMMARY: We present a 58-year-old Chinese man diagnosed with MIS-A. His chief complaints were fever, generalized fatigue and anorexia, accompanied with rashes on his back. Further examination showed cardiac, renal and liver injury. He had melena and gastroscopy indicated esophageal ulcer and severe esophagitis. Repeated blood and sputum culture did not show growth of bacteria or fungi. Antibiotic treatment was stopped due to unsatisfactory performance. His condition improved after prednisone and other supportive treatment. CONCLUSION: Gastrointestinal involvement in MIS-A is not uncommon. Intestinal involvement predominates, and esophageal involvement is rarely reported. Esophageal ulcer with bleeding could also be a manifestation of MIS-A.

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Broadband spectrum detectors exhibit great promise in fields such as multispectral imaging and optical communications. Despite significant progress, challenges like materials instability in such devices, complex manufacturing process, and high cost still hinder their further application. Here, we present a method that achieves broadband spectral detection by impurity-level in SrSnO3. We report over 500 mA/W photoresponsivity at 275 nm (ultraviolet C solar-bind) and 367 nm (ultraviolet A) and ∼60 mA/W photoresponsivity at 532 and 700 nm (visible) with a voltage bias of -5 V. Further transport and photoluminescence results reveal a new phase transition at 88 K, which would significantly affect the impurity level of the La-doped SrSnO3 film, indicating that the broadband response attributes to the impurity levels and mutual interactions. Additionally, the photodetector demonstrates excellent robustness and stability under repeated tests and prolonged exposure in air. These findings show the potential of SrSnO3 as a material for photodetectors and propose a method to achieve broadband spectrum detection, creating new possibility for the development of single-phase, low-cost, simple structure, and high-efficiency photodetectors.

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With the popularization of electronic products, visual fatigue is inevitably frequent. The causes of visual fatigue are varied, but from the perspective of physiological mechanisms, it is mainly closely related to retinal function or structural damage, especially the light source from various mobile devices and office equipments nowadays, which induces oxidative stress damage in the retina and exacerbates the degree of visual fatigue, resulting in the inability to use the eyes for a long period of time, pain in the eyes and periorbital area, blurred vision, dry eyes, tearing, and other discomforts. Food ingredients derived from natural plants have greater application in relieving visual fatigue. Therefore, this paper presents a detailed compilation of six plants that are widely used for their visual fatigue-relieving function, in the hope of providing more raw material choices for the development of products with visual fatigue-relieving functions in the future.

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In the aquaculture system of ornamental fish, the interaction between bacterial microbiota and ciliate protozoa can prevent or promote disease outbreaks, and different physicochemical conditions will affect the relationships between them. We investigated the interaction between bacterial microbiota and the parasite Tetrahymena pyriformis when infecting Poecilia reticulata (guppy) under different physicochemical conditions. The abundance of T. pyriformis in water, the relative abundance of bacterial species, and histopathological observation were studied or monitored using environmental DNA (eDNA) extraction technology, the qPCR method, and 16s rRNA sequencing, respectively. The morphological identification and phylogenetic analysis of T. pyriformis were carried out. The infected guppy tissue was also stained by the hematoxylin and eosin methods. The results showed: (1) the bacterial communities of water samples were mainly composed of species assigned to Proteobacteria and Bacteroidetes, and Tabrizicola and Puniceicoccaceae were positively correlated with fish mortality, T. pyriformis abundance, and temperature. (2) Arcicella and Methyloversatilis universalis with different correlations between ciliates appeared in different treatment groups, the result of which proved that environmental factors affected the interaction between bacteria and T. pyriformis. (3) Lower temperatures and a higher pH were more beneficial for preventing disease outbreaks.

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Ovarian function suppression (OFS) benefits young women with hormone receptor (HR)-positive breast cancer but they are at risk for ovarian function breakthrough. We assessed endocrine effects of gonadotropin-releasing hormone agonist (GnRHa) treatment in a prospective cohort of patients aged ≤ 40 years with HR-positive breast cancer. Plasma estradiol (E2), estrone, and follicule-stimulating hormone (FSH) levels were measured from blood samples drawn 1 and 4 years after diagnosis. Patient characteristics, invasive breast cancer-free survival (iBCFS), and overall survival (OS) were compared between those with and without E2 > 2.72 pg/mL during GnRHa treatment. Among eligible patients, 54.7% (46/84) and 60% (15/25) had E2 > 2.72 pg/mL at 1 and 4 years, respectively. Factors associated with E2 > 2.72 pg/mL at 1 year were no prior chemotherapy (P = 0.045) and tamoxifen use (P = 0.009). After a median follow-up of 7 years, among patients with stage I-III breast cancer (N = 74), iBCFS events were seen in 6 (8.1%) with E2 > 2.72 pg/mL and 5 (6.8%) with E2 ≤ 2.72 pg/mL (P = 0.893). Among patients with de novo metastatic breast cancer (N = 12), 6 (50%) with E2 > 2.72 pg/mL and 3 (25%) with E2 ≤ 2.72 pg/mL died during follow-up (P = 0.052). Larger studies exploring the clinical implications of incomplete E2 suppression by GnRHa are needed to ensure optimal OFS treatment strategies are being employed for this population.

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OBJECTIVES: To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC's etiology and further support the development of therapeutic strategies. METHODS: A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. RESULTS: UC patients demonstrated significantly higher native T1 (p < 0.001 for all) and T2 (p < 0.002 for all) values compared with the other three groups. UC patients revealed higher left atrial reservoir strain rate (p < 0.001 for all) and left atrial conduit strain rate (p < 0.001 for all) absolute values as compared with HTN and HCM patients. A significant correlation between T1 and T2 values in UC patients (r = 0.511, p < 0.001) was found. The combination of T1 values and strain parameters was the best discriminator between UC and HTN patients (AUC = 0.872, 95% CI: 0.801-0.943) and between UC and HCM patients (AUC = 0.840, 95% CI: 0.746-0.934). CONCLUSION: UC reveals distinguishing tissue characteristics as evidenced by T1 and T2 mapping, as well as distinguishing functional strain parameters as compared with other hypertrophic phenotypes such as HTN and HCM. CRITICAL RELEVANCE STATEMENT: The use of CMR imaging in UC patients offers incremental information to elucidate its complex etiology, contributing to ongoing discourse on effective treatment pathways. KEY POINTS: This study investigated uremic, hypertensive, and hypertrophic cardiomyopathies using cardiac MRI. UC patients have higher T1 and T2 values and better preserved cardiac function. Combined strain and T1 values distinguish UC from other cardiomyopathies.

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Lung squamous cell carcinoma (LUSC) is one of the most common malignant tumors of the respiratory. Pyroptosis plays an essential role in cancer, but there is limited research investigating pyroptosis in LUSC. In this study, pyroptosis-related genes were observed to have extensive multiomics alterations in LUSC through analysis of the TCGA database. Utilizing machine learning for selection and verifying expression levels, GSDMC was chosen as the critical gene for further experiments. Our research found that GSDMC is overexpressed in LUSC tissues and cells, and is associated with poor prognosis. Knockdown of GSDMC in LUSC inhibits cell proliferation, invasion, metastasis, chemotherapeutic sensitivity, and reduced tumor formation in nude mice, accompanied by downregulation of proliferative and EMT-related protein expression. However, these effects were counteracted in cells where GSDMC is overexpressed. Mechanistically, the oncogenic role of GSDMC is primarily achieved through the activation of the AKT/mTOR pathway, and this effect can be significantly reversed by rapamycin. Finally, SMAD4's interaction with the promoter region of GSDMC results in the suppression of GSDMC expression. In summary, our study through bioinformatics and experimental approaches not only proves that SMAD4 regulates the protumorigenic role of GSDMC through transcriptional targeting, but also indicates the possibility of developing the SMAD4/GSDMC/AKT/mTOR signaling axis as a potential biomarker and treatment target for LUSC.

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As a common heavy metal contaminant, Cd2+ has adverse effects on food safety and consumer health. It is very important for human health to realize highly sensitive Cd2+ detection methods. The self-powered sensing system based on enzyme biofuel cells (EBFCs) does not need an external power supply, which can simplify the experimental equipment and has great application value in portable detection. Thus, the biosensor is innovatively integrated into the screen-printed electrode to construct a new type of portable sensor suitable for on-site and real-time Cd2+ detection. Hybridization chain reaction (HCR) combined with the Cd2+-dependent deoxyribose (DNAzyme) signal amplification strategy is used to enhance the detection sensitivity while specifically recognizing the Cd2+. Moreover, the self-powered sensor combines with smartphones to realize quantitative Cd2+ detection without other instruments and has the characteristic of Effectively improving the hazard detection technology is essential to ensure food safety. Portability, simplicity, and speed are suitable for real-time Cd2+ detection in the field. The dual mechanism and three quantitative modes combining colorimetric and two electrical signals output modes are adopted to realize the visualization and accurate detection. A series of research results confirm that this strategy is of great significance to strengthen the development of intelligent Cd2+ technology, expand the application of self-powered sensing technology, and improve the safety detection system.

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Deep learning models provide a more powerful method for accurate and stable prediction of water quality in rivers, which is crucial for the intelligent management and control of the water environment. To increase the accuracy of predicting the water quality parameters and learn more about the impact of complex spatial information based on deep learning models, this study proposes two ensemble models TNX (with temporal attention) and STNX (with spatio-temporal attention) based on seasonal and trend decomposition (STL) method to predict water quality using geo-sensory time series data. Dissolved oxygen, total phosphorus, and ammonia nitrogen were predicted in short-step (1 h, and 2 h) and long-step (12 h, and 24 h) with seven water quality monitoring sites in a river. The ensemble model TNX improved the performance by 2.1%-6.1% and 4.3%-22.0% relative to the best baseline deep learning model for the short-step and long-step water quality prediction, and it can capture the variation pattern of water quality parameters by only predicting the trend component of raw data after STL decomposition. The STNX model, with spatio-temporal attention, obtained 0.5%-2.4% and 2.3%-5.7% higher performance compared to the TNX model for the short-step and long-step water quality prediction, and such improvement was more effective in mitigating the prediction shift patterns of long-step prediction. Moreover, the model interpretation results consistently demonstrated positive relationship patterns across all monitoring sites. However, the significance of seven specific monitoring sites diminished as the distance between the predicted and input monitoring sites increased. This study provides an ensemble modeling approach based on STL decomposition for improving short-step and long-step prediction of river water quality parameter, and understands the impact of complex spatial information on deep learning model.

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Due to its emulsifying and thickening properties, konjac glucomannan (KGM) is widely used in the food, medicine, and materials industries. Nevertheless, its high viscosity and significant water absorption limit its application range. Therefore, electron beam (e-beam) irradiation pretreatment was carried out to improve the deacetylation efficiency of KGM, and the physicochemical and gel properties of KGM were investigated. The results show that e-beam irradiation and deacetylation decrease the water absorption, solubility, transparency, molecular weight, and viscosity of KGM. Conversely, the moisture content, thermal stability, and water-binding capacity increase. FTIR and X-ray diffraction analysis revealed no significant changes in the chemical and crystalline structure of KGM before and after modification. However, modification weakens the intermolecular interaction of KGM hydrosols, which affects their rheology. Furthermore, deacetylation improves the mechanical properties and water retention capacity of KGM gels. Overall, the e-beam irradiation pretreatment provides a method to increase the efficiency of KGM deacetylation and improve the physical and chemical properties of KGM, thus expanding its potential applications in the food and chemical industries, among others.

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Hyperuricemia (HUA) may lead to myocardial cell damage, thereby promoting the occurrence and adverse outcomes of heart diseases. In this review, we discuss the latest clinical research progress, and explore the impact of HUA on myocardial damage-related diseases such as myocardial infarction, arrhythmias, and heart failure. We also combined recent findings from basic research to analyze potential mechanisms linking HUA with myocardial injury. In different pathological models (such as direct action of high uric acid on myocardial cells or combined with myocardial ischemia-reperfusion model), HUA may cause damage by activating the NOD-like receptor protein 3 inflammasome-induced inflammatory response, interfering with cardiac cell energy metabolism, affecting antioxidant defense systems, and stimulating reactive oxygen species production to enhance the oxidative stress response, ultimately resulting in decreased cardiac function. Additionally, we discuss the impact of lowering uric acid intervention therapy and potential safety issues that may arise. However, as the mechanism underlying HUA-induced myocardial injury is poorly defined, further research is warranted to aid in the development novel therapeutic strategies for HUA-related cardiovascular diseases.

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BACKGROUND: Despite the advent of combination antiretroviral therapy, people living with human immunodeficiency virus (PLWH) are at an increased risk for cardiac disease. PURPOSE: To explore the presence and extent of diastolic atrial and left ventricular dysfunction in PLWH using cardiac MRI in correlation with clinical markers of disease activity. STUDY TYPE: Prospective. POPULATION: A total of 163 participants comprising 101 HIV-infected individuals (age: 52 years [42-62 years]; 92% male) and 62 age- and sex-matched healthy volunteers (age: 51 years [30-72 years]; 85% male). FIELD STRENGTH/SEQUENCE: 3.0 T, cardiac MRI including balanced steady-state free precession (SSFP) for the short-axis, two-, three-, and four-chamber views were performed. ASSESSMENT: Assessment of cardiac function and strain analysis were accomplished by CVI42 software. Blood samples for CD4+ T cells and cardiac risk factors were also collected before MRI. STATISTICAL TESTS: Independent t tests, Mann-Whitney U test, Pearson's correlation analysis, and multivariate linear analyses (significance level: P < 0.05). RESULTS: PLWH had a significantly larger left atrial volume maximum index (LAVImax: 32.6 ± 8.7 vs. 28.7 ± 8.1 mL/m2), minimum (LAVImin: 14.8 ± 5.5 vs. 11.5 ± 5.4 mL/m2,), and prior to atrial contraction (LAVIpre-a: 23.4 ± 6.7 vs. 19.7 ± 7.2 mL/m2) as compared to healthy volunteers. The LA reservoir (LAtEF: 55.0 ± 10.2 vs. 61.4 ± 10.4; Sls: 29.0 ± 8.1 vs. 33.8 ± 11.8), conduit (LApEF: 28.4 ± 8.2 vs. 32.3 ± 11.3, P = 0.01; Sle: 16.3 ± 6.5 vs. 18.9 ± 8.2), and booster pump function (LAaEF: 37.4 ± 12.4 vs. 42.7 ± 13.1, P = 0.01, Sla: 12.7 ± 5.1 vs. 14.9 ± 5.7) were all significant impaired in PLWH. Global circumferential left ventricular diastolic strain rate (LVGCS-d) was significantly lower in the HIV patients. Multivariate analysis results showed that Nadir CD4+ T cells had a significant adverse association with LVGCS-d (ß = 0.51). CONCLUSION: LA structure abnormalities and LV diastolic dysfunction were manifested in PLWH, with Nadir CD4+ T cell counts potentially serving as a risk factor for early cardiac diastolic dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.