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Purpose: We aimed to evaluate the imaging features of breast lymphoma using magnetic resonance imaging (MRI). Methods: This retrospective study consisted of seven patients with pathologically confirmed breast lymphoma. The breast lymphomas were primary in six patients and secondary in one patient. All patients underwent preoperative dynamic contrast-enhanced MRI and one underwent additional diffusion-weighted imaging (DWI) with a b value of 600 s/mm2. Morphologic characteristics, enhancement features, and apparent diffusion coefficient (ADC) values were reviewed. Results: On MRI, three patients presented with a single mass, one with two masses, two with multiple masses, and one with a single mass and a contralateral focal enhancement. The MRI features of the eight biopsied masses in seven patients were analyzed. On MRI, the margins were irregular in six masses (75%) and spiculated in two (25%). Seven masses (87.5%) displayed homogeneous internal enhancement, while one (12.5%) showed rim enhancement. Seven masses (87.5%) showed a washout pattern and one (12.5%) showed a plateau pattern. The penetrating vessel sign was found in two masses (25%). One patient with two masses underwent DWI. Both masses showed hyperintense signal on DWI with ADC values of 0.867×10-3 mm2/s and 0.732×10-3 mm2/s, respectively. Conclusion: Breast lymphoma commonly presents as a homogeneously enhancing mass with irregular margins and displays a washout curve pattern on dynamic MRI. A low ADC value may also indicate a possible diagnosis of breast lymphoma. [ABSTRACT FROM AUTHOR]

Objectives: To build an artificial intelligence (AI) system to classify benign and malignant non-mass enhancement (NME) lesions using maximum intensity projection (MIP) of early post-contrast subtracted breast MR images. Methods: This retrospective study collected 965 pure NME lesions (539 benign and 426 malignant) confirmed by histopathology or follow-up in 903 women. The 754 NME lesions acquired by one MR scanner were randomly split into the training set, validation set, and test set A (482/121/151 lesions). The 211 NME lesions acquired by another MR scanner were used as test set B. The AI system was developed using ResNet-50 with the axial and sagittal MIP images. One senior and one junior radiologist reviewed the MIP images of each case independently and rated its Breast Imaging Reporting and Data System category. The performance of the AI system and the radiologists was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The AI system yielded AUCs of 0.859 and 0.816 in the test sets A and B, respectively. The AI system achieved comparable performance as the senior radiologist (p = 0.558, p = 0.041) and outperformed the junior radiologist (p < 0.001, p = 0.009) in both test sets A and B. After AI assistance, the AUC of the junior radiologist increased from 0.740 to 0.862 in test set A (p < 0.001) and from 0.732 to 0.843 in test set B (p < 0.001). Conclusion: Our MIP-based AI system yielded good applicability in classifying NME lesions in breast MRI and can assist the junior radiologist achieve better performance. Key Points: • Our MIP-based AI system yielded good applicability in the dataset both from the same and a different MR scanner in predicting malignant NME lesions. • The AI system achieved comparable diagnostic performance with the senior radiologist and outperformed the junior radiologist. • This AI system can assist the junior radiologist achieve better performance in the classification of NME lesions in MRI. [ABSTRACT FROM AUTHOR]

Background: Benign breast papilloma is currently managed with conservative management with close observation. In contrast, papilloma with high-risk or malignant lesions warrants surgical excision. The purpose of our study was to investigate magnetic resonance imaging (MRI) features of breast papilloma and to identify imaging diagnostic indicators for papilloma with high-risk or malignant lesions. Methods: MRI features of 175 surgically confirmed papillomas on 158 patients were retrospectively reviewed. The 175 cases included 132 cases of benign papilloma and 43 cases of papilloma with high-risk or malignant lesions. The MRI features of these lesions were classified into three types: mass, non-mass enhancement (NME), and occult lesion. The occult lesion was defined as the presence of only ductal dilation without any enhanced lesions on MRI. For a mass lesion, the mixed mass-NME lesion was considered if linear, segmental or regional enhanced lesion was found adjacent to the mass. Clinical and MRI features were compared by univariate and multivariate analysis between the benign papilloma and the papilloma with high-risk or malignant lesions. Results: Multivariate logistic regression analysis demonstrated that clinical characteristics including being or older than 50 years (odds ratio [OR] = 4.506), having bloody nipple discharge (OR = 4.499), and concurrent breast cancer (OR = 5.083) were significant indicators for papilloma with high-risk or malignant lesions. On MRI, most papillomas presented as mass (n = 135, 77.1%), and fewer as NME (n = 37, 21.1%) and occult lesion (n = 3, 1.7%). For the mass lesion, the logistic regression analysis demonstrated that a mass size exceeding 10 mm (OR = 2.956) and mixed mass-NME lesion (OR = 4.143) were independent risk indicators for a papilloma with high-risk or malignant lesions. For the NME lesion, the segmental or regional distribution was more commonly observed in the papilloma with high-risk or malignant lesions (61.5%) than the benign papilloma (12.5%) (P = 0.006). All the cases of occult lesions were benign papillomas. Conclusions: MRI features including a mass size exceeding 10 mm, mixed mass-NME lesion, and NMEs with segmental or regional distribution indicate a papilloma with high-risk or malignant lesions. [ABSTRACT FROM AUTHOR]

The effect of a high-fat diet (HFD) on mood is a widely debated topic, with the underlying mechanisms being poorly understood. This study explores the anxiolytic effects of a four-week HFD in C57BL/6 mice. Five-week-old mice were exposed to either an HFD (60% calories from fat) or standard chow diet (CD) for four weeks, followed by cannula implantation, virus infusion, behavioral tests, and biochemical assays. Results revealed that four weeks of an HFD induced anxiolytic-like behaviors and increased the protein levels of mature brain-derived neurotrophic factor (mBDNF) and phosphorylated tyrosine kinase receptor B (p-TrkB) in the medial prefrontal cortex (mPFC). Administration of a BDNF-neutralizing antibody to the mPFC reversed HFD-induced anxiolytic-like behaviors. Elevated BDNF levels were observed in both neurons and astrocytes in the mPFC of HFD mice. Additionally, these mice exhibited a higher number of dendritic spines in the mPFC, as well as upregulation of postsynaptic density protein 95 (PSD95). Furthermore, mRNA levels of the N6-methyladenosine (m6A) demethylase, fat mass and obesity-associated protein (FTO), and the hydrolase matrix metalloproteinase-9 (MMP9), also increased in the mPFC. These findings suggest that an HFD may induce FTO and MMP9, which could potentially regulate BDNF processing, contributing to anxiolytic-like behaviors. This study proposes potential molecular mechanisms that may underlie HFD-induced anxiolytic behaviors. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Despite abundant data on that many COVID-19 patients also displayed kidney disease, there is limited information available about the recovery of kidney disease after discharge.Methods: Retrospective and prospective cohort study to patients with new-onset kidney disease during the COVID-19 hospitalization, admitted between January 28 to February 26, 2020. The median follow-up was 4 months after discharge. The follow-up patients were divided into the recovery group and non-recovery group. Descriptive statistics and between-groups comparison were used.Results: In total, 143 discharged patients with new-onset kidney disease during the COVID-19 hospitalization were included. Patients had a median age was 64 (IQR, 51-70) years, and 59.4% of patients were men. During 4-months median follow-up, 91% (130 of 143) patients recovered from kidney disease, and 9% (13 of 143) patients haven't recovered. The median age of patients in the non-recovery group was 72 years, which was significantly higher than the median age of 62 years in the recovery group. Discharge serum creatinine was significantly higher in the non-recovery group than in the recovery group.Conclusions: Most of the new-onset kidney diseases during hospitalization of COVID-19 patients recovered 4 months after discharge. We recommend that COVID-19 patients with new-onset kidney disease be followed after discharge to assess kidney recovery, especially elderly patients or patients with high discharge creatinine. [ABSTRACT FROM AUTHOR]

With only limited clinical patient benefit, focusing on new immune checkpoint pathways could be an important complement to current immune checkpoint drugs. In addition, not only does T cell-mediated adaptive immunity play an important role, but also macrophage-mediated innate immunity, due to its abundant presence in solid tumors. Here, we developed an engineered M1-like macrophage exosome, OX40L M1-exos. OX40L M1-exos can activate the adaptive immunity by activating the OX40/OX40L pathway and can reprogram M2-like tumor-associated macrophages into M1-like macrophages, thereby restoring and enhancing macrophage-mediated innate immunity. Our OX40L M1-exos achieved an effective synergistic effect of innate and adaptive immunity and achieved a potent therapeutic effect in a mouse breast cancer model, effectively inhibiting tumor growth and metastasis. These results suggest that OX40L M1-exos are an attractive therapeutic strategy and may be an important complement to current cancer immunotherapies. [Display omitted] [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) often leads to high rates of disability and mortality worldwide with secondary damage due to neuroinflammation. Identification of potential therapeutic targets via the novel circular RNAs (circRNAs) would advance the field and provide a better treatment option for neuroinflammation after IS. Gene Ontology Term Enrichment (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to identify differentially expressed genes/miRNAs/circRNAs in the genome-wide RNA-seq profiles of ischemic mice. Meanwhile, relevant circRNAs were screened by differential expression analysis and coexpression RNA regulation network analysis. To explore the function of circ_22232 (Specc1l), we generated circ_22232 knockdown mice and applied middle cerebral artery occlusion (MCAO) to study IS. Cytokine levels were detected by enzyme-linked immunosorbent assay. Morphological changes were observed with immunohistochemical staining and hematoxylin-eosin staining. The circ_22232/miR-847-3p/Bmp1 axis was found to be highly correlated with neutrophil-associated neuroinflammation in cerebral tissue of mice. Immunohistochemical showed a progressive increase in the proportion of neutrophils after IS. In in vivo experiments, the circ_22232 knockdown alleviated cerebral injury by reducing the activation of neutrophils and inflammatory cytokine production. This suggests that circ_22232 is associated with inflammation, which may serve as a potential therapeutic target for IS. [ABSTRACT FROM AUTHOR]

Liposarcoma (LPS) is a rare soft tissue sarcoma that develops from the differentiation of fat cells, typically occurring in the lower extremities and retroperitoneal space. Depending on its histological morphology and molecular changes, LPS can be divided into various subtypes, each exhibiting distinct biological behaviors. During treatment, especially for LPS arising in the retroperitoneum, the extent and quality of the initial surgery are critically important. Treatment strategies must be tailored to the specific type of LPS. Over the past few decades, the treatment of LPS has undergone numerous advancements, with new therapeutic approaches such as targeted drugs and immunotherapies continually emerging. This paper reviews the biological characteristics, molecular alterations, as well as surgical and pharmacological treatments of various LPS subtypes, with the aim of enhancing clinicians' understanding and emphasizing the importance of individualized precision therapy. With a deeper understanding of the biological characteristics and molecular alterations of LPS, future treatment trends are likely to focus more on developing personalized treatment plans to better address the various types of LPS. [Display omitted] • Due to the heterogeneity of liposarcoma, the available treatment options are limited. • Expanding the scope of surgery with the aim of achieving radical cure is gradually becoming a trend in the surgical treatment of liposarcoma. • Combination drug therapy can enhance efficacy, but potential drug toxicity should also be noted. • A multidisciplinary diagnostic and therapeutic approach holds great potential for the treatment of liposarcoma. [ABSTRACT FROM AUTHOR]

Low-grade glioma (LGG) has an extremely poor prognosis, and the mechanism leading to malignant development has not been determined. The aim of our study was to clarify the function and mechanism of anoikis and TIMP1 in the malignant progression of LGG. We screened 7 anoikis-related genes from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to construct a prognostic-predicting model. The study assessed the clinical prognosis, pathological characteristics, and immune cell infiltration in both high- and low-risk groups. Additionally, the potential modulatory effects of TIMP1 on proliferation, migration, and anoikis in LGG were investigated both in vivo and in vitro. In this study, we identified seven critical genes, namely, PTGS2, CCND1, TIMP1, PDK4, LGALS3, CDKN1A, and CDKN2A. Kaplan‒Meier (K‒M) curves demonstrated a significant correlation between clinical features and overall survival (OS), and single-cell analysis and mutation examination emphasized the heterogeneity and pivotal role of hub gene expression imbalances in LGG development. Immune cell infiltration and microenvironment analysis further elucidated the relationships between key genes and immune cells. In addition, TIMP1 promoted the malignant progression of LGG in both in vitro and in vivo models. This study confirmed that TIMP1 promoted the malignant progression of LGG by inhibiting anoikis, providing insights into LGG pathogenesis and potential therapeutic targets. • Anoikis regulates tumor invasion. • Macrophages play a dual role in tumor progression. • TIMP1 is a therapeutic target for LGG. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the value of full-field digital mammography-based deep learning (DL) in predicting malignancy of Breast Imaging Reporting and Data System (BI-RADS) 4 microcalcifications. Methods: A total of 384 patients with 414 pathologically confirmed microcalcifications (221 malignant and 193 benign) were randomly allocated into the training, validation, and testing datasets (272/71/71 lesions) in this retrospective study. A combined DL model was developed incorporating mammography and clinical variables. Model performance was evaluated by using areas under the receiver operating characteristic curve (AUC) and compared with the clinical model, stand-alone DL image model, and BI-RADS approach. The predictive performance for malignancy was also compared between the combined model and human readers (2 juniors and 2 seniors). Results: The combined DL model demonstrated favorable AUC, sensitivity, and specificity of 0.910, 85.3%, and 91.9% in predicting BI-RADS 4 malignant microcalcifications in the testing dataset, which outperformed the clinical model, DL image model, and BI-RADS with AUCs of 0.799, 0.841, and 0.804, respectively. The combined model achieved non-inferior performance as senior radiologists (p = 0.860, p = 0.800) and outperformed junior radiologists (p = 0.155, p = 0.029). The diagnostic performance of two junior radiologists was improved after artificial intelligence assistance with AUCs increased to 0.854 and 0.901 from 0.816 (p = 0.556) and 0.773 (p = 0.046), while the interobserver agreement was improved with a kappa value increased to 0.843 from 0.331. Conclusions: The combined deep learning model can improve the malignancy prediction of BI-RADS 4 microcalcifications in screening mammography and assist junior radiologists to achieve better performance, which can facilitate clinical decision-making. Key Points: • The combined deep learning model demonstrated high diagnostic power, sensitivity, and specificity for predicting malignant BI-RADS 4 mammographic microcalcifications. • The combined model achieved similar performance with senior breast radiologists, while it outperformed junior breast radiologists. • Deep learning could improve the diagnostic performance of junior radiologists and facilitate clinical decision-making. [ABSTRACT FROM AUTHOR]

[Display omitted] • A simple, efficient and sensitive fluorescent biosensor for Ag+ detection. • The specificity is based on the strong, particular binding interaction of C-Ag+-C. • Excellent performance of sensitivity using HCR as amplification method. • The limited of detection of Ag+ is down to 0.69 pM. Ag is widely distributed in nature and it is used in almost all areas of human life. However, due to the widespread use of Ag materials, Ag+ pollution seriously threatens the human health and environment. The traditional detection methods for Ag+ suffer from disadvantages including high operational cost, complicated operating unit and instrument, and high requirements for professionals. Thus, in this study, a new type of Ag+ detection biosensor based on the hybridization signal amplification was designed to overcome these problems. Combining cytosine-Ag+-cytosine mismatch structure with the hybridization chain reaction, this biosensor converted the conventional detection signal into the nucleic acid amplification signal, which realized efficient, rapid, sensitive, and specific detection of Ag+. The limit-of-detection of this sensor reached 0.69 pM, which is much less than the maximum concentration (0.1 mg L−1, 927 nM) suggested for drinking water by the World Health Organization, and the maximum concentration (0.05 mg L−1, 464 nM) suggested by the United States Environmental Protection Agency. This method provides a promising new platform for detecting Ag+ concentrations at ultralow levels. [ABSTRACT FROM AUTHOR]

Abstract: In this investigation, we report the synthesis of gallium nitride (GaN) nanoparticles from ammonium-carbonato-dihydroxo-gallate (NH4[Ga(OH)2CO3]) in the flow of NH3 gas in a temperature range of 500–900°C. The GaN nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR). The FTIR and XPS revealed that the conversion of NH4[Ga(OH)2CO3] to GaN under a flow of ammonia proceeds stepwise via amorphous gallium oxynitrides (GaO x N y ) intermediates. Nanosized GaN particles with an average diameter of approximately 20–40nm were obtained. The results obtained demonstrate that the large-quantity nanosized GaN particles can be synthesized from NH4[Ga(OH)2CO3] powders. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the value of MRI radiomics based on T2-weighted (T2W) images in predicting preoperative synchronous distant metastasis (SDM) in patients with rectal cancer.Methods: This retrospective study enrolled 177 patients with histopathology-confirmed rectal adenocarcinoma (123 patients in the training cohort and 54 in the validation cohort). A total of 385 radiomics features were extracted from pretreatment T2W images. Five steps, including univariate statistical tests and a random forest algorithm, were performed to select the best preforming features for predicting SDM. Multivariate logistic regression analysis was conducted to build the clinical and clinical-radiomics combined models in the training cohort. The predictive performance was validated by receiver operating characteristics curve (ROC) analysis and clinical utility implementing a nomogram and decision curve analysis.Results: Fifty-nine patients (33.3%) were confirmed to have SDM. Six radiomics features and four clinical characteristics were selected for predicting SDM. The clinical-radiomics combined model performed better than the clinical model in both the training and validation datasets. A threshold of 0.44 yielded an area under the ROC (AUC) value of 0.827 (95% confidence interval (CI), 0.6963-0.9580), a sensitivity of 72.2%, a specificity of 94.4%, and an accuracy of 87.0% in the validation cohort for the combined model. A clinical-radiomics nomogram and decision curve analysis confirmed the clinical utility of the combined model.Conclusions: Our proposed clinical-radiomics combined model could be utilized as a noninvasive biomarker for identifying patients at high risk of SDM, which could aid in tailoring treatment strategies.Key Points: • T2WI-based radiomics analysis helps predict synchronous distant metastasis (SDM) of rectal cancer. • The clinical-radiomics combined model could be utilized as a noninvasive biomarker for predicting SDM. • Personalized treatment can be carried out with greater confidence based on the risk stratification for SDM in rectal cancer. [ABSTRACT FROM AUTHOR]

Fluoride phosphors with enhanced upconversion luminescence performance and multi-functionalization are urgently explored for applications in modern bio-detection and medical imaging. Here, a series of BaY 1- x Gd x F 5 : Yb/Er/Bi (0 ≤ x ≤ 0.5) solid solution nanocrystals are designed and synthesized. The influence of Gd3+-doping concentration on microstructure, upconversion luminescence, and magnetic performances are deeply reported. XRD results demonstrate the formation of solid solution with cubic phase structure. With increasing Gd3+ concentration, the diffraction angle gradually shifts toward lower direction as a result of replacing Y3+ by Gd3+ with larger ionic radius. Microstructure results show that the size distribution is between 60 and 100 nm and reveal that Gd3+ facilitates the growth of crystal grains. Upon 980 nm excitation, the BaY 1- x Gd x F 5 : Yb/Er/Bi samples demonstrate two dominant green and red emissions of Er3+ at 546 nm and 658 nm, respectively. By substituting Y3+ with Gd3+, the characteristic green luminescence can efficiently lead to an obvious enhancement at x = 0.2. The detailed enhancement mechanism is presented. Besides, the obtained nanocrystals show excellent paramagnetism properties, and the magnetic magnitude is significantly enhanced with increasing Gd3+ concentration. These results indicate that the BaY 1- x Gd x F 5 : Yb/Er/Bi nanocrystals are promising three-mode probes with potential applications in medical imaging and disease diagnosis. [Display omitted] • BaY 1- x Gd x F 5 nanocrystals show enhanced luminescence and magnetism properties. • The effect of Gd3+ on microstructure and properties is systematically studied. • The obtained nanocrystals exhibit potential application in multi-functional probes. [ABSTRACT FROM AUTHOR]

Strain engineering plays an important role in tuning electronic structure and improving catalytic capability of biocatalyst, but it is still challenging to modify the atomic-scale strain for specific enzyme-like reactions. Here, we systematically design Pt single atom (Pt 1 ), several Pt atoms (Pt n ) and atomically-resolved Pt clusters (Ptc) on PdAu biocatalysts to investigate the correlation between atomic strain and enzyme-like catalytic activity by experimental technology and in-depth Density Functional Theory calculations. It is found that Ptc on PdAu (Ptc-PA) with reasonable atomic strain upshifts the d-band center and exposes high potential surface, indicating the sufficient active sites to achieve superior biocatalytic performances. Besides, the Pd shell and Au core serve as storage layers providing abundant energetic charge carriers. The Ptc-PA exhibits a prominent peroxidase (POD)-like activity with the catalytic efficiency (K cat /K m ) of 1.50 × 10 9  mM -1  min -1 , about four orders of magnitude higher than natural horseradish peroxidase (HRP), while catalase (CAT)-like and superoxide dismutase (SOD)-like activities of Ptc-PA are also comparable to those of natural enzymes. Biological experiments demonstrate that the detection limit of the Ptc-PA-based catalytic detection system exceeds that of visual inspection by 132-fold in clinical cancer diagnosis. Besides, Ptc-PA can reduce multi-organ acute inflammatory damage and mitigate oxidative stress disorder., (© 2024. The Author(s).)

Intermetallic nanoparticles (NPs) possess significant potentials for catalytic applications, yet their production presents challenges as achieving the disorder-to-order transition during the atom ordering process involves overcoming a kinetic energy barrier. Here, we demonstrate a robust approach utilizing atomic gas-migration for the in-situ synthesis of stable and homogeneous intermetallic alloys for propane dehydrogenation (PDH). This approach relies on the physical mixture of two separately supported metal species in one reactor. The synthesized platinum-zinc intermetallic catalysts demonstrate exceptional stability for 1300 h in continuous propane dehydrogenation under industrially relevant industrial conditions, with extending 95% propylene selectivity and propane conversions approaching thermodynamic equilibrium values at 550-600  o C. In situ characterizations and density functional theory/molecular dynamics simulation reveal Zn atoms adsorb on the particle surface and then diffuse inward, aiding in the formation of ultrasmall and highly ordered intermetallic alloys. This in-situ gas-migration strategy is applicable to a wide range of intermetallic systems., (© 2024. The Author(s).)

In this study, novel ergosterol peroxide (EP) derivatives were synthesized and evaluated to assess their antiproliferative activity against four human cancer cell lines (A549, HepG2, MCF-7, and MDA-MB-231). Compound 3g exhibited the most potent antiproliferative activity, with an IC 50 value of 3.20 µM against MDA-MB-231. This value was 5.4-fold higher than that of the parental EP. Bioassay optimization further identified 3g as a novel glutaminase 1 (GLS1) inhibitor (IC 50 = 3.77 µM). In MDA-MB-231 cells, 3g reduced the cellular glutamate levels by blocking the glutamine hydrolysis pathway, which triggered reactive oxygen species production and induced caspase-dependent apoptosis. Molecular docking indicated that 3g interacts with the reaction site of the variable binding pocket by forming multiple interactions with GLS1. In a mouse model of breast cancer, 3g showed remarkable therapeutic effects at a dose of 50 mg/kg, with no apparent toxicity. Based on these results, 3g could be further evaluated as a novel GLS1 inhibitor for triple-negative breast cancer (TNBC) therapy.

Accumulating clinical evidence indicates that chronic exposure to retinoic acid (RA) may lead to depressive symptoms and even increase the risk of suicidal behavior, which severely limits the clinical long-term application of RA. The exact mechanisms through which RA contributes to the onset of depression remain largely unclear. Here, we administered intraperitoneal injections of all-trans RA to male C57BL/6 J mice over a period of 21 days. Mice subjected to chronic RA exposure displayed depressive-like behaviors, accompanied by impaired hippocampal neurogenesis and heightened RA receptor gamma (RARγ) levels in the ventral hippocampus (vHip). The administration of an RARγ antagonist effectively mitigated these RA-induced neurogenesis impairments and depressive-like behaviors. Chronic exposure to RA was also observed to promote hippocampal astrocytosis and increase astrocytic Rarγ expression in the ventral dentate gyrus (vDG) of hippocampus. Notably, astrocytic RARγ in the vDG was found to be a key factor in the observed hippocampal astrocytosis and neurogenesis impairments, and depressive-like behaviors. Chronic exposure to RA resulted in increased extracellular glutamate levels in neural stem cells (NSCs), accompanied by a decrease in glutamate transporter 1 (GLT-1) expression. Enhancing astrocytic GLT-1 expression was found to alleviate both hippocampal astrocytosis and depressive-like behaviors caused by RA. These findings underscore the critical role of astrocytic RARγ-GLT-1 axis in the development of hippocampal astrocytosis, neurogenesis impairments, and depressive symptoms, suggesting that targeting RARγ-GLT-1 could potentially offer an effective therapeutic approach for depression., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Purpose: Our study utilizes Mendelian Randomization (MR) to explore the causal relationships between a range of risk factors and preeclampsia, a major contributor to maternal and perinatal morbidity and mortality., Methods: Employing the Inverse Variance Weighting (IVW) approach, we conducted a comprehensive multi-exposure MR study analyzing genetic variants linked to 25 risk factors including metabolic disorders, circulating lipid levels, immune and inflammatory responses, lifestyle choices, and bone metabolism. We applied rigorous statistical techniques such as sensitivity analyses, Cochran's Q test, MR Egger regression, funnel plots, and leave-one-out sensitivity analysis to address potential biases like pleiotropy and population stratification., Results: Our analysis included 267,242 individuals, focusing on European ancestries and involving 2,355 patients with preeclampsia. We identified strong genetic associations linking increased preeclampsia risk with factors such as hyperthyroidism, BMI, type 2 diabetes, and elevated serum uric acid levels. Conversely, no significant causal links were found with gestational diabetes, total cholesterol, sleep duration, and bone mineral density, suggesting areas for further investigation. A notable finding was the causal relationship between systemic lupus erythematosus and increased preeclampsia risk, highlighting the significant role of immune and inflammatory responses., Conclusion: This extensive MR study sheds light on the complex etiology of preeclampsia, underscoring the causal impact of specific metabolic, lipid, immune, lifestyle, and bone metabolism factors. Our findings advocate for a multidimensional approach to better understand and manage preeclampsia, paving the way for future research to develop targeted preventive and therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tan, Ding, Shen, Huang, Li, Sun, Hong, Yang, He, Pei and Luo.)

This study aims to explore the effect and mechanism of a mitochondrion-targeted derivative of ergosterol peroxide(Mito-EP) on breast cancer. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of MDA-MB-231 cells treated with different concentrations(0, 0.075, 0.15, 0.3, 0.6, 1.2, and 2.4 μmol·L~(-1)) of Mito-EP. Cells were grouped for treatment with water(blank control), low, medium, and high concentrations(0.15, 0.3, and 0.6 μmol·L~(-1)) of Mito-EP, and ergosterol peroxide(EP)(0.6 μmol·L~(-1)). After the cells were treated for 48 h, flow cytometry was employed to examine the apoptosis rate, reactive oxygen species(ROS) level, mitochondrial membrane potential, and cell cycle distribution, and the apoptosis, ROS, and mitochondrial membrane potential were observed by laser confocal microscopy. A mouse model bearing subcutaneous xenograft tumor was established by injecting 4T1 cell suspension and used to study the inhibitory effect of Mito-EP on breast cancer. Western blot was employed to determine the protein levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), cleaved caspase-7, and cleaved caspase-9 in cells and the tumor tissue. The results showed that Mito-EP reduced the proliferation rate of MDA-MB-231 cells in a concentration-dependent manner. Compared with the blank control group, EP(0.6 μmol·L~(-1)) caused slight changes in the apoptosis rate, ROS level, and mitochondrial membrane potential. However, Mito-EP increased the apoptosis rate, elevated the ROS level, decreased mitochondrial membrane potential, up-regulated the protein levels of Bax, Cyt C, cleaved caspase-7, and cleaved caspase-9, and down-regulated the protein level of Bcl-2(all P&lt;0.05). Moreover, Mito-EP reduced the tumor volume and weight. In summary, Mito-EP may promote apoptosis in breast cancer cells by activating the mitochondrial apoptosis pathway.

Introduction: Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts., Methods: We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study., Results: One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0-3 was 58.4%., Conclusion: Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study., (© 2024. The Author(s).)

Lupeol is a natural pentacyclic triterpenoid with a wide range of biological activities. To improve the water solubility and targeting of lupeol, in the following study, we synthesized 27 lupeol derivatives in the first series by introducing lipophilic cations with lupeol as the lead compound. Through the screening of different cancer cells, we found that some of the derivatives showed better activity than cisplatin against human non-small cell lung cancer A549 cells, among which compound 6c was found to have an IC 50 value of 1.83 μM and a selectivity index of 21.02 (IC 50 MRC-5/IC 50 A549) against A549 cells. To further improve the antiproliferative activity of the compounds, we replaced the ester linkage of the linker with a carbamate linkage and synthesized a second series of five lupeol derivatives which were screened for activity, among which compound 14f was found to have an IC 50 value of 1.36 μM and a selectivity index of 15.60 (IC 50 MRC-5/IC 50 A549) against A549 cells. We further evaluated the bioactivity of compounds 6c and 14f and found that both compounds induced apoptosis in A549 cells, promoted an increase in intracellular reactive oxygen species and decrease in mitochondrial membrane potential, and inhibited the cell cycle in the S phase. Of the compounds, compound 14f showed stronger bioactivity than compound 6c. We then selected compound 14f for molecular-level Western blot evaluation and in vivo evaluation in the zebrafish xenograft A549 tumor cell model. Compound 14f was found to significantly downregulate Bcl-2 protein expression and upregulate Bax, Cyt C, cleaved caspase-9, and cleaved caspase-3 protein expression, and 14f was found to be able to inhibit the proliferation of A549 cells in the zebrafish xenograft model. The above results suggest that compound 14f has great potential in the development of antitumor drugs targeting mitochondria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recent nanopore sequencing system (R10.4) has enhanced base calling accuracy and is being increasingly utilized for detecting CpG methylation state. However, the robustness and universality of the methylation calling model in officially supplied Dorado remains poorly tested. In this study, we obtained heterogeneous datasets from human and plant sources to carry out comprehensive evaluations, which showed that Dorado performed significantly different across datasets. We therefore developed deep neural networks and implemented several optimizations in training a new model called DeepBAM. DeepBAM achieved superior and more stable performances compared with Dorado, including higher area under the ROC curves (98.47% on average and up to 7.36% improvement) and F1 scores (94.97% on average and up to 16.24% improvement) across the datasets. DeepBAM-based whole genome methylation frequencies have achieved >0.95 correlations with BS-seq on four of five datasets, outperforming Dorado in all instances. It enables unraveling allele-specific methylation patterns, including regions of transposable elements. The enhanced performance of DeepBAM paves the way for broader applications of nanopore sequencing in CpG methylation studies., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Porcine deltacoronavirus (PDCoV) is a newly discovered porcine intestinal pathogenic coronavirus with a single-stranded positive-sense RNA genome and an envelope. PDCoV infects pigs of different ages and causes acute diarrhea and vomiting in newborn piglets. In severe cases, infection leads to dehydration, exhaustion, and death in sick piglets, entailing great economic losses on pig farms. The clinical symptoms of PDCoV infection are very similar to those of other porcine enteroviruses. Although it is difficult to distinguish these viral infections without testing, monitoring PDCoV is very important because it can spread in populations. The most commonly used methods for the detection of PDCoV is qPCR, which is time-consuming and require skilled personnel and equipment. Many farms cannot meet the conditions required for detection. Therefore, it is necessary to establish a faster and more convenient method for detecting PDCoV., Aims: To establish a rapid and convenient detection method for PDCoV by combining RPA (Recombinase Polymerase Isothermal Amplification) with CRISPR/Cas13a., Methods: Specific RPA primers and crRNA for PDCoV were designed, and the nucleic acids in the samples were amplified with RPA. Fluorescent CRISPR/Cas13a detection was performed. We evaluated the sensitivity and specificity of the RPA-CRISPR/Cas13a assay using qPCR as the control method., Results: CRISPR/Cas13a-assisted detection was completed within 90 min. The minimum detection limit of PDCoV was 5.7 × 10 1 copies/μL. A specificity analysis showed that the assay did not cross-react with three other porcine enteroviruses., Conclusion: The RPA-CRISPR/Cas13a method has the advantages of high sensitivity, strong specificity, fast response, and readily accessible results, and can be used for the detection of PDCoV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Cheng, Wang, Yang, Zeng, Yang, Chen, Li and Liu.)

Purpose: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length., Study Design and Methods: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length., Results: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator., Conclusions: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging., Trial Registry: https://www.chictr.org.cn/showproj.html?proj=166181., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Despite extensive research on the relationship between choline and cardiovascular disease (CVD), conflicting findings have been reported. We aim to investigate the relationship between choline and CVD. Our analysis screened a retrospective cohort study of 14,663 participants from the National Health and Nutrition Examination Survey conducted between 2013 and 2018. Propensity score matching and restricted cubic splines was used to access the association between choline intake and the risk of CVD. A two-sample Mendelian randomization (MR) analysis was conducted to examine the potential causality. Additionally, sets of single cell RNA-sequencing data were extracted and analyzed, in order to explore the role of choline metabolism pathway in the progression and severity of the CVD and the underlying potential mechanisms involved. The adjusted odds ratios and 95% confidence intervals for stroke were 0.72 (0.53-0.98; p = 0.035) for quartile 3 and 0.54 (0.39-0.75; p < 0.001) for quartile 4. A stratified analysis revealed that the relationship between choline intake and stroke varied among different body mass index and waist circumference groups. The results of MR analysis showed that choline and phosphatidylcholine had a predominantly negative causal effect on fat percentage, fat mass, and fat-free mass, while glycine had opposite effects. Results from bioinformatics analysis revealed that alterations in the choline metabolism pathway following stroke may be associated with the prognosis. Our study indicated that the consumption of an appropriate quantity of choline in the diet may help to protect against CVD and the effect may be choline-mediated, resulting in a healthier body composition. Furthermore, the regulation of the choline metabolism pathway following stroke may be a promising therapeutic target., (© 2024. The Author(s).)

Background and Aim: Transmissible gastroenteritis virus (TGEV) is a highly contagious gastrointestinal virus that causes diarrhea, vomiting, anorexia, dehydration, and weight loss in piglets. In clinical practice, it often occurs in mixed infections with other pathogens, and is therefore difficult to diagnose and prevent. It mainly harms piglets of about 2 weeks old, causing huge losses on farms. The clinical confirmation of TGEV usually requires a laboratory diagnosis, but traditional PCR and immunofluorescence assays have some limitations. Moreover, most farms in China are ill-equipped to accurately diagnose the disease. Therefore, a new detection method with high sensitivity and specificity and less dependence on instrumentation is required., Methods: We used recombinase polymerase amplification (RPA), combined with the nuclease characteristics of the activated Cas13a protein to establish a visual CRISPR-Cas13a-assisted detection method for TGEV by adding a reporter RNA with fluorescent and quenching moieties to the system., Result: We selected the optimal RPA primer and best CRISPR RNA (crRNA). The reaction system was optimized and its repeatability, specificity, and sensitivity verified. The TGEV detection system did not cross-react with other common diarrhea viruses, and its detection limit was 10 1 copies, which is similar with the sensitivity of qPCR. We successfully established an RPA-CRISPR-Cas13a-assisted detection method, and used this detection system to analyze 123 pig blood samples. qPCR was used as the gold standard method. The sensitivity, specificity, positive coincidence rate, and negative coincidence rate of the new method were 100, 98.93, 96.66, and 100%, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Cheng, Luo, Yang, Zeng, Yang, Chen, Li and Liu.)

This study investigated the effects of ergosterol peroxide(EP) on the proliferation and apoptosis of MCF-7 breast cancer cells, explored its possible mechanisms of action, and verified the effects and mechanisms by in vitro experiments. Network pharmaco-logy was used to screen the target proteins of EP and construct target networks and protein-protein interaction(PPI) networks to predict the potential target proteins and related pathways involved in EP anti-breast cancer effects. The MTT assay was performed to measure the inhibitory effect of EP on MCF-7 cell proliferation, and the colony formation assay was used to assess the cell cloning ability. Flow cytometry and laser confocal microscopy were employed to evaluate cell apoptosis, mitochondrial membrane potential and reactive oxygen species(ROS) levels. Western blot analysis was conducted to examine the expression levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), caspase-7, cleaved caspase-7, phosphatidylinositol 3-kinase(PI3K), and se-rine/threonine kinase B(AKT) in MCF-7 cells treated with EP. The results of network pharmacology prediction yielded 173 common targets between EP and breast cancer; the results of Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis showed that EP treatment for breast cancer mainly affected the signaling pathways such as cancer pathway, PI3K-AKT signaling pathway, cellular senescence signaling pathway, and viral carcinogenesis pathway; and the MTT assay results showed that the viability of MCF-7 cells in the EP group was significantly lower than that in the control group, exhibiting a time-and concentration-dependent trend, and EP can inhibit colony formation of MCF-7 breast cancer cells. Treatment with 10, 20, and 40 μmol·L~(-1) EP for 24 h resulted in a significant increase in the total apoptosis rate of MCF-7 cells, a significant decrease in mitochondrial membrane potential, and a significant increase in ROS levels. In addition, treatment with EP led to an upregulation of Cyt C, Bax, and cleaved caspase-7 protein expression, and a downregulation of p-PI3K, p-AKT, and Bcl-2 protein expression in MCF-7 cells. Studies have shown that EP inhibits MCF-7 breast cancer cell proliferation and reduces colony formation by a mechanism that may be related to the PI3K-AKT pathway mediating the mitochondrial apoptotic pathway.

Background: Despite observational links between serum uric acid (SUA), sex hormone-related phenotypes, and female infertility, the causality behind these associations remains uncertain., Objective: This study utilizes Bidirectional Two-Sample and Mediation Mendelian Randomization to explore the causal relationships and mediation effects of sex hormone-binding globulin (SHBG), total testosterone (TT), and estradiol on these associations., Methods: We analyzed single-nucleotide polymorphisms (SNPs) associated with SUA and sex hormone levels using data from large-scale GWAS of European populations. Female infertility data were sourced from 6,481 cases and 75,450 controls in the FinnGen Consortium. We employed methods including Inverse Variance Weighted (IVW), Weighted Median, and MR-Egger regression to assess causality., Results: We found that elevated SUA levels causally increase the risk of female infertility (IVW OR: 1.13, P=0.047). Elevated SUA levels significantly decrease SHBG levels (β=-0.261; P=2.177e-04), with SHBG mediating 27.93% of the effect of SUA on infertility (OR=0.854; 95%CI, 0.793-0.920; P=2.853e-05). Additionally, elevated TT levels, which were associated with decreased SUA levels (β=-0.127), showed an indirect effect on infertility mediated by SUA (β=-0.0187; 95% CI, -0.041 to -0.003; P=0.046)., Conclusion: Our findings demonstrate causal links between high SUA and increased risk of female infertility mediated by hormonal factors such as SHBG and TT. These insights suggest new avenues for infertility treatment and highlight the need for further research into these mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tan, Shen, Huang, Li, Ding, Sun, Hong, Yang, He, Zhu and Luo.)

This study aims to investigate the effect of ergosterol peroxide(EP) on the apoptosis of human hepatocellular carcinoma and its mechanism of action. The cell viability of HepG2 and SK-Hep-1 cells with 0(blank control), 2.5, 5, 10, 20, 40, and 80 μmol·L~(-1) of EP after 24, 48, and 72 h of action was detected by using CCK-8 assay, and the half inhibitory concentrations(IC&#95;(50)) at 24, 48, and 72 h were calculated. Formal experiments were performed to detect the effect of EP on intracellular reactive oxygen species(ROS) using DCFH-DA staining, the effect of EP on intracellular mitochondrial membrane potential using JC-1 staining, the number of apoptotic cells using Annexin V-FITC/PI double-staining after HepG2 cells were co-cultured with 0(blank control), 10, 20, 40 μmol·L~(-1) EP for 48 h. The effects of EP at different concentrations on apoptotic morphology were detected using AO/EB staining. The effects of different concentrations of EP on the protein expression of mitochondrial apoptosis pathway-related proteins B cell lymphoma 2(Bcl-2), cytochrome C(Cyt-C), Bcl-2-related X protein(Bax), caspase-3, cleaved caspase-3, caspase-9, and cleaved caspase-9 were examined by using Western blot. The results showed that different concentrations of EP could inhibit the proliferation of hepatocellular carcinoma with concentration-and time-dependent trends. Compared with the blank control group, the ROS level in the EP-treated group increased significantly(P&lt;0.05). The mitochondrial membrane potential decreased significantly(P&lt;0.05). The total apoptosis rate increased significantly(P&lt;0.05). The expression of Bcl-2 protein was significantly down-regulated, and the expression of Cyt-C, Bax, cleaved caspase-9, and cleaved caspase-3 were significantly up-regulated(P&lt;0.05). In summary, EP may inhibit the proliferation of hepatocellular carcinoma by modulating the mitochondria-mediated apoptosis pathway and induce apoptosis.

Background: Renal tertiary lymphoid structures (TLSs) are involved in renal pathology and prognosis of IgA nephropathy (IgAN). CD30 and its ligands participate in the formation of renal TLSs. However, the relationship between circulating CD30 and renal prognosis is unclear. The objective of this study was to evaluate the relationship between circulating CD30 and prognosis in patients with IgAN., Methods: We conducted a retrospective study including 351 patients with biopsy proved IgAN. We collected clinical and pathologic features at the time of biopsy and recorded renal follow-up outcomes. Circulating CD30 levels in IgAN patients at the time of biopsy were measured via enzyme-linked immunosorbent assay (ELISA). The association between elevated CD30 levels and the composite endpoint (defined as a ≥ 50 % decline in eGFR from baseline, end-stage renal disease, or death) was investigated using Cox regression analysis., Results: During a median follow-up period of 5.12 years, 44 (12.5 %) patients in the cohort reached the composite endpoint. Kaplan-Meier survival curve analysis revealed a significant association between higher circulating CD30 levels and a poorer renal prognosis (log-rank P < 0.001). Cox regression analysis showed that high CD30 was an independent factor for the composite endpoints in multivariable-adjusted models (HR 3.397, 95 % CI: 1.230-9.384, P = 0.018). These associations were also observed in a subgroup of patients with concomitant renal TLSs formation (10.443, 95 % CI: 1.680-65.545, P = 0.012), proteinuria > 1 g/d (HR 12.287, 95 % CI: 1.499-100.711, P = 0.019), and female patients (HR 22.372, 95 % CI: 1.797-278.520, P = 0.016)., Conclusion: Elevated level of circulating CD30 is an independent risk factor for renal disease progression in patients with IgAN., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Perovskite bandgap tuning without quality loss makes perovskites unique among solar absorbers, offering promising avenues for tandem solar cells 1,2 . However, minimizing the voltage loss when their bandgap is increased to above 1.90 eV for triple-junction tandem use is challenging 3-5 . Here we present a previously unknown pseudohalide, cyanate (OCN - ), with a comparable effective ionic radius (1.97 Å) to bromide (1.95 Å) as a bromide substitute. Electron microscopy and X-ray scattering confirm OCN incorporation into the perovskite lattice. This contributes to notable lattice distortion, ranging from 90.5° to 96.6°, a uniform iodide-bromide distribution and consistent microstrain. Owing to these effects, OCN-based perovskite exhibits enhanced defect formation energy and substantially decreased non-radiative recombination. We achieved an inverted perovskite (1.93 eV) single-junction device with an open-circuit voltage (V OC ) of 1.422 V, a V OC  × FF (fill factor) product exceeding 80% of the Shockley-Queisser limit and stable performance under maximum power point tracking, culminating in a 27.62% efficiency (27.10% certified efficiency) perovskite-perovskite-silicon triple-junction solar cell with 1 cm 2 aperture area., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The ability of generating effective humoral immune responses to SARS-CoV-2 infection has not been clarified in lymphoma patients. The study aimed to investigate the antibody (Ab) production after SARS-Cov-2 infection and clarify the factors affecting the Ab generation in these patients., Patients & Methods: 80 lymphoma patients and 51 healthy controls were included in this prospective observational study. Clinical factors and treatment regimens affecting Ab positive rate (APR) and Ab levels were analyzed by univariate and multivariate methods., Results: The anti-SARS-CoV-2 IgG APR and Ab levels in lymphoma patients were significantly lower than those in healthy controls. Lymphoma patients with COVID-19 vaccination had significantly higher APR and Ab levels compared with those without vaccination. Additionally, the use of dexamethasone for COVID-19 treatment had a negative impact on Ab levels. For the impact of treatment regimens on the APR and Ab levels, the results showed that patients treated with ≥ 6 times CD20 monoclonal Ab (mAb) and patients treated with autologous hematopoietic stem cell transplantation (ASCT) prior to infection produced a statistically lower APR and Ab levels compared with those treated with 1-5 times CD20 mAb and those treated without ASCT, respectively. Furthermore, multiple regression analysis indicated that the number of anti-CD20 treatment was an independent predictor for both APR and Ab levels., Conclusions: Humoral immune response to SARS-CoV-2 infection was impaired in lymphoma patients partly due to anti-CD20 and ASCT treatment. COVID-19 vaccination may be more needed for these patients., (© 2024. The Author(s).)

The strong promotion effects of alkali/alkaline earth metals are frequently reported for heterogeneous catalytic processes such as propane dehydrogenation (PDH), but their functioning principles remain elusive. This paper describes the effect of the addition of calcium (Ca) on reducing the deactivation rate of platinum-tin (Pt-Sn) catalyzed PDH from 0.04 h -1 to 0.0098 h -1 at 873 K under a WHSV of 16.5 h -1 of propane. The Pt-Sn-Ca catalyst shows a high propylene selectivity of >96% with a propylene production rate of 41 mol C 3 H 6 (g Pt h) -1 and ∼1% activity loss after regeneration. The combination of characterization and DFT simulations reveals that Ca acts as a structural promoter favoring the transition of Sn n + in the parent catalyst to Sn 0 during reduction, and the latter is an electron donor that increases the electron density of Pt. This greatly suppresses coke formation from deep dehydrogenation. Moreover, it was found that Ca promotes the formation of a highly reactive and sintering-resistant sub-nano Pt-Sn alloy with a diameter of approximately 0.8 nm. These lead to high activity and selectivity for the Pt-Sn-Ca catalyst for PDH., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Intracerebral hemorrhage is a highly prevalent and prognostically poor disease, imposing immeasurable harm on human life and health. However, the treatment options for intracerebral hemorrhage are severely limited, particularly in terms of improving the microenvironment of the lesion, promoting neuronal cell survival, and enhancing neural function. This review comprehensively discussed the application of stem cell therapy for intracerebral hemorrhage, providing a systematic summary of its developmental history, types of transplants, transplantation routes, and transplantation timing. Moreover, this review presented the latest research progress in enhancing the efficacy of stem cell transplantation, including pretransplantation preconditioning, genetic modification, combined therapy, and other diverse strategies. Furthermore, this review pioneeringly elaborated on the barriers to clinical translation for stem cell therapy. These discussions were of significant importance for promoting stem cell therapy for intracerebral hemorrhage, facilitating its clinical translation, and improving patient prognosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chimeric antigen receptor (CAR) cell therapy is a great success and breakthrough in immunotherapy. However, there are still lots of barriers to its wide use in clinical, including long time consumption, high cost, and failure against solid tumors. For these challenges, researches are deplored to explore CAR cells to more appliable products in clinical. This minireview focuses on the advanced non-viral materials for CAR-T transfection ex vivo with better performance, delivery systems combined with other therapy for enhancement of CAR-T therapy in solid tumors. In addition, the targeted delivery platform for CAR cells in vivo generation as a breakthrough technology as its low cost and convenience. In the end, the prospective direction and future of CAR cell therapy are discussed., (© 2023 Wiley-VCH GmbH.)

Background: The volume doubling time (VDT) of breast cancer was most frequently calculated using the two-dimensional (2D) diameter, which is not reliable for irregular tumors. It was rarely investigated using three-dimensional (3D) imaging with tumor volume on serial magnetic resonance imaging (MRI)., Purpose: To investigate the VDT of breast cancer using 3D tumor volume assessment on serial breast MRIs., Study Type: Retrospective., Subjects: Sixty women (age at diagnosis: 57 ± 10 years) with breast cancer, assessed by two or more breast MRI examinations. The median interval time was 791 days (range: 70-3654 days)., Field Strength/sequence: 3-T, fast spin-echo T2-weighted imaging (T2WI), single-shot echo-planar diffusion-weighted imaging (DWI), and gradient echo dynamic contrast-enhanced imaging., Assessment: Three radiologists independently reviewed the morphological, DWI, and T2WI features of lesions. The whole tumor was segmented to measure the volume on contrast-enhanced images. The exponential growth model was fitted in the 11 patients with at least three MRI examinations. The VDT of breast cancer was calculated using the modified Schwartz equation., Statistical Tests: Mann-Whitney U test, Kruskal-Wallis test, Chi-squared test, intraclass correlation coefficients, and Fleiss kappa coefficients. A P-value <0.05 was considered statistically significant. The exponential growth model was evaluated using the adjusted R 2 and root mean square error (RMSE)., Results: The median tumor diameter was 9.7 mm and 15.2 mm on the initial and final MRI, respectively. The median adjusted R 2 and RMSE of the 11 exponential models were 0.97 and 15.8, respectively. The median VDT was 540 days (range: 68-2424 days). For invasive ductal carcinoma (N = 33), the median VDT of the non-luminal type was shorter than that of the luminal type (178 days vs. 478 days). On initial MRI, breast cancer manifesting as a focus or mass lesion showed a shorter VDT than that of a non-mass enhancement (NME) lesion (median VDT: 426 days vs. 665 days)., Data Conclusion: A shorter VDT was observed in breast cancer manifesting as focus or mass as compared to an NME lesion., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Direct propane dehydrogenation (PDH) to propylene is a desirable commercial reaction but is highly endothermic and severely limited by thermodynamic equilibrium. Routes that oxidatively remove hydrogen as water have safety and cost challenges. We coupled chemical looping-selective hydrogen (H 2 ) combustion and PDH with multifunctional ferric vanadate-vanadium oxide (FeVO 4 -VO x ) redox catalysts. Well-dispersed VO x supported on aluminum oxide (Al 2 O 3 ) provides dehydrogenation sites, and adjacent nanoscale FeVO 4 acts as an oxygen carrier for subsequent H 2 combustion. We achieved an integral performance of 81.3% propylene selectivity at 42.7% propane conversion at 550°C for 200 chemical looping cycles for the reoxidization of FeVO 4 . Based on catalytic experiments, spectroscopic characterization, and theory calculations, we propose a hydrogen spillover-mediated coupling mechanism. The hydrogen species generated at the VO x sites migrated to adjacent FeVO 4 for combustion, which shifted PDH toward propylene. This mechanism is favored by the proximity between the dehydrogenation and combustion sites.

Tertiary lymphoid structure (TLS) represents lymphocyte clusters in non-lymphoid organs. The formation and maintenance of TLS are dependent on follicular helper T (TFH) cells. However, the role of TFH cells during renal TLS formation and the renal fibrotic process has not been comprehensively elucidated in chronic kidney disease. Here, we detected the circulating TFH cells from 57 IgAN patients and found that the frequency of TFH cells was increased in IgA nephropathy patients with renal TLS and also increased in renal tissues from the ischemic-reperfusion-injury (IRI)-induced TLS model. The inducible T-cell co-stimulator (ICOS) is one of the surface marker molecules of TFH. Remarkably, the application of an ICOS-neutralizing antibody effectively prevented the upregulation of TFH cells and expression of its canonical functional mediator IL-21, and also reduced renal TLS formation and renal fibrosis in IRI mice in vivo. In the study of this mechanism, we found that recombinant IL-21 could directly promote renal fibrosis and the expression of p65. Furthermore, BAY 11-7085, a p65 selective inhibitor, could effectively alleviate the profibrotic effect induced by IL-21 stimulation. Our results together suggested that TFH cells contribute to TLS formation and renal fibrosis by IL-21. Targeting the ICOS-signaling pathway network could reduce TFH cell infiltration and alleviate renal fibrosis.

The objective of this study is to develop a radiomic signature constructed from deep learning features and a nomogram for prediction of axillary lymph node metastasis (ALNM) in breast cancer patients. Preoperative magnetic resonance imaging data from 479 breast cancer patients with 488 lesions were studied. The included patients were divided into two cohorts by time (training/testing cohort, n = 366/122). Deep learning features were extracted from diffusion-weighted imaging-quantitatively measured apparent diffusion coefficient (DWI-ADC) imaging and dynamic contrast-enhanced MRI (DCE-MRI) by a pretrained neural network of DenseNet121. After the selection of both radiomic and clinicopathological features, deep learning signature and a nomogram were built for independent validation. Twenty-three deep learning features were automatically selected in the training cohort to establish the deep learning signature of ALNM. Three clinicopathological factors, including LN palpability (odds ratio (OR) = 6.04; 95% confidence interval (CI) = 3.06-12.54, P = 0.004), tumor size in MRI (OR = 1.45, 95% CI = 1.18-1.80, P = 0.104), and Ki-67 (OR = 1.01; 95% CI = 1.00-1.02, P = 0.099), were selected and combined with radiomic signature to build a combined nomogram. The nomogram showed excellent predictive ability for ALNM (AUC 0.80 and 0.71 in training and testing cohorts, respectively). The sensitivity, specificity, and accuracy were 65%, 80%, and 75%, respectively, in the testing cohort. MRI-based deep learning radiomics in patients with breast cancer could be used to predict ALNM, providing a noninvasive approach to structuring the treatment strategy., (© 2023. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Propane dehydrogenation (PDH) is an industrial technology for direct propylene production which has received extensive attention in recent years. Nevertheless, existing non-oxidative dehydrogenation technologies still suffer from the thermodynamic equilibrium limitations and severe coking. Here, we develop the intensified propane dehydrogenation to propylene by the chemical looping engineering on nanoscale core-shell redox catalysts. The core-shell redox catalyst combines dehydrogenation catalyst and solid oxygen carrier at one particle, preferably compose of two to three atomic layer-type vanadia coating ceria nanodomains. The highest 93.5% propylene selectivity is obtained, sustaining 43.6% propylene yield under 300 long-term dehydrogenation-oxidation cycles, which outperforms an analog of industrially relevant K-CrO x /Al 2 O 3 catalysts and exhibits 45% energy savings in the scale-up of chemical looping scheme. Combining in situ spectroscopies, kinetics, and theoretical calculation, an intrinsically dynamic lattice oxygen "donator-acceptor" process is proposed that O 2- generated from the ceria oxygen carrier is boosted to diffuse and transfer to vanadia dehydrogenation sites via a concerted hopping pathway at the interface, stabilizing surface vanadia with moderate oxygen coverage at pseudo steady state for selective dehydrogenation without significant overoxidation or cracking., (© 2023. The Author(s).)

Background: Various features extracted from breast MRI have the potential to serve as noninvasive biomarkers for the prediction of the biologic behavior of breast cancer. The purpose of this study was to investigate the value of focal breast edema and breast edema score (BES) on T2-weighted images in providing valuable biological information for breast cancer patients' personalized treatment., Method: Two hundred and five lesions in 201 patients with invasive breast cancer confirmed by surgery or biopsy in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from November 2018 to October 2019 were retrospectively recruited and analyzed in this study. Focal edema and BES were evaluated at fat-suppressed T2 weighted imaging. All the lesions were divided into two groups according to the presence of focal edema. The differences in clinicopathological characteristics between the two groups and between different BES were compared., Results: Two hundred and five lesions in 201 patients with invasive breast cancer were retrospectively recruited and analyzed in this study. On the fat-suppressed T2WI, focal edema was detected in 102 of 205 lesions (49.8%). BES was positively correlated with tumor size (p < 0.001), histologic grade (p = 0.006), Ki-67 index (p < 0.001), and N stage (p = 0.007), and was negatively correlated with expression of ER and PR (p < 0.001). Higher BES was more likely to present in patients with non-luminal breast cancer (p < 0.001) and suggested the possibility of a higher N stage., Conclusions: Focal edema on T2WI of breast MRI indicates stronger tumor invasiveness, in which non-luminal breast cancer is more inclined to present focal edema. Breast edema score, a novel and practical tool, helps guide the individualized treatment of patients with invasive breast cancer., Critical Relevance Statement: Focal edema on T2WI of breast MRI indicates stronger tumor invasiveness. Breast edema score helps guide the individualized treatment of patients with invasive breast cancer., (© 2023. The Author(s).)

Difficulty in swallowing is a common symptom in stroke patients, and nasogastric tubes are routinely used to solve the nutritional support problem of these patients. The existing nasogastric tube have the disadvantages of causing aspiration pneumonia and patient discomfort. The traditional transoral gastric tube has no one-way valve switch and gastric content storage device, and cannot be fixed in the stomach, resulting in reflux of gastric contents, inability to fully understand the digestion and absorption of gastric contents, and accidental dislocation of the gastric tube, affecting further feeding and gastric content detection. For these reasons, the medical staff of the department of gastroenterology and colorectal surgery of Jilin University China-Japan Union Hospital designed a new transoral gastric tube that can extract and store gastric contents, and was granted a national utility model patent of China (ZL 2020 2 1704393.1). The device consists of collection, cannula and fixation modules. The collection module includes three parts. Gastric contents storage capsule, which can clearly visualize the gastric contents; three-way switch, which can be controlled by rotating the pathway, makes the pathway exist in different states, which is convenient for medical personnel to extract gastric juice, as well as perform intermittent oral tube feeding on the patient or close the pipeline, and reduce contamination and prolong the service life of the gastric tube; one-way valve, which can effectively avoid the contents of the reflux back into the stomach. The tube insertion module includes three parts. A graduated tube, which can enable the medical staff to effectively identify the insertion depth; a solid guide head, which makes the insertion of the tube through the mouth more smoothly; the gourd-shaped passageway, which effectively avoids the blockage of the tube. The fixation module is a water-filled balloon, which is properly filled with water and air. After the pipe is inserted through the mouth, it can be injected with water and gas properly to avoid accidental withdrawal of the gastric tube. Intermittent oroesophageal tube feeding of patients with dysphagia after stroke through a transoral gastric tube that can extract and store gastric contents can not only accelerate the recovery process of patients and shorten the hospitalization time, but also transoral enteral nutrition can effectively promote the recovery of patients' systemic systems, which has certain clinical use value.