Novel pathological variants of NHP2 affect N-terminal domain flexibility, protein stability, H/ACA Ribonucleoprotein (RNP) complex formation and telomerase activity.

Telomere biology disorders (TBDs) are characterized by short telomeres, premature aging, bone marrow failure and cancer predisposition. Germline mutations in NHP2, encoding for one component of the telomerase cofactor H/ACA RNA binding complex together with Dyskerin, NOP10 and GAR1, have been previously reported in rare cases of TBDs. Here, we report two novel NHP2 variants (NHP2-A39T and NHP2-T44M) identified in a compound heterozygous patient affected by premature aging, bone marrow failure/myelodysplastic syndrome and gastric cancer. Although still able to support cell viability, both variants reduce the levels of hTR, the telomerase RNA component, and telomerase activity, expanding the panel of NHP2 pathological variants. Furthermore, both variants fail to be incorporated in the H/ACA RNA binding complex when in competition with wild-type endogenous NHP2, and the lack of incorporation causes their drastic proteasomal degradation. By RoseTTAFold prediction followed by molecular dynamics simulations, we reveal a dramatic distortion of residues 33-41, which normally position on top of the NHP2 core, as the main defect of NHP2-A39T, and high flexibility and the misplacement of the N-terminal region (residues 1-24) in NHP2-T44M and, to a lower degree, in NHP2-A39T. Because deletion of amino acids 2-24 causes a reduction in NHP2 levels only in the presence of wild-type NHP2, while deletion of amino acids 2-38 completely disrupts NHP2 stability, we propose that the two variants are mis-incorporated into the H/ACA binding complex due to the altered dynamics of the first 23 amino acids and/or the distortion of the residues 25-41 loop.

Venetoclax plus a hypomethylating agent versus cytarabine, aclarubicin, and granulocyte colony-stimulating factor chemotherapy as a first-line therapy for newly diagnosed acute myeloid leukemia: A propensity score-matched analysis.

BACKGROUND: Both venetoclax plus a hypomethylating agent (VEN/HMA) and cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG) are low-intensity regimens for older patients with acute myeloid leukemia (AML) that show good efficacy and safety. It is unknown how VEN/HMA compares with the CAG regimen for the treatment of newly diagnosed AML. METHODS: The outcomes of patients with newly diagnosed AML treated with VEN/HMA were compared with those of patients treated with a CAG-based regimen. Propensity score matching between these two cohorts at a 1:1 ratio was performed according to age at diagnosis, sex, Eastern Cooperative Oncology Group performance status, state of fitness, and European LeukemiaNet (ELN) 2022 risk stratification to minimize bias. RESULTS: A total of 84 of 96 patients in the VEN/HMA cohort were matched with 84 of 147 patients in the CAG cohort. VEN/HMA resulted in a better response than the CAG-based regimens, as indicated by a higher composite complete remission (CRc) rate (82.1% vs. 60.7%; p = .002) and minimal residual disease negativity rate (88.2% vs. 68.2%; p = .009). In patients with an ELN adverse risk, VEN/HMA was associated with a higher CRc rate compared to CAG (80.5% vs. 58.3%; p = .006). VEN/HMA was associated with longer event-free survival (EFS) (median EFS, not reached vs. 4.5 months; p = .0004), whereas overall survival (OS) was comparable between the two cohorts (median OS, not reached vs. 18 months; p = .078). CONCLUSIONS: The VEN/HMA regimen may result in a better response than CAG-based treatment in older patients with newly diagnosed AML.

Comprehensive analysis and prediction model of mitophagy and ferroptosis in primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is linked to specific pathogenic mechanisms, yet its relationship with mitophagy and ferroptosis is poorly understood. This study aimed to identify new biomarkers and explore the role of mitophagy and ferroptosis in ITP pathogenesis. Techniques such as differential analysis, Mfuzz expression pattern clustering, machine learning, gene set enrichment analysis, single-cell RNA sequencing (scRNA-seq) and immune infiltration analysis were employed to investigate the molecular pathways of pivotal genes. Two-sample Mendelian randomization (TSMR) assessed the causal effects in ITP. Key genes identified in the training set included GABARAPL1, S100A8, LIN28A, and GDF9, which demonstrated diagnostic potential in validation sets. Functional analysis indicated these genes' involvement in ubiquitin phosphorylation, PPAR signalling pathway and T-cell differentiation. Immune infiltration analysis revealed increased macrophage presence in ITP, related to the critical genes. scRNA-seq indicated reduced GABARAPL1 expression in ITP bone marrow macrophages. TSMR linked S100A8 with ITP diagnosis, presenting an OR of 0.856 (95% CI = 0.736-0.997, p = 0.045). The study pinpointed four central genes, GABARAPL1, S100A8, LIN28A, and GDF9, tied to mitophagy and ferroptosis in ITP. It posits that diminished GABARAPL1 expression may disrupts ubiquitin phosphorylation and PPAR signalling, impairing mitophagy and inhibiting ferroptosis, leading to immune imbalance.

Thrombopoietin improves the functions of bone marrow endothelial progenitor cells via METTL16/Akt signalling of haematological patients with chemotherapy-induced thrombocytopenia.

Bone marrow endothelial progenitor cells (BM EPCs) are crucial in supporting haematopoietic regeneration, while the BM EPCs of haematological patients with chemotherapy-induced thrombocytopenia (CIT) are unavoidably damaged. Therefore, the present study aimed to examine the effect of thrombopoietin (TPO) on the recovery of BM EPCs of CIT patients and to identify the underlying mechanisms. The cell functions were determined by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil)-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake and fluorescein isothiocyanate (FITC)-labeled Ulex europaeus agglutinin-I (FITC-UEA-I) binding assay, as well as proliferation, migration and tube formation experiments. Endothelial cells were transfected with METTL16 lentivirus, followed by methylated RNA immunoprecipitation sequencing. Zebrafish with vascular defect was used as the in vivo model. TPO significantly improved the quantity and functions of BM EPCs from CIT patients in vitro and restored the subintestinal vein area of zebrafish with vascular defect in vivo. Mechanically, TPO enhanced the BM EPC functions through Akt signal mediated by METTL16, which was downregulated in BM EPCs of CIT patients and involved in the regulation of endothelial functions. The present study demonstrates that TPO improves the recovery of BM EPCs from CIT patients with haematological malignancies via METTL16/Akt signalling, which provides new insights into the role of TPO in treating CIT in addition to direct megakaryopoiesis.

Hepatic mitochondrial NAD + transporter SLC25A47 activates AMPKα mediating lipid metabolism and tumorigenesis.

BACKGROUND AIMS: SLC25A47 was initially identified as a mitochondrial HCC-downregulated carrier protein, but its physiological functions and transport substrates are unknown. We aimed to investigate the physiological role of SLC25A47 in hepatic metabolism. APPROACH RESULTS: In the treatment of hepatocytes with metformin, we found that metformin can transcriptionally activate the expression of Slc25a47 , which is required for AMP-activated protein kinase α (AMPKα) phosphorylation. Slc25a47 -deficient mice had increased hepatic lipid content, triglycerides, and cholesterol levels, and we found that Slc25a47 deficiency suppressed AMPKα phosphorylation and led to an increased accumulation of nuclear SREBPs, with elevated fatty acid and cholesterol biosynthetic activities. Conversely, when Slc25a47 was overexpressed in mouse liver, AMPKα was activated and resulted in the inhibition of lipogenesis. Moreover, using a diethylnitrosamine-induced mouse HCC model, we found that the deletion of Slc25a47 promoted HCC tumorigenesis and development through the activated mammalian target of rapamycin cascade. Employing homology modeling of SLC25A47 and virtual screening of the human metabolome database, we demonstrated that NAD + was an endogenous substrate for SLC25A47, and the activity of NAD + -dependent sirtuin 3 declined in Slc25a47 -deficient mice, followed by inactivation of AMPKα. CONCLUSIONS: Our findings reveal that SLC25A47, a hepatocyte-specific mitochondrial NAD + transporter, is one of the pharmacological targets of metformin and regulates lipid homeostasis through AMPKα, and may serve as a potential drug target for treating NAFLD and HCC.

Manganese-derived biomaterials for tumor diagnosis and therapy.

Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.

Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application.

Malignancy is a major public health problem and among the leading lethal diseases worldwide. Although the current tumor treatment methods have therapeutic effect to a certain extent, they still have some shortcomings such as poor water solubility, short half-life, local and systemic toxicity. Therefore, how to deliver therapeutic agent so as to realize safe and effective anti-tumor therapy become a problem urgently to be solved in this field. As a medium of information exchange and material transport between cells, exosomes are considered to be a promising drug delivery carrier due to their nano-size, good biocompatibility, natural targeting, and easy modification. In this review, we summarize recent advances in the isolation, identification, drug loading, and modification of exosomes as drug carriers for tumor therapy alongside their application in tumor therapy. Basic knowledge of exosomes, such as their biogenesis, sources, and characterization methods, is also introduced herein. In addition, challenges related to the use of exosomes as drug delivery vehicles are discussed, along with future trends. This review provides a scientific basis for the application of exosome delivery systems in oncological therapy.

Clinic, CT radiomics, and deep learning combined model for the prediction of invasive pulmonary aspergillosis.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a serious fungal infection. However, current diagnostic methods have limitations. The purpose of this study was to use artificial intelligence to achieve a more accurate diagnosis of IPA. METHODS: Totally 263 patients (148 cases of IPA, 115 cases of non-IPA) were retrospectively enrolled from a single institution and randomly divided into training and test sets at a ratio of 7:3. Clinic-radiological independent risk factors for IPA were screened using univariate analysis and multivariate logistic regression analysis, after which a clinic-radiological model was constructed. The optimal radiomics features were extracted and screened based on CT images to construct the radiomics label score (Rad-score) and radiomics model. The optimal DL features were extracted and screened using four pre-trained convolutional neural networks, respectively, followed by the construction of the DL label score (DL-score) and DL model. Then, the radiomics-DL model was constructed. Finally, the combined model was constructed based on clinic-radiological independent risk factors, the Rad-score, and the DL-score. LR was adopted as the classifier. Receiver operating characteristic (ROC) curves were drawn, and the areas under the curve (AUC) were calculated to evaluate the efficacy of each model in predicting IPA. Additionally, based on the best-performing model on the LR classifier, four other machine learning (ML) classifiers were constructed to evaluate the predictive value for IPA. RESULTS: The AUC of the clinic-radiological model for predicting IPA in the training and test sets was 0.845 and 0.765, respectively. The AUC of the radiomics-DL and combined models in the training set was 0.871 and 0.932, while in the test set was 0.851 and 0.881, respectively. The combined model showed better predictive performance than all other models. DCA showed that taking 0.00-1.00 as the threshold, the clinical benefit of the combined model was higher than that of all other models. Then, the combined model was trained on four other machine learning classifiers, all of which achieved AUC values above 0.80 in the test set, showing good performance in predicting IPA. CONCLUSION: Clinic, CT radiomics, and DL combined model could be used to predict IPA effectively.

CircMALAT1 promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma via the miR-512-5p/VCAM1 axis.

Circular RNAs play a pivotal role in the progression of various cancers. In our previous study, we observed high expression of the circRNA MALAT1 (cMALAT1) in intrahepatic cholangiocarcinoma (ICC) cells co-incubated with activated hepatic stellate cells. This study is designed to explore the roles of cMALAT1 and the underlying mechanisms in ICC. We find that cMALAT1 significantly facilitates the progression of ICC both in vitro and in vivo. The binding between cMALAT1 and miR-512-5p is subsequently confirmed through RNA pull-down experiments. As anticipated, the application of miR-512-5p mimics noticeably reverses the cMALAT1 overexpression-induced malignant phenotypes of ICC cells. Furthermore, VCAM1 is identified as a downstream gene of the cMALAT1/miR-512-5p axis. Importantly, silencing of VCAM1 not only effectively suppresses the malignant phenotypes of ICC cells but also significantly impairs the functions of cMALAT1. Our study reveals that cMALAT1 promotes the progression of ICC by competitively binding to VCAM1 mRNA with miR-512-5p, leading to the upregulation of VCAM1 expression and the activation of the PI3K/AKT signaling pathway.

Application of modified spiral tracheoplasty in thyroid carcinoma with trachea invasion: a retrospective analysis of 15 cases.

BACKGROUND: To describe the indications, techniques and preliminary experience of modified spiral tracheoplasty in the reconstruction of large tracheal defect after thyroidectomy. METHODS: The medical records of patients who underwent tracheal torsion to repair large tracheal defects after thyroid carcinoma surgery from January 2019 to January 2022 were retrospectively reviewed. The extent of tracheal defect, duration of tracheal reconstruction, postoperative complications and surgery results were analyzed. RESULTS: The duration of tracheal reconstruction was 30-60 min. No postoperative bleeding, incision infection, tracheostomy stenosis occurred. Recurrent laryngeal nerve palsy occurred in 5 patients. All patients were followed up for 24 to 60 months. The 2-year overall survival rate was 100%, the 2-year local control rate of trachea was 100%, and the 2-year tumor-free survival rate was 81.8%. CONCLUSION: The modified spiral tracheoplasty is a safe and effective method to repair the large defect of trachea after thyroid carcinoma invading the trachea.

Genome-Wide Profile of Mutations Induced by Carbon Ion Beam Irradiation of Dehulled Rice Seeds.

As a physical mutagen, carbon ion beam (CIB) irradiation can induce high-frequency mutation, which is user-friendly and environment-friendly in plant breeding. In this study, we resequenced eight mutant lines which were screened out from the progeny of the CIB-irradiated dehulled rice seeds. Among these mutants, CIB induced 135,535 variations, which include single base substitutions (SBSs), and small insertion and deletion (InDels). SBSs are the most abundant mutation, and account for 88% of all variations. Single base conversion is the main type of SBS, and the average ratio of transition and transversion is 1.29, and more than half of the InDels are short-segmented mutation (1-2 bp). A total of 69.2% of the SBSs and InDels induced by CIBs occurred in intergenic regions on the genome. Surprisingly, the average mutation frequency in our study is 9.8 × 10-5/bp and much higher than that of the previous studies, which may result from the relatively high irradiation dosage and the dehulling of seeds for irradiation. By analyzing the mutation of every 1 Mb in the genome of each mutant strain, we found some unusual high-frequency (HF) mutation regions, where SBSs and InDels colocalized. This study revealed the mutation mechanism of dehulled rice seeds by CIB irradiation on the genome level, which will enrich our understanding of the mutation mechanism of CIB radiation and improve mutagenesis efficiency.

Induction of zinc finger protein RNF6 auto-ubiquitination for the treatment of myeloma and chronic myeloid leukemia.

The zinc finger ubiquitin ligase RNF6 has been proposed as a potential therapeutic target in several cancers, but understanding its molecular mechanism of degradation has been elusive. In the present study, we find that RNF6 is degraded via auto-ubiquitination in a manner dependent on its Really Interesting New Gene (RING) domain. We determine that when the RING domain is deleted (ΔRING) or the core cysteine residues in the zinc finger are mutated (C632S/C635S), the WT protein, but not the ΔRING or mutant RNF6 protein, undergoes polyubiquitination. We also identify USP7 as a deubiquitinase of RNF6 by tandem mass spectrometry. We show that USP7 interacts with RNF6 and abolishes its K48-linked polyubiquitination, thereby preventing its degradation. In contrast, we found a USP7-specific inhibitor promotes RNF6 polyubiquitination, degradation, and cell death. Furthermore, we demonstrate the anti-leukemic drug Nilotinib and anti-myeloma drug Panobinostat (LBH589) induce RNF6 K48-linked polyubiquitination and degradation in both multiple myeloma (MM) and leukemia cells. In agreement with our hypothesis on the mode of RNF6 degradation, we show these drugs promote RNF6 auto-ubiquitination in an in vitro ubiquitination system without other E3 ligases. Consistently, reexpression of RNF6 ablates drug-induced MM and leukemia cell apoptosis. Therefore, our results reveal that RNF6 is a RING E3 ligase that undergoes auto-ubiquitination, which could be abolished by USP7 and induced by anti-cancer drugs. We propose that chemical induction of RNF6 auto-ubiquitination and degradation could be a novel strategy for the treatment of hematological malignancies including MM and leukemia.

Review of Design Routines of MXene Materials for Magnesium-Ion Energy Storage Device.

Renewable energy storage using electrochemical storage devices is extensively used in various field applications. High-power density supercapacitors and high-energy density rechargeable batteries are some of the most effective devices, while lithium-ion batteries (LIBs) are the most common. Due to the scarcity of Li resources and serious safety concerns during the construction of LIBs, development of safer and cheaper technologies with high performance is warranted. Magnesium is one of the most abundant and replaceable elements on earth, and it is safe as it does not generate dendrite following cycling. However, the lack of suitable electrode materials remains a critical issue in developing electrochemical energy storage devices. 2D MXenes can be used to construct composites with different dimensions, owing to their suitable physicochemical properties and unique magnesium-ion adsorption structure. In this study, the construction strategies of MXene in different dimensions, including its physicochemical properties as an electrode material in magnesium ion energy storage devices are reviewed. Research advancements of MXene and MXene-based composites in various kinds of magnesium-ion storage devices are also analyzed to understand its energy storage mechanisms. Finally, current opportunities, challenges, and future prospects are also briefly discussed to provide crucial information for future research.

Rapid identification of carbapenem-resistant Klebsiella pneumoniae based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry and an artificial neural network model.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a clinically critical pathogen that causes severe infection. Due to improper antibiotic administration, the prevalence of CRKP infection has been increasing considerably. In recent years, the utilization of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has enabled the identification of bacterial isolates at the families and species level. Moreover, machine learning (ML) classifiers based on MALDI-TOF MS have been recently considered a novel method to detect clinical antimicrobial-resistant pathogens. METHODS: A total of 2683 isolates (369 CRKP cases and 2314 carbapenem-susceptible Klebsiella pneumoniae [CSKP]) collected in the clinical laboratories of Taipei Medical University Hospital (TMUH) were included in this study, and 80% of data was split into the training data set that were submitted for the ML model. The remaining 20% of data was used as the independent data set for external validation. In this study, we established an artificial neural network (ANN) model to analyze all potential peaks on mass spectrum simultaneously. RESULTS: Our artificial neural network model for detecting CRKP isolates showed the best performance of area under the receiver operating characteristic curve (AUROC = 0.91) and of area under precision-recall curve (AUPRC = 0.90). Furthermore, we proposed the top 15 potential biomarkers in probable CRKP isolates at 2480, 4967, 12,362, 12,506, 12,855, 14,790, 15,730, 16,176, 16,218, 16,758, 16,919, 17,091, 18,142, 18,998, and 19,095 Da. CONCLUSIONS: Compared with the prior MALDI-TOF and machine learning studies of CRKP, the amount of data in our study was more sufficient and allowing us to conduct external validation. With better generalization abilities, our artificial neural network model can serve as a reliable screening tool for CRKP isolates in clinical practice. Integrating our model into the current workflow of clinical laboratories can assist the rapid identification of CRKP before the completion of traditional antimicrobial susceptibility testing. The combination of MADLI-TOF MS and machine learning techniques can support physicians in selecting suitable antibiotics, which has the potential to enhance the patients' outcomes and lower the prevalence of antimicrobial resistance.

Circ_0090231 knockdown protects vascular smooth muscle cells from ox-LDL-induced proliferation, migration and invasion via miR-942-5p/PPM1B axis during atherosclerosis.

Atherosclerosis (AS) is a dominant pathological basis of cardiovascular disease. Circular RNAs (circRNAs) have been proposed to have crucial functions in regulating pathological progressions of AS. Hence, the aim of this study was to investigate the potential function of circ_0090231 in AS progression. Oxidized low densitylipoprotein (ox-LDL)-challenged vascular smooth muscle cells (VSMCs) were used for in vitro functional analysis. Levels of genes and proteins were measured by qRT-PCR and Western blot. The proliferation, migration and invasion were assessed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell assays. The interaction between miR-942-5p and circ_0090231 or PPM1B (Protein Phosphatase, Mg2+/Mn2+ Dependent 1B) was evaluated by dual-luciferase reporter and pull-down assays. Circ_0090231 is a stable circRNA, and was increased in the serum of AS patients and ox-LDL-challenged VSMCs. Functionally, silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs. Mechanistically, circ_0090231 directly targeted miR-942-5p, and PPM1B was a target of miR-942-5p. Besides, circ_0090231 sequestered miR-942-5p to release PPM1B expression, suggesting the circ_0090231/miR-942-5p/PPM1B axis. Further rescue experiments showed that miR-942-5p inhibition or ectopic overexpression of PPM1B dramatically attenuated the suppressing influences of circ_0090231 knockdown on VSMC proliferative, migratory and invasive abilities under ox-LDL treatment. Silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs via miR-942-5p/PPM1B axis, providing a theoretical basis for elucidating the mechanism of AS process.

Porphyrin/phthalocyanine-based porous organic polymers for pollutant removal and detection: Synthesis, mechanisms, and challenges.

The growing global concern about environmental threats due to environmental pollution requires the development of environmentally friendly and efficient removal/detection materials and methods. Porphyrin/phthalocyanine (Por/Pc) based porous organic polymers (POPs) as a newly emerging porous material are prepared through polymerizing building blocks with different structures. Benefiting from the high porosity, adjustable pore structure, and enzyme-like activities, the Por/Pc-POPs can be the ideal platform to study the removal and detection of pollutants. However, a systematic summary of their application in environmental treatment is still lacking to date. In this review, the development of various Por/Pc-POPs for pollutant removal and detection applications over the past decade was systematically addressed for the first time to offer valuable guidance on environmental remediation through the utilization of Por/Pc-POPs. This review is divided into two sections (pollutants removal and detection) focusing on Por/Pc-POPs for organic, inorganic, and gaseous pollutants adsorption, photodegradation, and chemosensing, respectively. The related removal and sensing mechanisms are also discussed, and the methods to improve removal and detection efficiency and selectivity are also summarized. For the future practical application of Por/Pc-POPs, this review provides the emerging research directions and their application possibility and challenges in the removal and detection of pollutants.

Mg ion implantation and post-annealing effect on the photoelectrical performance of a ß-Ga2O3 photodetector.

The effects of magnesium ion implantation and post-annealing on the photoelectric performance of a ß-G a 2 O 3-based vertical structural Schottky photodetector (PD) were thoroughly investigated. After implantation and post-annealing, the Schottky barrier height and bandgap of the G a 2 O 3 surface can be slightly increased, while the dark current is significantly reduced, and the light-to-dark current ratio is immensely improved. The PD exhibited a photo-to-dark current ratio of 1733, responsivity of 5.04 mA/W, and specific detectivity of 3.979×1011 Jones under -2.6V bias, and the rise and decay times are 0.157 were 0.048 s, respectively. The large left shift of the open-circuit voltage is feasibly explained by applying the thermionic-emission diffusion theory.

High-performance layer-structured Si/Ga2O3/CH3NH3PbI3 heterojunction photodetector based on a Ga2O3 buffer interlayer.

Organic-inorganic metal halide perovskite-based photodetectors (PDs) have attracted great attention because they exhibit extraordinary optoelectronic performances due to advantages such as a low trap-state density and large absorption coefficient. As a buffer layer, G a 2 O 3 can block electron hole recombination, passivate an Si surface, reduce trap density, and improve the ability of electron tunneling. Here, we demonstrate a trilayer hybrid structure (S i/G a 2 O 3/C H 3 N H 3 P b I 3) composed of an n-type silicon wafer, G a 2 O 3 interlayer, and C H 3 N H 3 P b I 3 thin film. The effect of different G a 2 O 3 layer thicknesses on the characteristics of a PD was studied, which shows that the responsivity first increases and then decreases with an increase in the G a 2 O 3 film thickness; the optimized G a 2 O 3 thickness is 300 nm. Additionally, the optimal responsivity, detectivity, and the rise and decay times are 7.2m A W -1, 7.448×1010 Jones, and 39 and 1.7 ms, respectively. This device has a better performance because G a 2 O 3 and perovskite have a matched energy level. We believe our work could provide a new way to fabricate high-performance optoelectronic devices.

Postmortem biochemical analysis of soluble ST2 in the pericardial fluid of patients with sudden cardiac death caused by ischemic heart disease: a pilot study.

Soluble growth stimulation expressed gene 2 protein (sST2) is a myocardial protein induced by biomechanical stress. sST2 is widely present in the serum of patients with heart failure and is recommended as an important indicator to predict adverse outcomes in these patients. However, no postmortem biochemical analysis of sST2 in forensic practice has been reported. The present pilot study aimed to investigate the expression of sST2 in the pericardial fluid of patients with sudden cardiac death (SCD) caused by ischemic heart disease (IHD). In addition, to explore the relationship of sST2 with CK-MB, cTnT, and NT-proBNP, which have been proven to be auxiliary biomarkers for the diagnosis of SCD, we analyzed CK-MB, cTnT, NT-proBNP, and sST2 levels in twenty-one pericardial fluid samples from the Center of Forensic Investigation, China Medical University, with a Roche cobas e 411 electrochemiluminescence automatic immunoassay system and ST2/IL-33R Valukine™ enzyme-linked immunosorbent assay kit. The levels of sST2 in the pericardial fluid of patients with SCD caused by IHD were significantly increased (P < 0.01) and positively correlated with CK-MB and NT-proBNP (P < 0.0001). Receiver operating characteristic curve analysis indicated that the combined measurement of sST2 and NT-proBNP has a higher diagnostic value for SCD caused by IHD than the measurement of either indicator alone. This study preliminarily demonstrated that sST2 in the pericardial fluid was significantly increased in patients with SCD caused by IHD and might be used as a novel auxiliary biomarker for postmortem diagnosis of SCD in forensic practice.

E2F family play important roles in tumorigenesis.

Tumors are serious threats to human health. The transcription factors are regarded as the potential targets for tumor treatment. As an important family of transcription factors, E2F family transcription factors (E2Fs) play vital roles in cell proliferation and regulation. However, the expression feature, gene functions, and molecular interactions of E2Fs in tumorigenesis are not clear. In this study, the transcriptome data, mutation data, and protein-protein interaction data of 10 high-incidence tumors in China from the TCGA database were integrated and analyzed to explore the expression, structure, function, mutation, and phylogenetic characteristics of E2Fs. The results showed that E2F1 and E2F7 were regularly upregulated in the tumor samples. Moreover, E2Fs participated in the regulation of the cell cycle, cell aging, and other signaling pathways. As an important regulator, E2F1 interacted with more proteins than other E2Fs. At the same time, the genetic mutation types of E2Fs varied in tumor type and patient sex, of which gene amplification accounts for the largest proportion. Phylogenetic analysis showed that E2Fs were conserved in 41 species, including fruit flies, nematodes, and humans. Meanwhile, E2Fs had a tendency for gene expansion during evolution. In conclusion, this study clarified the expression pattern, mutation characteristics, and evolutionary trend of E2Fs in high-incidence tumors in China, and suggested that E2F family transcription factors could be novel diagnostic markers for tumor diseases. Furthermore, this work can provide a theoretical basis for the development of anti-tumor-targeted drugs.