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1.
J Am Chem Soc ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38870424

RESUMO

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38868950

RESUMO

Objective: To investigate the epidemic factors of hemorrhagic fever with renal syndrome (HFRS) and compare the S and M gene sequences of hantavirus (HV) between rodents and the infected cases. Methods: Detailed epidemiological investigations were conducted on the cases' working and living areas. Captured rodents were classified by night trapping method, and their lungs and blood were collected for virus carriage detection after aseptic dissection. Viral S and M fragments of HV RNA were amplified and sequenced from positive samples of cases and mice, and their homology was analyzed. Results: After reconstruction, the geographic and living environment changed significantly, altering rodent behaviors. The industrial park, characterized by high population density, poor living conditions, and frequent contact of rodent (feces) and humans, had a high rodent density and HV virus infection ratio. Four workers infected with HV were positive for anti-HV immunoglobulin G (IgG) and IgM. Among the positive samples, HV RNA was detected in all two cases, and four Rattus norvegicus specimens were Seoul type HV S3 subtype. The virus had the closest relationship with Rod/2012/QHD/4/Gc (Hebei, China) and RuianRn180 (Zhejiang, China), with the 100% homology of M gene segment. The homology of viral S gene segment exhibited the closest relationship with the Jiangxi isolated JiangxiXinjianRn-09-2011, ranging from 99.6% to 99.8%. Conclusion: The HV sequencing showed a strong epidemiological relationship between the cases and host rodents. Improving living environmental health conditions, administering HFRS vaccine, and reducing rodent density and human-rodent contact can mitigate the risk of HFRS.

3.
BioData Min ; 17(1): 16, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890715

RESUMO

GPT-4, as the most advanced version of OpenAI's large language models, has attracted widespread attention, rapidly becoming an indispensable AI tool across various areas. This includes its exploration by scientists for diverse applications. Our study focused on assessing GPT-4's capabilities in generating text, tables, and diagrams for biomedical review papers. We also assessed the consistency in text generation by GPT-4, along with potential plagiarism issues when employing this model for the composition of scientific review papers. Based on the results, we suggest the development of enhanced functionalities in ChatGPT, aiming to meet the needs of the scientific community more effectively. This includes enhancements in uploaded document processing for reference materials, a deeper grasp of intricate biomedical concepts, more precise and efficient information distillation for table generation, and a further refined model specifically tailored for scientific diagram creation.

4.
Chem Soc Rev ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836324

RESUMO

Electrochemical energy conversion and storage are playing an increasingly important role in shaping the sustainable future. Differential electrochemical mass spectrometry (DEMS) offers an operando and cost-effective tool to monitor the evolution of gaseous/volatile intermediates and products during these processes. It can deliver potential-, time-, mass- and space-resolved signals which facilitate the understanding of reaction kinetics. In this review, we show the latest developments and applications of DEMS in various energy-related electrochemical reactions from three distinct perspectives. (I) What is DEMS addresses the working principles and key components of DEMS, highlighting the new and distinct instrumental configurations for different applications. (II) How to use DEMS tackles practical matters including the electrochemical test protocols, quantification of both potential and mass signals, and error analysis. (III) Where to apply DEMS is the focus of this review, dealing with concrete examples and unique values of DEMS studies in both energy conversion applications (CO2 reduction, water electrolysis, carbon corrosion, N-related catalysis, electrosynthesis, fuel cells, photo-electrocatalysis and beyond) and energy storage applications (Li-ion batteries and beyond, metal-air batteries, supercapacitors and flow batteries). The recent development of DEMS-hyphenated techniques and the outlook of the DEMS technique are discussed at the end. As DEMS celebrates its 40th anniversary in 2024, we hope this review can offer electrochemistry researchers a comprehensive understanding of the latest developments of DEMS and will inspire them to tackle emerging scientific questions using DEMS.

5.
Front Genet ; 15: 1400387, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812967

RESUMO

Background: Currently, an increasing body of research suggests that blood-based long non-coding RNAs (lncRNAs) could serve as biomarkers for diagnosing multiple sclerosis (MS). This meta-analysis evaluates the diagnostic capabilities of selected lncRNAs in distinguishing individuals with MS from healthy controls and in differentiating between the relapsing and remitting phases of the disease. Methods: We conducted comprehensive searches across seven databases in both Chinese and English to identify relevant studies, applying stringent inclusion and exclusion criteria. The quality of the selected references was rigorously assessed using the QUADAS-2 tool. The analysis involved calculating summarized sensitivity (SSEN), specificity (SSPE), positive likelihood ratio (SPLR), negative likelihood ratio (SNLR), and diagnostic odds ratio (DOR) with 95% confidence intervals (CIs). Accuracy was assessed using summary receiver operating characteristic (SROC) curves. Results: Thirteen high-quality studies were selected for inclusion in the meta-analysis. Our meta-analysis assessed the combined diagnostic performance of lncRNAs in distinguishing MS patients from healthy controls. We found a SSEN of 0.81 (95% CI: 0.74-0.87), SSPE of 0.84 (95% CI: 0.78-0.89), SPLR of 5.14 (95% CI: 3.63-7.28), SNLR of 0.22 (95% CI: 0.16-0.31), and DOR of 23.17 (95% CI: 14.07-38.17), with an AUC of 0.90 (95% CI: 0.87-0.92). For differentiating between relapsing and remitting MS, the results showed a SSEN of 0.79 (95% CI: 0.71-0.85), SSPE of 0.76 (95% CI: 0.64-0.85), SPLR of 3.34 (95% CI: 2.09-5.33), SNLR of 0.28 (95% CI: 0.19-0.40), and DOR of 12.09 (95% CI: 5.70-25.68), with an AUC of 0.84 (95% CI: 0.81-0.87). Conclusion: This analysis underscores the significant role of lncRNAs as biomarkers in MS diagnosis and differentiation between its relapsing and remitting forms.

6.
Mol Plant Pathol ; 25(5): e13462, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38695630

RESUMO

MicroRNAs (miRNAs) are widely involved in various biological processes of plants and contribute to plant resistance against various pathogens. In this study, upon sugarcane mosaic virus (SCMV) infection, the accumulation of maize (Zea mays) miR398b (ZmmiR398b) was significantly reduced in resistant inbred line Chang7-2, while it was increased in susceptible inbred line Mo17. Degradome sequencing analysis coupled with transient co-expression assays revealed that ZmmiR398b can target Cu/Zn-superoxidase dismutase2 (ZmCSD2), ZmCSD4, and ZmCSD9 in vivo, of which the expression levels were all upregulated by SCMV infection in Chang7-2 and Mo17. Moreover, overexpressing ZmmiR398b (OE398b) exhibited increased susceptibility to SCMV infection, probably by increasing reactive oxygen species (ROS) accumulation, which were consistent with ZmCSD2/4/9-silenced maize plants. By contrast, silencing ZmmiR398b (STTM398b) through short tandem target mimic (STTM) technology enhanced maize resistance to SCMV infection and decreased ROS levels. Interestingly, copper (Cu)-gradient hydroponic experiments demonstrated that Cu deficiency promoted SCMV infection while Cu sufficiency inhibited SCMV infection by regulating accumulations of ZmmiR398b and ZmCSD2/4/9 in maize. These results revealed that manipulating the ZmmiR398b-ZmCSD2/4/9-ROS module provides a prospective strategy for developing SCMV-tolerant maize varieties.


Assuntos
Resistência à Doença , MicroRNAs , Doenças das Plantas , Potyvirus , Zea mays , Zea mays/virologia , Zea mays/genética , Potyvirus/fisiologia , Potyvirus/patogenicidade , Doenças das Plantas/virologia , Doenças das Plantas/genética , Resistência à Doença/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Espécies Reativas de Oxigênio/metabolismo
7.
World J Surg Oncol ; 22(1): 133, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762741

RESUMO

BACKGROUND: Human endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions of HHLA2 in pancreatic cancer (PC) remain incompletely elucidated. METHODS: We initially conducted an analysis of the B7 family members' expression pattern in pancreatic tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR and western blot methods were used to assess HHLA2 expression levels in PC tissues and cell lines. Furthermore, after silencing HHLA2 in PC cell lines, cell migration and proliferation of PC cells were detected by wound healing and CCK-8 assays, and cell invasion of PC cells was detected by transwell assays. We also investigated the regulation of epithelial-mesenchymal transition (EMT) markers and levels of EGFR, MEK, ERK1/2, mTOR and AKT via western blot analysis. Finally, the correlation between HHLA2 expression and immune infiltration was further explored. RESULTS: Silencing of HHLA2 resulted in the inhibition of PC cell proliferation, migration and invasion, potentially through the suppression of the EGFR/MAPK/ERK and mTOR/AKT signaling pathway. Additionally, silencing HHLA2 led to the inhibition of M2-type polarization of tumor associated macrophages (TAMs). CONCLUSION: The knockdown of HHLA2 was observed to inhibit the migration and invasion of PC cells through the regulation of the EMT process and EGFR/MAPK/ERK and mTOR/AKT pathway. Furthermore, silencing HHLA2 was found to modulate M2 polarization of TAMs. These finding suggest that HHLA2 could be a promising therapeutic target for Pancreatic cancer.


Assuntos
Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Receptores ErbB , Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Serina-Treonina Quinases TOR/metabolismo , Receptores ErbB/metabolismo , Receptores ErbB/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Progressão da Doença , Prognóstico , Macrófagos/metabolismo , Macrófagos/patologia , Células Tumorais Cultivadas , Transdução de Sinais , Masculino , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Sistema de Sinalização das MAP Quinases , Apoptose , Células THP-1 , Regulação Neoplásica da Expressão Gênica , Feminino , Imunoglobulinas
8.
Int J Surg ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38788195

RESUMO

OBJECTIVE: Most bladder cancers are non-muscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach. METHODS: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias. RESULTS: This study included 118,477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 (P < 0.0001); RFS of 2.21 (P < 0.0001); SEER cohort OS HR of 1.10 (P = 0.0001); DSS HR of 1.13 (P = 0.0183). Dome tumors displayed similar trends (Chinese NMIBC cohort OS HR of 7.91 (P < 0.0001); RFS HR of 2.12 (P < 0.0001); SEER OS HR of 1.05 (P = 0.0087); DSS HR of 1.14 (P = 0.0006)). Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment (P < 0.01). CONCLUSION: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients.

9.
Opt Lett ; 49(10): 2617-2620, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748119

RESUMO

Fourier ptychographic microscopy (FPM) needs to realize well-accepted reconstruction by image segmentation and discarding problematic data due to artifacts caused by vignetting. However, the imaging results have long suffered from uneven color blocks and the consequent digital stitching artifacts, failing to bring satisfying experiences to researchers and users over the past decade since the invention of FPM. In fact, the fundamental reason for vignetting artifacts lies in that the acquired data does not match the adopted linear-space-invariant (LSI) forward model, i.e., the actual object function is modulated by a quadratic phase factor during data acquisition, which has been neglected in the advancement of FPM. In this Letter, we rederive a linear-space-variant (LSV) model for FPM and design the corresponding loss function for FPM, termed LSV-FPM. Utilizing LSV-FPM for optimization enables the efficient removal of wrinkle artifacts caused by vignetting in the reconstruction results, without the need of segmenting or discarding images. The effectiveness of LSV-FPM is validated through data acquired in both 4f and finite conjugate single-lens systems.

10.
Front Oncol ; 14: 1324181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699643

RESUMO

Background: The current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC. Methods: We retrospectively analyzed 82 patients diagnosed with mHSPC, including 18 patients treated with abiraterone acetate with prednisone, 21 patients with enzalutamide, 20 patients with apalutamide, and 23 patients with bicalutamide. We evaluated PSA progression-free survival (PSA-PFS), imaging progression-free survival (r PFS), castration resistance progression-free survival (CRPC-PFS), and overall survival (OS) using Kaplan-Meier survival analyses. Additionally, we explored relevant factors affecting prognosis through univariate and multivariate Cox risk-proportionality models. PSA response rates at 3, 6, and 12 months, nadir PSA levels (nPSA), and time to nadir (TTN) in different medication subgroups after treatment were documented, and we used one-way ANOVA to determine the effect of these measures on patient prognosis. Results: In comparison with bicalutamide, both enzalutamide and apalutamide have shown significant advantages in delaying disease progression among mHSPC patients. Specifically, enzalutamide has been found to significantly prolong PSA-PFS (HR 2.244; 95% CI 1.366-3.685, p=0.001), rPFS (HR 2.539; 95% CI 1.181-5.461; p= 0.007), CRPC-PFS (HR 2.131; 95% CI 1.295-3.506; p= 0.003), and OS (HR 2.06; 95% CI 1.183-3.585; P=0.005). Similarly, apalutamide has significantly extended PSA-PFS (HR 5.071; 95% CI 1.711-15.032; P= 0.003) and CRPC-PFS (HR 6.724; 95% CI 1.976-22.878; P=0.002) among patients. On the other hand, the use of abiraterone in combination with ADT did not demonstrate a significant advantage in delaying diseases progression when compared with the other three agents in mHSPC patients. There were no significant differences in overall adverse event rates among the four pharmaceuticals in terms of safety. Additionally, the observation of PSA kinetics revealed that enzalutamide, apalutamide, and abiraterone acetate had a significant advantage in achieving deep PSA response (PSA ≤ 0.2 ng/ml) compared with bicalutamide (p=0.007 at 12 months). Enzalutamide and apalutamide exhibited preeminence efficacy, with no substantial difference observed between the two medications. Conclusions: Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than bicalutamide. Furthermore, enzalutamide and apalutamide were found to significantly prolong survival and delay disease progression in mHSPC patients compared with bicalutamide. It should be noted that abiraterone did not demonstrate a significant advantage in delaying disease compared with enzalutamide and apalutamide. After conducting drug toxicity analyses, it was determined that there were no significant differences among the four drugs.

11.
Pestic Biochem Physiol ; 201: 105893, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685255

RESUMO

Potato virus Y (PVY) is one of the most important pathogens in the genus Potyvirus that seriously harms agricultural production. Copper (Cu), as a micronutrient, is closely related to plant immune response. In this study, we found that foliar application of Cu could inhibit PVY infection to some extent, especially at 7 days post inoculation (dpi). To explore the effect of Cu on PVY infection, transcriptome sequencing analysis was performed on PVY-infected tobacco with or without Cu application. Several key pathways regulated by Cu were identified, including plant-pathogen interaction, inorganic ion transport and metabolism, and photosynthesis. Moreover, the results of virus-induced gene silencing (VIGS) assays revealed that NbMLP423, NbPIP2, NbFd and NbEXPA played positive roles in resistance to PVY infection in Nicotiana benthamiana. In addition, transgenic tobacco plants overexpressing NtEXPA11 showed increased resistance to PVY infection. These results contribute to clarify the role and regulatory mechanism of Cu against PVY infection, and provide candidate genes for disease resistance breeding.


Assuntos
Cobre , Resistência à Doença , Nicotiana , Doenças das Plantas , Potyvirus , Nicotiana/virologia , Nicotiana/genética , Potyvirus/fisiologia , Cobre/farmacologia , Doenças das Plantas/virologia , Resistência à Doença/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica , Plantas Geneticamente Modificadas/virologia , Regulação da Expressão Gênica de Plantas , Transcriptoma
12.
Int Immunopharmacol ; 132: 111940, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38593503

RESUMO

Glutathione metabolism (GM) is a crucial part of various metabolic and pathophysiological processes. However, its role in lung adenocarcinoma (LUAD) has not been comprehensively studied. This study aimed to explore the potential relationship between GM genes, the prognosis, and the immune microenvironment of patients with LUAD. We constructed a risk signature model containing seven GM genes using Lasso combined Cox regression and validated it using six GEO datasets. Our analysis showed that it is an independent prognostic factor. Functional enrichment analysis revealed that the GM genes were significantly enriched in cell proliferation, cell cycle regulation, and metabolic pathways. Clinical and gene expression data of patients with LUAD were obtained from the TCGA database and patients were divided into high- and low-risk groups. The high-risk patient group had a poor prognosis, reduced immune cell infiltration, poor response to immunotherapy, high sensitivity to chemotherapy, and low sensitivity to targeted therapy. Subsequently, single-cell transcriptome analysis using the GSE143423 and GSE127465 datasets revealed that the core SMS gene was highly enriched in M2 Macrophages. Finally, nine GEO datasets and multiple fluorescence staining revealed a correlation between the SMS expression and M2 macrophage polarization. Our prognostic model in which the core SMS gene is closely related to M2 macrophage polarization is expected to become a novel target and strategy for tumor therapy.


Assuntos
Adenocarcinoma de Pulmão , Regulação Neoplásica da Expressão Gênica , Glutationa , Neoplasias Pulmonares , Macrófagos , Microambiente Tumoral , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/mortalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Glutationa/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Bases de Dados Genéticas , Ativação de Macrófagos/genética , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Feminino
13.
Int J Biol Macromol ; 268(Pt 1): 131628, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38631577

RESUMO

MicroRNAs (miRNAs) play important roles in plant defense against various pathogens. ε-poly-l-lysine (ε-PL), a natural anti-microbial peptide produced by microorganisms, effectively suppresses tobacco mosaic virus (TMV) infection. To investigate the anti-viral mechanism of ε-PL, the expression profiles of miRNAs in TMV-infected Nicotiana tabacum after ε-PL treatment were analyzed. The results showed that the expression levels of 328 miRNAs were significantly altered by ε-PL. Degradome sequencing was used to identify their target genes. Integrative analysis of miRNAs target genes and gene-enriched GO/KEGG pathways indicated that ε-PL regulates the expression of miRNAs involved in critical pathways of plant hormone signal transduction, host defense response, and plant pathogen interaction. Subsequently, virus induced gene silencing combined with the short tandem targets mimic technology was used to analyze the function of these miRNAs and their target genes. The results indicated that silencing miR319 and miR164 reduced TMV accumulation in N. benthamiana, indicating the essential roles of these miRNAs and their target genes during ε-PL-mediated anti-viral responses. Collectively, this study reveals that microbial source metabolites can inhibit plant viruses by regulating crucial host miRNAs and further elucidate anti-viral mechanisms of ε-PL.


Assuntos
Regulação da Expressão Gênica de Plantas , MicroRNAs , Nicotiana , Polilisina , Vírus do Mosaico do Tabaco , Nicotiana/genética , Nicotiana/virologia , MicroRNAs/genética , MicroRNAs/metabolismo , Polilisina/farmacologia , Transcriptoma , Doenças das Plantas/virologia , Doenças das Plantas/genética , Antivirais/farmacologia , Perfilação da Expressão Gênica
14.
Cell Death Dis ; 15(4): 278, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637559

RESUMO

Myelodysplastic syndromes (MDS) are a heterogeneous group of pre-leukemic hematopoietic disorders characterized by cytopenia in peripheral blood due to ineffective hematopoiesis and normo- or hypercellularity and morphologic dysplasia in bone marrow (BM). An inflammatory BM microenvironment and programmed cell death of hematopoietic stem/progenitor cells (HSPCs) are thought to be the major causes of ineffective hematopoiesis in MDS. Pyroptosis, apoptosis and necroptosis (collectively, PANoptosis) are observed in BM tissues of MDS patients, suggesting an important role of PANoptosis in MDS pathogenesis. Caspase 8 (Casp8) is a master regulator of PANoptosis, which is downregulated in HSPCs from most MDS patients and abnormally spliced in HSPCs from MDS patients with SRSF2 mutation. To study the role of PANoptosis in hematopoiesis, we generated inducible Casp8 knockout mice (Casp8-/-). Mx1-Cre-Casp8-/- mice died of BM failure within 10 days of polyI:C injections due to depletion of HSPCs. Rosa-ERT2Cre-Casp8-/- mice are healthy without significant changes in BM hematopoiesis within the first 1.5 months after Casp8 deletion. Such mice developed BM failure upon infection or low dose polyI:C/LPS injections due to the hypersensitivity of Casp8-/- HSPCs to infection or inflammation-induced necroptosis which can be prevented by Ripk3 deletion. However, impaired self-renewal capacity of Casp8-/- HSPCs cannot be rescued by Ripk3 deletion due to activation of Ripk1-Tbk1 signaling. Most importantly, mice transplanted with Casp8-/- BM cells developed MDS-like disease within 4 months of transplantation as demonstrated by anemia, thrombocytopenia and myelodysplasia. Our study suggests an essential role for a balance in Casp8, Ripk3-Mlkl and Ripk1-Tbk1 activities in the regulation of survival and self-renewal of HSPCs, the disruption of which induces inflammation and BM failure, resulting in MDS-like disease.


Assuntos
Síndromes Mielodisplásicas , Animais , Humanos , Camundongos , Transtornos da Insuficiência da Medula Óssea/complicações , Caspase 8/genética , Caspase 8/metabolismo , Inflamação/metabolismo , Camundongos Knockout , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo
15.
Membranes (Basel) ; 14(4)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38668101

RESUMO

The high concentration of chloride ions in desulphurization wastewater is the primary limiting factor for its reusability. Monovalent anion selective electrodialysis (S-ED) enables the selective removal of chloride ions, thereby facilitating the reuse of desulfurization wastewater. In this study, different concentrations of NaCl and Na2SO4 were used to simulate different softened desulfurization wastewater. The effects of current density and NaCl and Na2SO4 concentration on ion flux, permselectivity (PSO42-Cl-) and specific energy consumption were studied. The results show that Selemion ASA membrane exhibits excellent permselectivity for Cl- and SO42-, with a significantly lower flux observed for SO42- compared to Cl-. Current density exerts a significant influence on ion flux; as the current density increases, the flux of SO42- also increases but at a lower rate than that of Cl-, resulting in an increase in permselectivity. When the current density reaches 25 mA/cm2, the permselectivity reaches a maximum of 50.4. The increase in NaCl concentration leads to a decrease in the SO42- flux; however, the permselectivity is reduced due to the elevated Cl-/SO42- ratio. The SO42- flux increases with the increase in Na2SO4 concentration, while the permselectivity increases with the decrease in Cl-/SO42- ratio.

16.
Sci Technol Adv Mater ; 25(1): 2336399, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628978

RESUMO

Photovoltaic-thermoelectric (PV-TE) tandem system has been considered as an effective way to fully utilize the solar spectrum, and has been demonstrated in a perovskite solar cell (PSC)-thermoelectric (TE) configuration. However, the conventional PSC-TE tandem architecture cannot convert infrared light transmitted through the upper PSC into heat effectively, impeding the heat-electricity conversion of TE devices. Herein, a semi-transparent PSC-photothermal-TE tandem system is designed for improved photothermal utilization. Through optimizing the buffer layer of the back transparent electrode, semi-transparent PSC with a power conversion efficiency (PCE) of 13% and an average transmittance of 53% in the range of 800-1500 nm was obtained. On this basis, a photothermal thin film was introduced between the semi-transparent PSC and the TE device, which increased the efficiency contribution ratio of the TE device from 14% to 19%, showing enhanced utilization of AM 1.5 G solar spectrum and improved photo-thermal-electric conversion efficiency.


We have constructed a semi-transparent perovskite solar cell-photothermal-thermoelectric tandem system through the optimization of transparent back electrode and the introduction of photothermal thin-film, realizing enhanced utilization of solar energy.

17.
J Med Internet Res ; 26: e46777, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635981

RESUMO

BACKGROUND: As global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture relationships central to the disease's etiology and response to drugs. OBJECTIVE: We designed the Alzheimer's Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics. METHODS: We designed the AlzKB as a large, heterogeneous graph knowledge base assembled using 22 diverse external data sources describing biological and pharmaceutical entities at different levels of organization (eg, chemicals, genes, anatomy, and diseases). AlzKB uses a Web Ontology Language 2 ontology to enforce semantic consistency and allow for ontological inference. We provide a public version of AlzKB and allow users to run and modify local versions of the knowledge base. RESULTS: AlzKB is freely available on the web and currently contains 118,902 entities with 1,309,527 relationships between those entities. To demonstrate its value, we used graph data science and machine learning to (1) propose new therapeutic targets based on similarities of AD to Parkinson disease and (2) repurpose existing drugs that may treat AD. For each use case, AlzKB recovers known therapeutic associations while proposing biologically plausible new ones. CONCLUSIONS: AlzKB is a new, publicly available knowledge resource that enables researchers to discover complex translational associations for AD drug discovery. Through 2 use cases, we show that it is a valuable tool for proposing novel therapeutic hypotheses based on public biomedical knowledge.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Reconhecimento Automatizado de Padrão , Bases de Conhecimento , Aprendizado de Máquina , Conhecimento
18.
Front Oncol ; 14: 1355454, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482208

RESUMO

Background and aims: With the rapid growth of artificial intelligence (AI) applications in various fields, understanding its impact on liver cancer research is paramount. This scientometrics project aims to investigate publication trends and topics in AI-related publications in liver cancer. Materials and Methods: We employed a search strategy to identify AI-related publications in liver cancer using Scopus database. We analyzed the number of publications, author affiliations, and journals that publish AI-related publications in liver cancer. Finally, the publications were grouped based on intended application. Results: We identified 3950 eligible publications (2695 articles, 366 reviews, and 889 other document types) from 1968 to August 3, 2023. There was a 12.7-fold increase in AI-related publications from 2013 to 2022. By comparison, the number of total publications on liver cancer increased by 1.7-fold. Our analysis revealed a significant shift in trends of AI-related publications on liver cancer in 2019. We also found a statistically significant consistent increase in numbers of AI-related publications over time (tau = 0.756, p < 0.0001). Eight (53%) of the top 15 journals with the most publications were radiology journals. The largest number of publications were from China (n=1156), the US (n=719), and Germany (n=236). The three most common publication categories were "medical image analysis for diagnosis" (37%), "diagnostic or prognostic biomarkers modeling & bioinformatics" (19%), and "genomic or molecular analysis" (18%). Conclusion: Our study reveals increasing interest in AI for liver cancer research, evidenced by a 12.7-fold growth in related publications over the past decade. A common application of AI is in medical imaging analysis for various purposes. China, the US, and Germany are leading contributors.

19.
BMC Psychiatry ; 24(1): 210, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500067

RESUMO

BACKGROUND: Current research has been focusing on non-suicidal self-injury (NSSI) behaviors among adolescents with depression. Although family intimacy and adaptability are considered protective factors for NSSI, evidence supporting this relationship is lacking. OBJECTIVE: This study aims to examine the mechanisms operating in the relationship between family intimacy and adaptability and NSSI behaviors among adolescents. METHODS: A self-administered general demographic information questionnaire, the Behavioral Functional Assessment Scale for Non-Suicidal Self-Injury, the Family Intimacy and Adaptability Scale, the Connor-Davidson Resilience Scale, and the Self-Assessment of Depression Scale were distributed among adolescents with depression in three tertiary hospitals in Jiangsu Province. RESULTS: The relationship between family intimacy and adaptability and NSSI was assessed among 596 adolescents with depression. The results revealed the following: (1) Family intimacy and adaptability were negatively correlated with NSSI behavior. (2) Psychological resilience and depression levels acted as chain mediators in the relationship between family intimacy and adaptability and NSSI behavior. CONCLUSIONS: Enhancing psychological resilience, controlling depressive symptoms, and reducing depression severity among adolescents by improving their family intimacy and adaptability are conducive to preventing and mitigating their NSSI behaviors.


Assuntos
Resiliência Psicológica , Comportamento Autodestrutivo , Adolescente , Humanos , Análise de Mediação , Comportamento Autodestrutivo/psicologia , Testes Psicológicos
20.
Artigo em Inglês | MEDLINE | ID: mdl-38548696

RESUMO

INTRODUCTION: The optimal management of blunt thoracic aortic injury (BTAI) remains controversial, with experienced centers offering therapy ranging from medical management to TEVAR. We investigated the utility of a machine learning (ML) algorithm to develop a prognostic model of risk factors on mortality in patients with BTAI. METHODS: The Aortic Trauma Foundation registry was utilized to examine demographics, injury characteristics, management and outcomes of patients with BTAI. A STREAMLINE (A Simple, Transparent, End-To-End Automated Machine Learning Pipeline Facilitating Data Analysis and Algorithm Comparison) model as well as logistic regression (LR) analysis with imputation using chained equations was developed and compared. RESULTS: From a total of 1018 patients in the registry, 702 patients were included in the final analysis. Of the 258 (37%) patients who were medically managed, 44 (17%) died during admission, 14 (5.4%) of which were aortic related deaths. 444 (63%) patients underwent TEVAR and 343 of which underwent TEVAR within 24 hours of admission. Amongst TEVAR patients, 39 (8.8%) patients died and 7 (1.6%) had aortic related deaths. (Table 1) Comparison of the STREAMLINE and LR model showed no significant difference in ROC curves and high AUCs of 0.869 (95% CI, 0.813 - 0.925) and 0.840 (95% CI, 0.779 - 0.900) respectively in predicting in-hospital mortality. Unexpectedly, however, the variables prioritized in each model differed between models (Figure 1A-B). The top three variables identified from the LR model were similar to that from existing literature. The STREAMLINE model, however, prioritized location of the injury along the lesser curve, age and aortic injury grade (Figure 1A). CONCLUSIONS: Machine learning provides insight on prioritization of variables not typically identified in standard multivariable logistic regression. Further investigation and validation in other aortic injury cohorts are needed to delineate the utility of ML models. LEVEL OF EVIDENCE: Level IIIStudy TypeOriginal research (prognostic/epidemiological).

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