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1.
Artigo em Inglês | MEDLINE | ID: mdl-38917287

RESUMO

More than 6 million Americans are at risk for Alzheimer's Disease Related Dementias (ADRD), most of whom are 65 or older. The clock drawing test (CDT) is a quick, simple, and effective technique that has the potential advantage of self-management and screening for ADRD patients. Current CDT-based ADRD screening studies focus more on efficacy, involving many handcrafted features, ignoring data modalities, and lacking validation. This paper aims to propose a unified telemedicine framework for fully and semi-automatic effective early ADRD screening based on multimodal and agile data fusion, focusing on the interpretability and validation of the model by using gradient-weighted class activation mapping (Grad-CAM) and locally linear embedding (LLE). The datasets for this work include 1,662 samples of CDT images and related demographic and cognitive information. The fully automatic case involving only CDT images can achieve the highest AUC of 81% with a 75% recall rate in binary screening. The multimodal data fusion in the semi-automatic case can achieve up to 90% AUC with an 83% recall rate. The visualization of the Convolutional Neural Networks (CNN) shows that it can automatically obtain critical information about the outline, scale, and clock hands from CDT images, and the analysis of structured features shows that the memory test is key to effective ADRD screening.

2.
Ecotoxicol Environ Saf ; 281: 116563, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38878560

RESUMO

Evodiamine (EVO), the main active alkaloid in Evodia rutaecarpa, was shown to exert various pharmacological activities, especially anti-tumor. Currently, it is considered a potential anti-cancer drug due to its excellent anti-tumor activity, which unfortunately has adverse reactions, such as the risk of liver and kidney injury, when Evodia rutaecarpa containing EVO is used clinically. In the present study, we aim to clarify the potential toxic target organs and toxicity mechanism of EVO, an active monomer in Evodia rutaecarpa, and to develop mitigation strategies for its toxicity mechanism. Transcriptome analysis and related experiments showed that the PI3K/Akt pathway induced by calcium overload was an important step in EVO-induced apoptosis of renal cells. Specifically, intracellular calcium ions were increased, and mitochondrial calcium ions were decreased. In addition, EVO-induced calcium overload was associated with TRPV1 receptor activation. In vivo TRPV1 antagonist and calcium chelator effects were observed to significantly reduce body weight loss and renal damage in mice due to EVO toxicity. The potential nephrotoxicity of EVO was further confirmed by an in vivo test. In conclusion, TRPV1-mediated calcium overload-induced apoptosis is one of the mechanisms contributing to the nephrotoxicity of EVO due to its toxicity, whereas maintaining body calcium homeostasis is an effective measure to reduce toxicity. These studies suggest that the clinical use of EVO-containing herbal medicines should pay due attention to the changes in renal function of patients as well as the off-target effects of the drugs.


Assuntos
Apoptose , Cálcio , Evodia , Homeostase , Rim , Quinazolinas , Quinazolinas/toxicidade , Quinazolinas/farmacologia , Animais , Homeostase/efeitos dos fármacos , Cálcio/metabolismo , Camundongos , Apoptose/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Evodia/química , Masculino , Canais de Cátion TRPV/metabolismo , Quelantes de Cálcio/farmacologia
3.
Polymers (Basel) ; 16(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38931994

RESUMO

Two new triarylamine-based diamine monomers, namely, N,N'-bis(4-methoxyphenyl)-N,N'-bis(4-(4-aminophenyl-4'-methoxyphenylamino)phenyl)-p-phenylenediamine (3) and N,N'-bis(4-methoxyphenyl)-N,N'-bis(4-((4-aminophenyl-1-naphthyl)amino)phenyl)-p-phenylenediamine (7), were successfully synthesized and led to two series of electroactive polyamides by polycondensation reactions with common aromatic dicarboxylic acids. The polymers demonstrated multicolored electrochromism, high optical contrast, and remarkable enhancements in redox and electrochromic stability. Compared to other triarylamine-based polymers, the studied polyamides exhibited enhanced electrochromic stability (only 3~6% decay of its coloration efficiency at 445 nm after 14,000 switching cycles) at the first oxidation stage. The polyamides also showed strong absorption in the near-infrared region upon oxidation. Polymers with multicolored electrochromism and high redox stability can be developed by incorporation of four triarylamine cores in each repeat unit and electron-donating methoxy groups on the active sites of the triphenylamine units.

4.
J Org Chem ; 89(12): 9031-9042, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38829824

RESUMO

A cooperative Rh/achiral phosphoric acid-enabled [3+3] cycloaddition of in situ-generated carbonyl ylides with quinone monoimines has been developed. With the ability to build up the molecular complexity rapidly and efficiently, this method furnishes highly functionalized oxa-bridged benzofused dioxabicyclo[3.2.1]octane scaffolds bearing two quaternary centers in good to excellent yields under mild conditions. Moreover, the utility of the current method was demonstrated by gram-scale synthesis and elaboration of the products into various functionalized oxa-bridged heterocycles.

5.
Neoplasia ; 55: 101012, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38875930

RESUMO

Increased mutational burden and EBV load have been revealed from normal tissues to Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs). BPLF1, encoded by EBV, is a lytic cycle protein with deubiquitinating activity has been found to participate in disrupting repair of DNA damage. We first confirmed that BPLF1 gene in gastric cancer (GC) significantly increased the DNA double strand breaks (DSBs). Ubiquitination mass spectrometry identified histones as BPLF1 interactors and potential substrates, and co-immunoprecipitation and in vitro experiments verified that BPLF1 regulates H2Bub by targeting Rad6. Over-expressing Rad6 restored H2Bub but partially reduced γ-H2AX, suggesting that other downstream DNA repair processes were affected. mRNA expression of BRCA2 were significantly down-regulated by next-generation sequencing after over-expression of BPLF1, and over-expression of p65 facilitated the repair of DSBs. We demonstrated BPLF1 may lead to the accumulation of DSBs by two pathways, reducing H2B ubiquitination (H2Bub) and blocking homologous recombination which may provide new ideas for the treatment of gastric cancer.


Assuntos
Quebras de DNA de Cadeia Dupla , Infecções por Vírus Epstein-Barr , Instabilidade Genômica , Herpesvirus Humano 4 , Histonas , Neoplasias Gástricas , Ubiquitinação , Humanos , Herpesvirus Humano 4/genética , Neoplasias Gástricas/virologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/etiologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Histonas/metabolismo , Linhagem Celular Tumoral , Reparo do DNA , Enzimas Desubiquitinantes/metabolismo , Enzimas Desubiquitinantes/genética , Regulação Neoplásica da Expressão Gênica , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Carcinogênese/genética , Proteínas Virais Reguladoras e Acessórias
6.
Phys Rev Lett ; 132(16): 160801, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38701444

RESUMO

A solid-state approach for quantum networks is advantageous, as it allows the integration of nanophotonics to enhance the photon emission and the utilization of weakly coupled nuclear spins for long-lived storage. Silicon carbide, specifically point defects within it, shows great promise in this regard due to the easy of availability and well-established nanofabrication techniques. Despite of remarkable progresses made, achieving spin-photon entanglement remains a crucial aspect to be realized. In this Letter, we experimentally generate entanglement between a silicon vacancy defect in silicon carbide and a scattered single photon in the zero-phonon line. The spin state is measured by detecting photons scattered in the phonon sideband. The photonic qubit is encoded in the time-bin degree of freedom and measured using an unbalanced Mach-Zehnder interferometer. Photonic correlations not only reveal the quality of the entanglement but also verify the deterministic nature of the entanglement creation process. By harnessing two pairs of such spin-photon entanglement, it becomes straightforward to entangle remote quantum nodes at long distance.

7.
Diabetes Metab Syndr Obes ; 17: 2085-2094, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799278

RESUMO

Background: Apolipoprotein (Apo) may be associated with sarcopenia in elderly inpatients with type 2 diabetes mellitus (T2DM), but fewer studies are available. In this study, we explored the association of ApoA1, ApoB, and ApoB/ApoA1 with sarcopenia and compared the predictive role of Apo indicators for sarcopenia in an elderly T2DM. Objective: To investigate the relationships between the Apo and sarcopenia in elderly inpatients with T2DM. Methods: This study included 253 inpatients with T2DM (mean age of 70.11±5.44 years, 32.8% male). The inpatients were divided into the sarcopenic group (n = 100) and non-sarcopenic group (n = 153). The associations among the Apo and sarcopenia were assessed using multivariate analyses. Results: Inpatients in the sarcopenia group showed lower ApoA1 levels than those in the non-sarcopenia group (1.25±0.21 vs 1.36±0.20 g/L, P < 0.05) and showed higher ApoB/ApoA1 and ApoB levels than those in the non-sarcopenia group (0.82±0.27 vs 0.69±0.19 g/L, P < 0.05;1.00±0.32 vs 0.93±0.24 g/L, P < 0.05, respectively). After adjusting for age and BMI, the logistic regression model indicated that ApoA1 was a protective factor for elderly inpatients with T2DM sarcopenia.(OR =0.079,95% CI: 0.021~0.306, P < 0.05);ApoB and AopB/AopA1 were risk factors for elderly inpatients with T2DM sarcopenia.(OR =3.578,95% CI:1.318~9.715, P < 0.05;OR =16.440,95% CI:4.437~60.427, P < 0.05, respectively). AopB/AopA1 provided an AUC value of 0.765 in elderly men.(95% CI: 0.665~0.866, P<0.05). Conclusion: ApoA1, AopB, and AopB/AopA1 are associated with sarcopenia in elderly inpatients with T2DM, and AopB/AopA1 may be a potential predictor of sarcopenia in elderly men with T2DM.

8.
Ther Adv Infect Dis ; 11: 20499361241248058, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681967

RESUMO

Background: Urosepsis is a common disease in urology, which is characterized by high treatment costs and high mortality. In the treatment of sepsis, anti-infection therapy is the most important means. However, the effect of empirical anti-infection therapy is often not ideal. Therefore, it is necessary to continuously monitor the prevalence of bacterial isolates in the blood culture of patients with urinary sepsis and their sensitivity to antibacterial drugs. This is of great significance to improve the efficacy of empirical antibiotic therapy for urosepsis. Objective: To elucidate the landscape of prevailing bacterial profiles and their antimicrobial susceptibilities in urosepsis cases, and to furnish robust clinical evidence to underpin the timely initiation of empirical antibiotic treatment. Methods: Collect the basic information and blood culture results of patients with urosepsis hospitalized from 2017 to 2020. Retrospective analysis of bacterial species and antimicrobial susceptibility in urosepsis and changes over 4 years. Results: Gram-negative bacteria (178 isolates, 75.11%) constituted the main pathogens causing urosepsis, followed by Gram-positive bacteria (46 isolates, 19.41%) and fungus (13 isolates, 5.48%). The sensitivity of ertapenem, meropenem, amikacin, and imipenem to Gram-negative bacteria all exceeded 85%. The sensitivity rates of levofloxacin, gentamicin, and ciprofloxacin are decreasing every year (p < 0.05). Tigecycline, vancomycin, and linezolid exhibited excellent sensitivity against Gram-positive bacteria. Among fungi, fluconazole demonstrated universal sensitivity, while itraconazole-resistant isolates have been found, and amphotericin B is still effective. Conclusion: Analysis of blood culture results of patients more accurately reflected the etiology of urosepsis, mainly Escherichia coli, Enterococcus, and Klebsiella pneumoniae. If there are no definitive blood culture results, empiric treatment of urosepsis should not include fluoroquinolone antibiotics. Cefepime, cefoxitin, and ceftazidime are the most sensitive antibiotics to Gram-negative bacteria besides carbapenem antibiotics. In addition, the current situation regarding extended-spectrum ß-lactamase-producing bacteria and carbapenem-resistant Enterobacteriaceae bacteria resistance is extremely concerning with limited therapeutic options available. Strengthening antibiotic management practices and exploring novel antibacterial agents can help mitigate this issue.

9.
Small Methods ; : e2301633, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682581

RESUMO

Metal halide perovskites emerge as promising semiconductors for optoelectronic devices due to ease of fabrication, attractive photophysical properties, their low cost, highly tunable material properties, and high performance. High-quality thin films of metal halide perovskites are the basis of most of these applications including solar cells, light-emitting diodes, photodetectors, and electronic memristors. A typical fabrication method for perovskite thin films is the solution method, which has several limitations in device reproducibility, adverse environmental impact, and utilization of raw materials. Thermal evaporation holds great promise in addressing these bottlenecks in fabricating high-quality halide perovskite thin films. It also has high compatibility with mass-production platforms that are well-established in industries. This review first introduces the basics of the thermal evaporation method with a particular focus on the critical parameters influencing the thin film deposition. The research progress of the fabrication of metal halide perovskite thin films is further summarized by different thermal evaporation approaches and their applications in solar cells and other optoelectronic devices. Finally, research challenges and future opportunities for both fundamental research and commercialization are discussed.

10.
IEEE J Biomed Health Inform ; 28(7): 4281-4294, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38557614

RESUMO

As post-transcriptional regulators of gene expression, micro-ribonucleic acids (miRNAs) are regarded as potential biomarkers for a variety of diseases. Hence, the prediction of miRNA-disease associations (MDAs) is of great significance for an in-depth understanding of disease pathogenesis and progression. Existing prediction models are mainly concentrated on incorporating different sources of biological information to perform the MDA prediction task while failing to consider the fully potential utility of MDA network information at the motif-level. To overcome this problem, we propose a novel motif-aware MDA prediction model, namely MotifMDA, by fusing a variety of high- and low-order structural information. In particular, we first design several motifs of interest considering their ability to characterize how miRNAs are associated with diseases through different network structural patterns. Then, MotifMDA adopts a two-layer hierarchical attention to identify novel MDAs. Specifically, the first attention layer learns high-order motif preferences based on their occurrences in the given MDA network, while the second one learns the final embeddings of miRNAs and diseases through coupling high- and low-order preferences. Experimental results on two benchmark datasets have demonstrated the superior performance of MotifMDA over several state-of-the-art prediction models. This strongly indicates that accurate MDA prediction can be achieved by relying solely on MDA network information. Furthermore, our case studies indicate that the incorporation of motif-level structure information allows MotifMDA to discover novel MDAs from different perspectives.


Assuntos
Biologia Computacional , MicroRNAs , MicroRNAs/genética , Humanos , Biologia Computacional/métodos , Predisposição Genética para Doença/genética , Algoritmos
11.
J Transl Med ; 22(1): 316, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549133

RESUMO

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.


Assuntos
Propofol , Sepse , Camundongos , Humanos , Animais , Propofol/farmacologia , Propofol/uso terapêutico , Propofol/metabolismo , Receptor 4 Toll-Like/metabolismo , Modelos Animais de Doenças , Macrófagos/metabolismo , Sepse/complicações , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo
12.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38426324

RESUMO

Emerging clinical evidence suggests that sophisticated associations with circular ribonucleic acids (RNAs) (circRNAs) and microRNAs (miRNAs) are a critical regulatory factor of various pathological processes and play a critical role in most intricate human diseases. Nonetheless, the above correlations via wet experiments are error-prone and labor-intensive, and the underlying novel circRNA-miRNA association (CMA) has been validated by numerous existing computational methods that rely only on single correlation data. Considering the inadequacy of existing machine learning models, we propose a new model named BGF-CMAP, which combines the gradient boosting decision tree with natural language processing and graph embedding methods to infer associations between circRNAs and miRNAs. Specifically, BGF-CMAP extracts sequence attribute features and interaction behavior features by Word2vec and two homogeneous graph embedding algorithms, large-scale information network embedding and graph factorization, respectively. Multitudinous comprehensive experimental analysis revealed that BGF-CMAP successfully predicted the complex relationship between circRNAs and miRNAs with an accuracy of 82.90% and an area under receiver operating characteristic of 0.9075. Furthermore, 23 of the top 30 miRNA-associated circRNAs of the studies on data were confirmed in relevant experiences, showing that the BGF-CMAP model is superior to others. BGF-CMAP can serve as a helpful model to provide a scientific theoretical basis for the study of CMA prediction.


Assuntos
MicroRNAs , Humanos , MicroRNAs/genética , RNA Circular/genética , Curva ROC , Aprendizado de Máquina , Algoritmos , Biologia Computacional/métodos
13.
Ann Clin Lab Sci ; 54(1): 9-16, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38514066

RESUMO

OBJECTIVE: Gastrointestinal metaplasia (GIM) has a close relationship with gastric cancer (GC), but it is unclear how to judge which GIM could develop into GC. This study aimed to assess the role of CDX2 and its association with Helicobacter pylori (H.pylori) genotypes in GIM. METHODS: CagA and vacA genes were identified via PCR in 466 H. pylori-positive gastric tissues, including gastritis (n=104), GIM diagnosed endoscopically (GIM-1; n=82), gastric cancer (GC; n=173), and paired adjacent GIM tumors resected surgically (GIM-2; n=107). GIM was subclassified per the HID- AB pH2.5-PAS as follows: type I (n=23), type II (n=43), and type III (n=16) in GIM-1; type I (n=8), type II (n=40), and type III (n=59) in GIM-2. CDX2 expression was evaluated immunohistochemically. RESULTS: In GIM-1, the infection rate of vacAm2 (55.8%) and vacAs1m2 (53.5%) was higher in subtype II than in others (P<0.05), while that of vacAm1 (49.2%) and vacAs1m1 (33.9%) was higher in subtype III than in others. The cagA+ rate was higher in subtypes I (75.0%) and III (64.4%) than in subtype II (40.0%; P<0.05) respectively. CDX2 was upregulated in subtype I than in subtypes II and III in GIM-1 and GIM-2. In GIM-2 and GC, CDX2 was downregulated in vacAm1, vacAs1m1, and cagA+ (P<0.05). The predominant genotype was vacAs1m2 in subtype II of GIM-1, CDX2 expression remaining unaltered; however, the predominant genotype was cagA+ vacAs1m1 in subtypes II and III of GIM-2, negatively correlated with CDX2 expression. CONCLUSION: These GIM subtypes (cagA+ vacAs1m1 H. pylori-positive GIM with negative CDX2 expression) resemble GC and should be evaluated similar to cancerous GIM.


Assuntos
Fator de Transcrição CDX2 , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Fator de Transcrição CDX2/genética , Genótipo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Metaplasia/genética , Metaplasia/complicações , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
14.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38324624

RESUMO

Connections between circular RNAs (circRNAs) and microRNAs (miRNAs) assume a pivotal position in the onset, evolution, diagnosis and treatment of diseases and tumors. Selecting the most potential circRNA-related miRNAs and taking advantage of them as the biological markers or drug targets could be conducive to dealing with complex human diseases through preventive strategies, diagnostic procedures and therapeutic approaches. Compared to traditional biological experiments, leveraging computational models to integrate diverse biological data in order to infer potential associations proves to be a more efficient and cost-effective approach. This paper developed a model of Convolutional Autoencoder for CircRNA-MiRNA Associations (CA-CMA) prediction. Initially, this model merged the natural language characteristics of the circRNA and miRNA sequence with the features of circRNA-miRNA interactions. Subsequently, it utilized all circRNA-miRNA pairs to construct a molecular association network, which was then fine-tuned by labeled samples to optimize the network parameters. Finally, the prediction outcome is obtained by utilizing the deep neural networks classifier. This model innovatively combines the likelihood objective that preserves the neighborhood through optimization, to learn the continuous feature representation of words and preserve the spatial information of two-dimensional signals. During the process of 5-fold cross-validation, CA-CMA exhibited exceptional performance compared to numerous prior computational approaches, as evidenced by its mean area under the receiver operating characteristic curve of 0.9138 and a minimal SD of 0.0024. Furthermore, recent literature has confirmed the accuracy of 25 out of the top 30 circRNA-miRNA pairs identified with the highest CA-CMA scores during case studies. The results of these experiments highlight the robustness and versatility of our model.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , RNA Circular/genética , Funções Verossimilhança , Redes Neurais de Computação , Neoplasias/genética , Biologia Computacional/métodos
15.
Heliyon ; 10(4): e26121, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404843

RESUMO

Genome-wide sequencing allows for prediction of clinical treatment responses and outcomes by estimating genomic status. Here, we developed Genomic Status scan (GSscan), a long short-term memory (LSTM)-based deep-learning framework, which utilizes low-pass whole genome sequencing (WGS) data to capture genomic instability-related features. In this study, GSscan directly surveys homologous recombination deficiency (HRD) status independent of other existing biomarkers. In breast cancer, GSscan achieved an AUC of 0.980 in simulated low-pass WGS data, and obtained a higher HRD risk score in clinical BRCA-deficient breast cancer samples (p = 1.3 × 10-4, compared with BRCA-intact samples). In ovarian cancer, GSscan obtained higher HRD risk scores in BRCA-deficient samples in both simulated data and clinical samples (p = 2.3 × 10-5 and p = 0.039, respectively, compared with BRCA-intact samples). Moreover, HRD-positive patients predicted by GSscan showed longer progression-free intervals in TCGA datasets (p = 0.0011) treated with platinum-based adjuvant chemotherapy, outperforming existing low-pass WGS-based methods. Furthermore, GSscan can accurately predict HRD status using only 1 ng of input DNA and a minimum sequencing coverage of 0.02 × , providing a reliable, accessible, and cost-effective approach. In summary, GSscan effectively and accurately detected HRD status, and provide a broadly applicable framework for disease diagnosis and selecting appropriate disease treatment.

16.
Neoplasia ; 48: 100960, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38184887

RESUMO

BACKGROUND: Cisplatin resistance is one of the major obstacles in non-small cell lung cancer (NSCLC) treatment. Intriguingly, elevated lactate levels were observed in cisplatin-resistant cells, which spurred further investigation into their underlying biological mechanisms. METHODS: Lactate levels were measured by lactate detection kit. Cisplatin-resistance NSCLC cells were established using progressive concentration of cisplatin. Cell viability, proliferation, and apoptosis were detected by CCK-8, EdU, and flow cytometry, respectively. Cell proliferation in vivo was determined by immunohistochemistry of Ki67 and apoptotic cells were calculated by the TUNEL. MeRIP-PCR was used to measure FOXO3 m6A levels. The interactions of genes were analyzed via RIP, ChIP, Dual-luciferase reporter, and RNA pull-down, respectively. RESULTS: Elevated lactate levels were observed in both NSCLC patients and cisplatin-resistance cells. Lactate treatment increased cisplatin-resistance cell viability in vitro and promoted tumor growth in vivo. Mechanistically, lactate downregulated FOXO3 by YTHDF2-mediated m6A modification. FOXO3 transcriptionally reduced MAGI1-IT1 expression. FOXO3 overexpression inhibited the lactate-induced promotion of cisplatin resistance in NSCLC, which were reversed by MAGI1-IT1 overexpression. MAGI1-IT1 and IL6R competitively bound miR-664b-3p. FOXO3 overexpression or MAGI1-IT1 knockdown repressed lactate-mediated cisplatin resistance in vivo. CONCLUSION: Lactate promoted NSCLC cisplatin resistance through regulating FOXO3/MAGI1-IT1/miR-664b-3p/IL6R axis in YTHDF2-mediated m6A modification.


Assuntos
Adenina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas , Proteína Forkhead Box O3 , Neoplasias Pulmonares , MicroRNAs , Humanos , Ácido Láctico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Cisplatino/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Fatores de Transcrição , Proliferação de Células , MicroRNAs/genética , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Moléculas de Adesão Celular , Proteínas Adaptadoras de Transdução de Sinal , Guanilato Quinases
17.
Nanotechnology ; 35(20)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38286015

RESUMO

A transfer-free graphene with high magnetoresistance (MR) and air stability has been synthesized using nickel-catalyzed atmospheric pressure chemical vapor deposition. The Raman spectrum and Raman mapping reveal the monolayer structure of the transfer-free graphene, which has low defect density, high uniformity, and high coverage (>90%). The temperature-dependent (from 5 to 300 K) current-voltage (I-V) and resistance measurements are performed, showing the semiconductor properties of the transfer-free graphene. Moreover, the MR of the transfer-free graphene has been measured over a wide temperature range (5-300 K) under a magnetic field of 0 to 1 T. As a result of the Lorentz force dominating above 30 K, the transfer-free graphene exhibits positive MR values, reaching ∼8.7% at 300 K under a magnetic field (1 Tesla). On the other hand, MR values are negative below 30 K due to the predominance of the weak localization effect. Furthermore, the temperature-dependent MR values of transfer-free graphene are almost identical with and without a vacuum annealing process, indicating that there are low density of defects and impurities after graphene fabrication processes so as to apply in air-stable sensor applications. This study opens avenues to develop 2D nanomaterial-based sensors for commercial applications in future devices.

18.
Metab Brain Dis ; 39(1): 147-171, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37542622

RESUMO

Schizophrenia is a devastating neuropsychiatric disorder affecting 1% of the world population and ranks as one of the disorders providing the most severe burden for society. Schizophrenia etiology remains obscure involving multi-risk factors, such as genetic, environmental, nutritional, and developmental factors. Complex interactions of genetic and environmental factors have been implicated in the etiology of schizophrenia. This review provides an overview of the historical origins, pathophysiological mechanisms, diagnosis, clinical symptoms and corresponding treatment of schizophrenia. In addition, as schizophrenia is a polygenic, genetic disorder caused by the combined action of multiple micro-effective genes, we further detail several approaches, such as candidate gene association study (CGAS) and genome-wide association study (GWAS), which are commonly used in schizophrenia genomics studies. A number of GWASs about schizophrenia have been performed with the hope to identify novel, consistent and influential risk genetic factors. Finally, some schizophrenia susceptibility genes have been identified and reported in recent years and their biological functions are also listed. This review may serve as a summary of past research on schizophrenia genomics and susceptibility genes (NRG1, DISC1, RELN, BDNF, MSI2), which may point the way to future schizophrenia genetics research. In addition, depending on the above discovery of susceptibility genes and their exact function, the development and application of antipsychotic drugs will be promoted in the future.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/diagnóstico , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Genômica , Proteínas de Ligação a RNA/genética
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