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1.
Clin Exp Med ; 24(1): 65, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564026

RESUMO

Observational studies showed possible associations between systemic lupus erythematosus and multiple myeloma. However, whether there is a casual relationship between different types of autoimmune diseases (type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, multiple sclerosis, primary sclerosing cholangitis, primary biliary cirrhosis, and juvenile idiopathic arthritis) and multiple myeloma (MM) is not well known. We performed a two-sample Mendelian randomization (MR) study to estimate the casual relationship. Summary-level data of autoimmune diseases were gained from published genome-wide association studies while data of MM was obtained from UKBiobank. The Inverse-Variance Weighted (IVW) method was used as the primary analysis method to interpret the study results, with MR-Egger and weighted median as complementary methods of analysis. There is causal relationship between primary sclerosing cholangitis [OR = 1.00015, 95% CI 1.000048-1.000254, P = 0.004] and MM. Nevertheless, no similar causal relationship was found between the remaining seven autoimmune diseases and MM. Considering the important role of age at recruitment and body mass index (BMI) in MM, we excluded these relevant instrument variables, and similar results were obtained. The accuracy and robustness of these findings were confirmed by sensitivity tests. Overall, MR analysis suggests that genetic liability to primary sclerosing cholangitis could be causally related to the increasing risk of MM. This finding may serve as a guide for clinical attention to patients with autoimmune diseases and their early screening for MM.


Assuntos
Doenças Autoimunes , Colangite Esclerosante , Lúpus Eritematoso Sistêmico , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doenças Autoimunes/genética
2.
Heliyon ; 10(6): e27822, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515679

RESUMO

People are an organic unity. Every organ of our body doesn't exist alone. They are a part of our body and have important connections with other tissues or organs. The gut-lung axis is a typical example. Here, we reviewed the current research progress of the gut-lung axis. The main cross-talk between the intestine and lungs was sorted out, i.e. the specific interaction content contained in the gut-lung axis. We determine a relatively clear concept for the gut-lung axis, that is, the gut-lung axis is a cross-talk that the gut and lungs interact with each other through microorganisms and the immune system to achieve bidirectional regulation. The gut and lungs communicate with each other mainly through the immune system and symbiotic microbes, and these two pathways influence each other. The portal vein system and mesenteric lymphatics are the primary communication channels between the intestine and lungs. We also summarized the effects of pneumonia, including Coronavirus disease 2019 (COVID-19) and Community-Acquired Pneumonia (CAP), on intestinal microbes and immune function through the gut-lung axis, and discussed the mechanism of this effect. Finally, we explored the value of intestinal microbes and the gut-lung axis in the treatment of pneumonia through the effect of intestinal microbes on pneumonia.

3.
J Phys Chem Lett ; 15(10): 2765-2771, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482678

RESUMO

Gilvocarcin V (GV) is a natural antibiotic exhibiting excellent antitumor activities and remarkably low toxicity in near-ultraviolet or visible light-dependent treatment. Notwithstanding, the [2 + 2] cycloaddition reaction between GV and thymine has been proven to be the key for its function in photodynamic therapy, and crucial mechanistic details about such a reaction are poorly understood. In this study, the electronic relaxation pathways and photoaddition reaction are characterized by femto- to nanosecond time-resolved spectroscopy combined with quantum chemical calculation. Our results reveal that ultrafast intersystem crossing (<3 ps) leads to the population of a local triplet excited state in DNA-intercalated GV. Such a state can further induce the formation of a biradical state, which is identified as the important reactive precursor for photoaddition between GV and thymine. The overall photoaddition quantum efficiency is determined to be 11.57 ± 1.0%. These results are essential to the elucidation of the DNA photoaddition mechanism of C-aryl glycoside-based artificial photocytotoxic agents and could help further development of those medicines.


Assuntos
Cumarínicos , Glicosídeos , Timina , Timina/química , DNA/química , Antibacterianos
4.
Clin Appl Thromb Hemost ; 30: 10760296241238015, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529627

RESUMO

To investigate the effect of reduced early-pregnancy activated partial thrombin time (APTT), prothrombin time (PT), and international standardized ratio (INR) on the risk of preeclampsia. A total of 8549 pregnant women with singleton births were included. Early pregnancy APTT, PT, and INR levels, with age, birth, prepregnancy body mass index, fibrinogen (FBG), thrombin time (TT), D-dimer (DD2), antithrombin III (ATIII), fibrin degradation products (FDP) as confounders, generalized linear model of APTT, the relative risk of PT and INR when INR reduction. After adequate adjustment for confounders, the relative risk of preeclampsia was 0.703 for every 1 s increase in plasma PT results in early pregnancy, and for every 0.1 increase in plasma INR results, the relative risk of preeclampsia was 0.767. With a PT less than the P25 quantile (<11 s), the relative risk of preeclampsia was 1.328. The relative risk of preeclampsia at an INR less than the P25 quantile (<0.92) was 1.24. There was no statistical association between APTT on the risk of preeclampsia. The relative risk of preeclampsia is strongly associated with a decrease in PT and INR in early pregnancy. PT and INR in early pregnancy were a potential marker in the risk stratification of preeclampsia. Focusing on reduced PT and INR levels in early pregnancy can help to identify early pregnancies at risk for preeclampsia.


Assuntos
Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Coeficiente Internacional Normatizado , Pré-Eclâmpsia/epidemiologia , Estudos Retrospectivos , Testes de Coagulação Sanguínea , Tempo de Protrombina , Tempo de Tromboplastina Parcial
6.
MethodsX ; 12: 102572, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38352663

RESUMO

Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor (TGF-ß) superfamily, and is expressed and secreted in response to inflammation, oxidative stress and hypoxia. It has been shown in several studies to be a predictor of heart failure. However, the only kits available on the market are ELISA kits, which are costly and error-prone and are not conducive for clinical use. Here, we developed a chemiluminescence kit which optimized the reaction conditions and the reaction time was reduced to 10 min. We further proved that it can be used to measure GDF-15 in serum or plasma accurately and fastly, and provide additional information for the diagnosis of heart failure disease. Methodological comparison and clinical study verified this method is a reliable, economical and highly automated blood test method.•All necessary steps and the reagents needed are provided.•Reliability of the chemiluminescence immunoassay was verified by analyzing serum GDF-15 levels from different groups.•GDF-15 can provide clinicians with reliable prediction and disease assessment of heart failure.

7.
Heliyon ; 10(3): e25409, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38327465

RESUMO

Background/Objective: Reticulocyte hemoglobin content (MCHr) was recognized as a rapid and reliable marker for investigating iron deficiency (ID). We hypothesized that MCHr was associated with the risk of iron deficiency anemia in adults. Methods: This is a dual-center case-control study. A total of 806 patients and healthy individuals were recruited from Ruijin Hospital and Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine between January 2021 and December 2021. The participants were categorized into iron deficiency anemia (IDA) group (n = 302), non-IDA group (n = 366), and healthy control group (n = 138). According to the MCHr level, the participants were divided into two groups, i.e. normal MCHr (≥25 pg) and decreased MCHr (<25 pg) group. Multivariate logistic regression analysis and adjusted subgroup analysis were conducted to estimate the relative risk between MCHr and IDA, with confounding factors including age, sex, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), Hematocrit (HCT), serum iron (Fe), ferritin (Ferrit), and total iron binding capacity (TIBC). Results: Compared with the non-IDA, the MCHr level with IDA decreased significantly. ROC curve analysis showed that MCHr had the largest area under the AUC curve. After comprehensive adjustment for confounding factors, individuals with normal level of MCHr exhibited a decreased risk of IDA (OR = 0.68 [0.60, 0.77], P < 0.01), while the risk of IDA was up to 5 times higher for those with decreased MCHr. Conclusion: Our findings supported the hypothesis that MCHr was associated with the risk of IDA in adults and could serve as an indicator of IDA severity. MCHr holds clinical value as an auxiliary diagnostic indicator, providing valuable insights into whether invasive examinations are warranted in the assessment of IDA.

8.
Ren Fail ; 46(1): 2303395, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38264967

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication in severe acute pancreatitis (AP), associated with high mortality rate. Early detection of AKI is crucial for prompt intervention and better outcomes. This study aims to develop and validate predictive models using machine learning (ML) to identify the onset of AKI in patients with AP. METHODS: Patients with AP were extracted from the MIMIC-IV database. We performed feature selection using the random forest method. Model construction involved an ensemble of ML, including random forest (RF), support vector machine (SVM), k-nearest neighbors (KNN), naive Bayes (NB), neural network (NNET), generalized linear model (GLM), and gradient boosting machine (GBM). The best-performing model was fine-tuned and evaluated through split-set validation. RESULTS: We analyzed 1,235 critically ill patients with AP, of which 667 cases (54%) experienced AKI during hospitalization. We used 49 variables to construct models, including GBM, GLM, KNN, NB, NNET, RF, and SVM. The AUC for these models was 0.814 (95% CI, 0.763 to 0.865), 0.812 (95% CI, 0.769 to 0.854), 0.671 (95% CI, 0.622 to 0.719), 0.812 (95% CI, 0.780 to 0.864), 0.688 (95% CI, 0.624 to 0.752), 0.809 (95% CI, 0.766 to 0.851), and 0.810 (95% CI, 0.763 to 0.856) respectively. In the test set, the GBM's performance was consistent, with an area of 0.867 (95% CI, 0.831 to 0.903). CONCLUSIONS: The GBM model's precision is crucial, aiding clinicians in identifying high-risk patients and enabling timely interventions to reduce mortality rates in critical care.


Assuntos
Injúria Renal Aguda , Pancreatite , Humanos , Doença Aguda , Teorema de Bayes , Estado Terminal , Aprendizado de Máquina
9.
Cogn Res Princ Implic ; 8(1): 73, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38117413

RESUMO

While the role of emotion in leadership practice is well-acknowledged, there is still a lack of clarity regarding the behavioral distinctions between individuals with varying levels of leadership and the underlying neurocognitive mechanisms at play. This study utilizes facial emotion recognition in conjunction with electroencephalograms to explore the temporal dynamics of facial emotion recognition processes among college students with high and low levels of leadership. The results showed no significant differences in the amplitude of P1 during the early stage of facial emotion recognition between the two groups. In the middle stage of facial emotion recognition, the main effect of group was significant on the N170 component, with higher N170 amplitude evoked in high-leadership students than low-leadership students. In the late stage of facial emotion recognition, low-leadership students evoked greater LPP amplitude in the temporal-parietal lobe when recognizing happy facial emotions compared to high-leadership students. In addition, time-frequency results revealed a difference in the alpha frequency band, with high-leadership students exhibiting lower alpha power than low-leadership students. The results suggest differences in the brain temporal courses of facial emotion recognition between students with different leadership levels, which are mainly manifested in the middle stage of structural encoding and the late stage of delicate emotional processing during facial emotion recognition.


Assuntos
Reconhecimento Facial , Humanos , Liderança , Potenciais Evocados , Eletroencefalografia , Estudantes
10.
Int J Gen Med ; 16: 5355-5362, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38021071

RESUMO

Purpose: To explore the relationship between the systemic inflammation response index (SIRI) and postoperative delirium (POD) in older patients with hip arthroplasty surgery. Patients and Methods: Older patients who underwent elective hip arthroplasty surgery were included in this retrospective study. SIRI, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were collected from blood routine examination at admission. Binary logistic regression analysis was performed to evaluate the association between SIRI levels and POD was analyzed. Results: Ultimately, 116 older patients who met the inclusion criteria were assessed. Thirty-four (29%) of 116 patients diagnosed with POD were defined as the POD group, and the rest consisted of the Non-POD group. Compared with non-POD patients, POD patients showed significantly higher levels of SIRI (P < 0.001) and NLR (P = 0.002) at admission. There was no significance in the levels of PLR between two groups. SIRI was independently associated with the occurrence of POD in multivariate logistic regression analysis [odds ratio (OR) = 3.34, 95% confidence interval (95% CI) = 1.26-8.85, P = 0.016]. Receiver operating characteristic curve analysis indicated that SIRI with an optimal cutoff value of 0.987 predicted the POD with a sensitivity of 88.2% and specificity of 74.4%, and the area under the curve was 0.82 (95% CI, 0.74-0.90, P < 0.01). Conclusion: Preoperative SIRI and NLR levels in the blood are associated with the occurrence of POD. Moreover, preoperative SIRI level is a useful candidate biomarker to identify delirium after elective hip arthroplasty surgery in older patients.

11.
Med Mycol ; 61(10)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37777835

RESUMO

Candida tropicalis, a human conditionally pathogenic yeast, is distributed globally, especially in Asia-Pacific. The increasing morbidity and azole resistance of C. tropicalis have made clinical treatment difficult. The correlation between clonality and antifungal susceptibility of clinical C. tropicalis isolates has been reported. To study the putative correlation in C. tropicalis isolated from normally sterile body fluid specimens and explore the distinct clonal complex (CC) in Hefei, 256 clinical C. tropicalis isolates were collected from four teaching hospitals during 2016-2019, of which 30 were fluconazole-resistant (FR). Genetic profiles of 63 isolates, including 30 FR isolates and 33 fluconazole-susceptible (FS) isolates, were characterized using multilocus sequence typing (MLST). Phylogenetic analysis of the data was conducted using UPGMA (unweighted pair group method with arithmetic averages) and the minimum spanning tree algorithm. MLST clonal complexes (CCs) were analyzed using the goeBURST package. Among 35 differentiated diploid sequence types (DSTs), 16 DSTs and 1 genotype were identified as novel. A total of 35 DSTs were assigned to five major CCs based on goeBURST analysis. CC1 (containing DST376, 505, 507, 1221, 1222, 1223, 1226, and 1229) accounted for 86.7% (26/30) of the FR isolates. However, the genetic relationships among the FS isolates were relatively decentralized. The local FR CC1 belongs to a large fluconazole non-susceptible CC8 in global isolates, of which the putative founder genotype was DST225. The putative correlation between MLST types and antifungal susceptibility of clinical C. tropicalis isolates in Hefei showed that DSTs are closely related to FR clones.


A local prevalent FR CC1, accounted for 86.7% of the FR isolates in Hefei, China, which showed that fluconazole resistance is closely related to the genetic background, a finding of great value to local medical treatment and possible reasons for the increase in azole resistance of Candida tropicalis.


Assuntos
Líquidos Corporais , Fluconazol , Humanos , Fluconazol/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida tropicalis/genética , Tipagem de Sequências Multilocus/veterinária , Filogenia , Farmacorresistência Fúngica , China , Células Clonais , Testes de Sensibilidade Microbiana/veterinária
12.
Sci Rep ; 13(1): 18372, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884566

RESUMO

The non-receptor protein tyrosine phosphatases gene family (PTPNs) is involved in the tumorigenesis and development of many cancers, but the role of PTPNs in acute myeloid leukemia (AML) remains unclear. After a comprehensive evaluation on the expression patterns and immunological effects of PTPNs using a pan-cancer analysis based on RNA sequencing data obtained from The Cancer Genome Atlas, the most valuable gene PTPN2 was discovered. Further investigation of the expression patterns of PTPN2 in different tissues and cells showed a robust correlation with AML. PTPN2 was then systematically correlated with immunological signatures in the AML tumor microenvironment and its differential expression was verified using clinical samples. In addition, a prediction model, being validated and compared with other models, was developed in our research. The systematic analysis of PTPN family reveals that the effect of PTPNs on cancer may be correlated to mediating cell cycle-related pathways. It was then found that PTPN2 was highly expressed in hematologic diseases and bone marrow tissues, and its differential expression in AML patients and normal humans was verified by clinical samples. Based on its correlation with immune infiltrates, immunomodulators, and immune checkpoint, PTPN2 was found to be a reliable biomarker in the immunotherapy cohort and a prognostic predictor of AML. And PTPN2'riskscore can accurately predict the prognosis and response of cancer immunotherapy. These findings revealed the correlation between PTPNs and immunophenotype, which may be related to cell cycle. PTPN2 was differentially expressed between clinical AML patients and normal people. It is a diagnostic biomarker and potentially therapeutic target, providing targeted guidance for clinical treatment.


Assuntos
Leucemia Mieloide Aguda , Proteína Tirosina Fosfatase não Receptora Tipo 2 , Humanos , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Carcinogênese , Biomarcadores , Medição de Risco , Prognóstico , Microambiente Tumoral/genética
13.
Nat Commun ; 14(1): 5077, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37604832

RESUMO

Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.


Assuntos
COVID-19 , Trombose , Humanos , Animais , Camundongos , SARS-CoV-2 , Ativação Plaquetária , Coagulação Sanguínea , Fatores de Transcrição , Antígenos CD36/genética
14.
Autophagy ; 19(12): 3062-3078, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37533292

RESUMO

ABBREVIATIONS: 3-MA, 3-methyladenine; AIE, aggregation-induced emission; AIEgens, aggregation-induced emission luminogens; ATG5, autophagy related 5; BMDM, bone marrow-derived macrophage; CQ, chloroquine; DiD, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate; DiO, 3,3'-dioctadecyloxacarbocyanine perchlorate; DMSO, dimethyl sulfoxide; d-THP-1, differentiated THP-1; FACS, fluorescence activated cell sorting; FBS, fetal bovine serum; FCCP, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone; GABARAP, GABA type A receptor-associated protein; GFP, green fluorescent protein; HBSS, Hanks' balanced salt solution; HPLC, high-performance liquid chromatography; HRP, horseradish peroxidase; IL1B, interleukin 1 beta; KT, an AIE probe composed of a cell-penetrating peptide and an AIEgen tetraphenyl ethylene; LC3-II, lipidated LC3; LDH, lactate dehydrogenase; LIR, LC3-interacting region; LKR, engineered molecular probe composed of an LC3-interacting peptide, a cell-penetrating peptide and a non-AIE fluorescent molecule rhodamine; LKT, engineered molecular probe composed of an LC3-interacting peptide, a cell-penetrating peptide and an AIEgen tetraphenyl ethylene; LPS, lipopolysaccharide; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MEF, mouse embryonic fibroblast; mRFP, monomeric red fluorescent protein; NHS, N-hydroxysuccinimide; NLRP3, NLR family pyrin domain containing 3; PBS, phosphate-buffered saline; PCC, pearson's correlation coefficient; PL, photoluminescence; PMA, phorbol 12-myristate 13-acetate; RAP, rapamycin; RIM, restriction of intramolecular motions; s.e.m., standard error of the mean; SPR, surface plasmon resonance; SQSTM1/p62, sequestosome 1; TAX1BP1, Tax1 binding protein 1; TPE, tetraphenylethylene; TPE-yne, 1-(4-ethynylphenyl)-1,2,2-triphenylethene; Tre, trehalose; u-THP-1: undifferentiated THP-1; UV-Vis, ultraviolet visible.


Assuntos
Autofagia , Peptídeos Penetradores de Células , Animais , Camundongos , Fibroblastos/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Fluorescência Verde , Sondas Moleculares , Etilenos
16.
J Phys Chem B ; 127(31): 6878-6886, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37490365

RESUMO

Methylation at the C5 position of cytosine, a naturally occurring epigenetic modification on DNA, shows a high correlation with mutational hotspots in disease such as skin cancer. Due to its essential biological relevance, numerous studies were devoted to confirming that the methylated sites favor the formation of the cyclobutane pyrimidine dimer (CPD), a well-known UV-induced lesion. However, photophysical and photochemical properties of dinucleotides and polynucleotides containing 5-methylcytosine (5mC) remain elusive. Herein, a charge transfer (CT) triplet state, generated via intersystem crossing (ISC) from a CT singlet state that enhanced after methylation on cytosine, is directly observed by using femtosecond transient absorption (TA) and time-resolved mid-infrared (TRIR) spectroscopy together with quantum chemical calculations for the first time in the T5mC dimer. Such an ISC process is quenched due to limitations of the ground-state geometries in 5mC-containing single-strand oligomer d(T5mC)9. This mechanistic information is important for understanding the early stage of triplet state-induced CPD formation in 5mC containing DNA.


Assuntos
5-Metilcitosina , Dímeros de Pirimidina , Dímeros de Pirimidina/química , Dano ao DNA , Citosina/química , DNA/química
17.
Heliyon ; 9(7): e17983, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37496928

RESUMO

Normal pregnancy is a hypercoagulable state with an increase in coagulation factor levels and a decrease in natural anticoagulation. However, a higher hypercoagulable state with prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), increased D-dimer, and mean platelet volume is seen in women with preeclampsia at the time of onset. In addition, endothelial dysfunction occurs before the clinical symptoms of preeclampsia. Therefore, we undertook this study to investigate the coagulation profile in the first trimester in women who developed preeclampsia later. A total of 853 pregnant women with singleton births at the Obstetrics and Gynecology Hospital of Fudan University between January 2021 and December 2021 were included in this case-control study. In the comparison with the controls (n = 531), the mean value of D-dimer, APTT, thrombin time (TT), antithrombin (AT)), and fibrin degradation products (FDP) was significantly lower in preeclamptic women at the time of diagnosis (n = 322). The changes in the coagulation profile were not associated with the severity or the time of onset. The reduced values of D-dimer, AT, and FDP, and increased values of TT were also observed in the first trimester in women who developed preeclampsia later and were not associated with the severity, or the time of onset of preeclampsia. After adjusting for maternal age and BMI, the values of D-dimer and AT in the first trimester were correlated to the risk of developing preeclampsia. Our findings suggest that there is an abnormal maternal response to the hemostatic system in early gestational age in women who developed preeclampsia later and measuring the coagulation profile could be an additional predictive marker of preeclampsia.

18.
Phys Chem Chem Phys ; 25(22): 15153-15161, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37221896

RESUMO

N 6-Hydroxymethyladenosine (hm6A) and N6-formyladenosine (f6A) are two important intermediates during the demethylation process of N6-methyladenosine (m6A), which has been proven to show epigenetic function in mRNA. However, there is no knowledge about how the chemical integrity and stability could be altered when these two nucleosides are exposed to ultraviolet (UV) radiation. Herein, we report the first study on excited state dynamics of hm6A and f6A in solutions by using femtosecond time-resolved spectroscopy and quantum chemistry calculations. Surprisingly, triplet excited species are clearly identified in both hm6A and f6A after UV excitation, which is in sharp contrast to the 10-3 level triplet yield of adenosine scaffolds. Moreover, the doorway states leading to triplet states are found to be an intramolecular charge transfer state and a lower-lying dark nπ* state in hm6A and f6A, respectively. These discoveries pave the way to further study their effects on RNA strands and provide insight for understanding RNA photochemistry.


Assuntos
Nucleosídeos , RNA , RNA/química , RNA Mensageiro , Análise Espectral , Epigênese Genética
19.
Chaos ; 33(2): 023120, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36859197

RESUMO

Neuromorphic computing provides unique computing and memory capabilities that could break the limitation of conventional von Neumann computing. Toward realizing neuromorphic computing, fabrication and synthetization of hardware elements and circuits to emulate biological neurons are crucial. Despite the striking progress in exploring neuron circuits, the existing circuits can only reproduce monophasic action potentials, and no studies report on circuits that could emulate biphasic action potentials, limiting the development of neuromorphic devices. Here, we present a simple third-order memristive circuit built with a classical symmetrical Chua Corsage Memristor (SCCM) to accurately emulate biological neurons and show that the circuit can reproduce monophasic action potentials, biphasic action potentials, and chaos. Applying the edge of chaos criterion, we calculate that the SCCM and the proposed circuit have the symmetrical edge of chaos domains with respect to the origin, which plays an important role in generating biphasic action potentials. Also, we draw a parameter classification map of the proposed circuit, showing the edge of chaos domain (EOCD), the locally active domain, and the locally passive domain. Near the calculated EOCD, the third-order circuit generates monophasic action potentials, biphasic action potentials, chaos, and ten types of symmetrical bi-directional neuromorphic phenomena by only tuning the input voltage, showing a resemblance to biological neurons. Finally, a physical SCCM circuit and some experimentally measured neuromorphic waveforms are exhibited. The experimental results agree with the numerical simulations, verifying that the proposed circuit is suitable as artificial neurons.

20.
Blood Transfus ; 21(2): 146-156, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35175191

RESUMO

BACKGROUND: Platelets are anucleated blood cells and contain various RNA species. We investigated the changes in the whole transcriptome expression profile of platelet concentrates (PC) during storage to explore biological functions and biomarkers in platelet storage damage. MATERIALS AND METHODS: Platelets were collected by apheresis from eight healthy blood donors and stored from day 0 to day 4. Platelet phenotyping and function analysis were used to detect platelet activity during storage. RNA-sequencing was used to detect changes in expression of mRNA, lncRNA and circRNA in the PC during storage. Gene ontology and KEGG analyses were applied to predict the functional distribution of differential expression of mRNA. Gene set enrichment analysis was used to analyze the differential levels of gene pathways. Finally, polymerase chain reaction (PCR) analysis was performed to verify the expression of three mRNA (POLE2, DCUN1D4, DAD1). RESULTS: In total, 10,767 mRNA, 2,923 lncRNA and 68,550 circRNA were detected in the PC by RNA-sequencing. The expression levels of 222 mRNA changed significantly from day 0 to day 4 of storage: 58 increased continuously and 145 decreased continuously. Differentially expressed mRNA may be involved in physiological processes such as platelet activation, platelet aggregation, endocytosis, and apoptosis. Expression levels of 1,413 lncRNA were obvious. The levels of 42 species increased and the levels of 28 species decreased. The expression levels of 198 species of circRNA changed significantly, with those of 13 species changing continuously. The differential levels of expression of DAD1, DCUN1D4 and POLE1 mRNA, shown by RNA sequencing, were validated by PCR assay. DISCUSSION: Changes in mRNA, lncRNA and circRNA during platelet storage may be closely related to platelet apoptosis and physiological functions in the platelet storage lesion. The expression levels of DAD1, DCUN1D4 and POLE1 could be biomarkers to monitor platelet status in PC bags.


Assuntos
RNA Circular , RNA Longo não Codificante , Humanos , RNA Circular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Preservação de Sangue , Plaquetas/metabolismo , Biomarcadores/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Perfilação da Expressão Gênica
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