RESUMO

Endoplasmic reticulum stress-induced cell apoptosis is a pivotal mechanism underlying the progression of cardiac hypertrophy. NLRX1, a member of the NOD-like receptor family, modulates various cellular processes, including STING, NF-κB, MAPK pathways, reactive oxygen species production, essential metabolic pathways, autophagy and cell death. Emerging evidence suggests that NLRX1 may offer protection against diverse cardiac diseases. However, the impacts and mechanisms of NLRX1 on endoplasmic reticulum stress in cardiac hypertrophy remains largely unexplored. In our study, we observed that the NLRX1 and phosphorylated STING (p-STING) were highly expressed in both hypertrophic mouse heart and cellular model of cardiac hypertrophy. Whereas over-expression of NLRX1 mitigated the expression levels of p-STING, as well as the endoplasmic reticulum stress markers, including transcription activating factor 4 (ATF4), C/EBP homologous protein (CHOP) and the ratios of phosphorylated PERK to PERK, phosphorylated IRE1 to IRE1 and phosphorylated eIF2α to eIF2α in an Angiotensin II (Ang II)-induced cellular model of cardiac hypertrophy. Importantly, the protective effects of NLRX1 were attenuated upon pretreatment with the STING agonist, DMXAA. Our findings provide the evidence that NLRX1 attenuates the PERK-eIF2α-ATF4-CHOP axis of endoplasmic reticulum stress response via inhibition of p-STING in Ang II-treated cardiomyocytes, thereby ameliorating the development of cardiac hypertrophy.

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Tuberculosis is a highly infectious disease caused by the bacterium Mycobacterium tuberculosis, and the spread of this agent has caused serious health problems worldwide. The rapid and accurate detection of M. tuberculosis is essential for controlling the spread of infection and for preventing the emergence of multidrug-resistant strains. In this study, the powerful trans-cleavage ability of CRISPR-Cas12a for ssDNA was combined with a surface-enhanced Raman spectroscopy (SERS)-based strategy to establish a CRISPR-SERS sensor for the hypersensitive detection of M. tuberculosis DNA. We observed a linear relationship between the concentration of M. tuberculosis DNA and the output signal over the range of 5 to 100 pM. The equation describing the standard curve was y = 24.10x + 1594, with R2 = 0.9914. The limit of detection was as low as 4.42 pM for genomic DNA, and a plasmid containing an M. tuberculosis-specific sequence was detected at 5 copy/µL. A detection accuracy of 100% was achieved in the analysis of DNA isolated from the sputum of hospitalized patients with tuberculosis. The entire detection process is simple to deploy and only takes 50 min and results in the sensitive and specific detection of M. tuberculosis DNA. This study provides a new method for the detection of tuberculosis. The tool is stable and can be utilized on-site, and it thus broadens the diagnostic application of CRISPR-Cas12a-based sensor technology.

RESUMO

BACKGROUND: Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. RESULTS: Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. CONCLUSIONS: This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules.

Assuntos

Nanopartículas , Óxido Nítrico , Fotoquimioterapia , Fármacos Fotossensibilizantes , Dióxido de Silício , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Nanopartículas/química , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Humanos , Dióxido de Silício/química , Animais , Camundongos , Linhagem Celular Tumoral , Raios Infravermelhos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Cutâneas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Camundongos Endogâmicos BALB C

RESUMO

BACKGROUND: Plants that contain brewing microorganisms are used in traditional fermentation starters, which are an essential part of local diet, nutrition, life, and health. Regionally, the plant species used and the microorganisms included in traditional fermentation starters are diverse, endowing local fermented drinks with different flavors and health benefits. However, related traditional knowledge has been scarcely documented or revealed. METHODS: An ethnobotanical survey was conducted in five towns of Nayong County in northwestern Guizhou, China. Snowball sampling, semi-structured interviews, free lists, and participatory observation were used to collect information on Jiuqu Plants (JPs) and jiuqu-making techniques. The PacBio platform was used to study the microbial community structure and diversity in the Chuanqing people's jiuqu. RESULTS: In total, 225 informants were interviewed, including 116 who provided plants and technological processes for making Chinese baijiu jiuqu (CBJ) and 139 who provided information about making fermented glutinous rice jiuqu (FGRJ). This study found that older people have more abundant knowledge about CBJ plants. Poaceae was found to be the dominant family used in making CBJ and FGRJ (7 species each). Compared to individual plant parts, the whole plant is most commonly used in two kinds of jiuqu (19.5% in CBJ and 22.6% in FGRJ). The Chuanqing people's jiuqu is used to treat dietary stagnation and indigestion. The highest relative frequency of citation of the CBJ plant was Ficus tikoua Bureau, and the counterpart of the FGRJ plant was Buddleja macrostachya Benth. The dominant bacterial species in jiuqu were Gluconobacter japonicus (YQ1, YQ4) and Pediococcus pentosaceus (YQ2, YQ3), and the dominant fungal species was Rhizopus oryzae. CONCLUSION: For the first time, this study documents the unique traditional jiuqu knowledge and reveals the microbial mystery behind the FGRJ of the Chuanqing people. Therefore, this study encourages the use of online social media platforms in order to spread Jiuqu culture, the use of the new media wave in order to create multimedia databases, and also suggests that local communities should develop preservation intervention programs, in addition to nurturing the inheritors in order to prevent the disappearance of traditional Jiuqu knowledge. This research contributes to the conservation and demystification of the traditional jiuqu knowledge of the Chuanqing people and lays the foundation for further research on its microbiology, nutrition, and metabolomics.

Assuntos

Etnobotânica , Fermentação , China , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Alimentos Fermentados/microbiologia , Adulto Jovem

RESUMO

Because of its rapid progression and frequently poor prognosis, stroke is the third major cause of death in Europe and the first one in China. Many independent studies demonstrated sufficient space for prevention interventions in the primary care of ischemic stroke defined as the most cost-effective protection of vulnerable subpopulations against health-to-disease transition. Although several studies identified molecular patterns specific for IS in body fluids, none of these approaches has yet been incorporated into IS treatment guidelines. The advantages and disadvantages of individual body fluids are thoroughly analyzed throughout the paper. For example, multiomics based on a minimally invasive approach utilizing blood and its components is recommended for real-time monitoring, due to the particularly high level of dynamics of the blood as a body system. On the other hand, tear fluid as a more stable system is recommended for a non-invasive and patient-friendly holistic approach appropriate for health risk assessment and innovative screening programs in cost-effective IS management. This article details aspects essential to promote the practical implementation of highlighted achievements in 3PM-guided IS management. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00376-2.

RESUMO

Although the xylose mutarotation and transformation have been investigated largely separately, their relationship has been rarely systematically elaborated. The effect of several factors such as xylose concentration, temperature, and salt concentration, affecting the mutarotation of xylose are discussed. Nine alkali halides (LiCl, NaCl, KCl, LiBr, NaBr, KBr, LiI, NaI, and KI) are used to test salt effects. The relationship between xylose rotation rate constant (kM), specific optical rotation at equilibrium ([α]eqm), α/ß ratio, H chemical shift difference (ΔΔδ), Gibbs free energy difference (ΔG), hydrogen ion or hydroxide ion concentration ([H+] or [OH-]), and xylose conversion is discussed. Different salts dissolved in water result in different pH of the solutions, which affect the mutarotation of xylose, with the nature of both cation and anion. Shortly, the smaller the cation radius is and the larger the anion radius is, the greater the mutarotation rate is. In the dehydration of xylose to furfural in salty solutions, xylose conversion is positively correlated to mutarotation rate, H+ or OH- concentration, and the energy difference between α-xylopyranose and ß-xylopyranose. Although the [α]eqm of xylose is positively correlated with α/ß configuration ratio, there is no obvious correlation with xylose dehydration. The conversion to furfural in chlorides is superior to that in bromines and iodides, which is due to the fact that the pH of chloride salts is smaller than that of the corresponding bromide and iodized salts. Higher H+ concentration prefers to accelerate the formation of furfural. In basic salt solutions, the xylulose selectivity is higher than that of furfural at the initial stage of reaction. The furfural selectivity and carbon balance are better in acidic condition rather than in basic condition. In H2O-MTHF (2-Methyltetrahydrofuran) biphasic system, the optimal furfural selectivity of 81.0 % is achieved at 190 °C in 1 h with the assistance of LiI and a little HCl (0.2 mmol, 8 mmol/L in aqueous phase). A high mutarotation rate represents rapid xylose conversion, but a high furfural selectivity prefers in acidic solutions, which would be perfect if organic solvents were available to form biphasic systems.

RESUMO

Hierarchical porous hypercrosslinked monoliths (PolyHIPE-HCP) with ultrahigh specific surface areas are prepared via a solvent knitting strategy. Compared to previous work, the solvent knitting strategy is carried out in a relatively low air-controlled atmosphere with gradient heating starting from low temperature while using DCM (Dichloromethane) as both a solvent and a cross-linker, allowing for a slow and controlled cross-linking process, thereby achieving a BET surface area ranging from 514 to 728 m2 g-1. Scanning electron microscopy (SEM) shows that the knitting process does not affect the presence of macroporous structure in the PolyHIPE. With the introduction of mesopores and micropores, these hierarchical porous monoliths exhibit significant potential for applications in gas adsorption and water treatment. Hence, a universal, simple and low-cost method to synthesize polymeric monoliths with hierarchically porous structure and higher surface area is proposed, which has fascinating prospects in industrialization.

RESUMO

Psoriatic arthritis (PsA) is an immune-mediated, chronic inflammatory joint disease that commonly occurs as a complication of psoriasis. EGF-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with multiple structural domains and associated with various physiological functions. In this study, we employed a mannan-induced psoriatic arthritis model to investigate the impact of EDIL3 on PsA pathogenesis. Notably, a downregulation of EDIL3 expression was observed in the PsA model, which correlated with increased disease severity. EDIL3 knockout mice exhibited a more severe phenotype of PsA, which was ameliorated upon re-infusion of recombinant EDIL3 protein. The mitigation effect of EDIL3 on PsA depends on its regulation of the activation of monocyte-derived DCs (MoDCs) and T-help 17 cells (Th17). After inhibiting the function of MoDCs and Th17 cells with neutralizing antibodies, the beneficial effects of EDIL3 on PsA were lost. By inducing adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppressing protein kinase B (AKT) phosphorylation, EDIL3 attenuates intracellular glycolysis in MoDCs stimulated by glucose, thereby impeding their maturation and differentiation. Moreover, it diminishes the differentiation of Th17 cells and decelerates the progression of PsA. In conclusion, our findings elucidate the role and mechanism of EDIL3 in the development of PsA, providing a new target for clinical diagnosis and treatment.

RESUMO

Cryptorchidism, commonly known as undescended testis, affects 1%-9% of male newborns, posing infertility and testis tumor risks. Despite its prevalence, the detailed pathophysiology underlying male infertility within cryptorchidism remains unclear. Here, we profile and analyze 46,644 single-cell transcriptomes from individual testicular cells obtained from adult males diagnosed with cryptorchidism and healthy controls. Spermatogenesis compromise in cryptorchidism links primarily to spermatogonium self-renewal and differentiation dysfunctions. We illuminate the involvement of testicular somatic cells, including immune cells, thereby unveiling the activation and degranulation of mast cells in cryptorchidism. Mast cells are identified as contributors to interstitial fibrosis via transforming growth factor ß1 (TGF-ß1) and cathepsin G secretion. Furthermore, significantly increased levels of secretory proteins indicate mast cell activation and testicular fibrosis in the seminal plasma of individuals with cryptorchidism compared to controls. These insights serve as valuable translational references, enriching our comprehension of testicular pathogenesis and informing more precise diagnosis and targeted therapeutic strategies for cryptorchidism.

Assuntos

Criptorquidismo , Perfilação da Expressão Gênica , Análise de Célula Única , Espermatogênese , Transcriptoma , Criptorquidismo/genética , Criptorquidismo/patologia , Criptorquidismo/metabolismo , Masculino , Humanos , Análise de Célula Única/métodos , Espermatogênese/genética , Transcriptoma/genética , Testículo/metabolismo , Testículo/patologia , Mastócitos/metabolismo , Mastócitos/patologia , Adulto , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Fibrose , Espermatogônias/metabolismo , Espermatogônias/patologia

RESUMO

Background/purpose: Quantitative in vitro research was conducted on the learning process of a dynamic navigation system. This study provides guidance for the promotion and application of dynamic navigation technology in the endodontic apical surgery field. Materials and methods: Standardized models were designed and 3D printed to form the approach operation of endodontic apical surgery. 6 clinicians with no experience in dynamic navigation performed the operation. The distance deviation tolerance was set as 0.6 mm, and the angle deviation tolerance was set as 5°. Fifteen mm deep approach operation was completed using dynamic navigation. Each operator performed 10 consecutive exercises on the models. The positioning deviation and operation time of each operator for each practice were recorded. Based on this, the learning curve of the dynamic navigation of every operator was mapped. The learning difficulty of dynamic navigation was evaluated. Results: The learning curves of all operators reached a stable level after the 7th practice, which can ensure that the distance and angle deviations are maintained within the deviation tolerances (0.6 mm, 5°). Conclusion: Operators with no experience in dynamic navigation technology need practice to master dynamic navigation operations. For this navigation system, operators with no operational experience can master dynamic navigation operations after 7 exercises.

RESUMO

BACKGROUND: Studies have shown that the ideal dose of epidural dexmedetomidine is 0.4 µg mL-1 for epidural labor analgesia. However, the appropriate dose of ropivacaine when combined with 0.4 µg mL-1 of dexmedetomidine for epidural labor analgesia is still unknown. Therefore, we aimed to determine the dose-response of ropivacaine when using 0.4 µg mL-1 of dexmedetomidine as epidural adjuvant for labor analgesia. METHODS: One hundred of nulliparous singleton pregnant patients were randomized allocated into 1 of 5 groups with epidural ropivacaine concentration of 0.05%, 0.0625%, 0.075%, 0.0875%, and 0.1%. Labor analgesia was initialed with 12 mL of the mixed study solution. Effective analgesia was defined as a visual analogue scale <10 mm 30 minutes after the initial epidural bolus. The EC50 and EC95 for epidural ropivacaine was calculated by probit regression. RESULTS: Ninety-three of parturients were involved into the final analysis. Totals of 63.2% (12/19), 73.7% (14/19), 88.9% (16/18), 94.7% (18/19), and 100% (18/18) of parturients in group 0.05, 0.0625, 0.075, 0.0875, and 0.1 received effective epidural labor analgesia. The calculated EC50 and EC95 of epidural ropivacaine were 0.046% (95% CI 0.028-0.054%) and 0.086% (95% CI 0.074-0.137%), respectively. CONCLUSIONS: Under the condition of the study, a bolus of 12 mL ropivacaine 0.086% and dexmedetomidine 0.4 µg mL-1 could afford 95% of nulliparous singleton pregnant patients without suffering labor pain after a test dose of lidocaine 45 mg.

Assuntos

Analgesia Epidural , Analgesia Obstétrica , Anestésicos Locais , Dexmedetomidina , Relação Dose-Resposta a Droga , Ropivacaina , Humanos , Feminino , Ropivacaina/administração & dosagem , Gravidez , Dexmedetomidina/administração & dosagem , Método Duplo-Cego , Adulto , Analgesia Epidural/métodos , Anestésicos Locais/administração & dosagem , Estudos Prospectivos , Analgesia Obstétrica/métodos , Analgésicos não Narcóticos/administração & dosagem , Medição da Dor , Dor do Parto/tratamento farmacológico , Adulto Jovem

RESUMO

PURPOSE: This study was designed to construct progressive binary classification models based on radiomics and deep learning to predict the presence of epidermal growth factor receptor (EGFR) and TP53 mutations and to assess the models' capacities to identify patients who are suitable for TKI-targeted therapy and those with poor prognoses. MATERIALS AND METHODS: A total of 267 patients with lung adenocarcinomas who underwent genetic testing and noncontrast chest computed tomography from our hospital were retrospectively included. Clinical information and imaging characteristics were gathered, and high-throughput feature acquisition on all defined regions of interest (ROIs) was carried out. We selected features and constructed clinical models, radiomics models, deep learning models, and ensemble models to predict EGFR status with all patients and TP53 status with EGFR-positive patients, respectively. The validity and reliability of each model were expressed as the area under the curve (AUC), sensitivity, specificity, accuracy, precision, and F1 score. RESULTS: We constructed 7 kinds of models for 2 different dichotomies, namely, the clinical model, the radiomics model, the DL model, the rad-clin model, the DL-clin model, the DL-rad model, and the DL-rad-clin model. For EGFR- and EGFR+, the DL-rad-clin model got the highest AUC value of 0.783 (95% CI: 0.677-0.889), followed by the rad-clin model, the DL-clin model, and the DL-rad model. In the group with an EGFR mutation, for TP53- and TP53+, the rad-clin model got the highest AUC value of 0.811 (95% CI: 0.651-0.972), followed by the DL-rad-clin model and the DL-rad model. CONCLUSION: Our progressive binary classification models based on radiomics and deep learning may provide a good reference and complement for the clinical identification of TKI responders and those with poor prognoses.

RESUMO

BACKGROUND AND OBJECTIVE: Motor Imagery (MI) recognition is one of the most critical decoding problems in brain- computer interface field. Combined with the steady-state somatosensory evoked potential (MI-SSSEP), this new paradigm can achieve higher recognition accuracy than the traditional MI paradigm. Typical algorithms do not fully consider the characteristics of MI-SSSEP signals. Developing an algorithm that fully captures the paradigm's characteristics to reduce false triggering rate is the new step in improving performance. METHODS: The idea to use complex signal task-related component analysis (cTRCA) algorithm for spatial filtering processing has been proposed in this paper according to the features of SSSEP signal. In this research, it's proved from the analysis of simulation signals that task-related component analysis (TRCA) as typical method is affected when the response between stimuli has reduced correlation and the proposed algorithm can effectively overcome this problem. The experimental data under the MI-SSSEP paradigm have been used to identify right-handed target tasks and three unique interference tasks are used to test the false triggering rate. cTRCA demonstrates superior performance as confirmed by the Wilcoxon signed-rank test. RESULTS: The recognition algorithm of cTRCA combined with mutual information-based best individual feature (MIBIF) and minimum distance to mean (MDM) can obtain AUC value up to 0.89, which is much higher than traditional algorithm common spatial pattern (CSP) combined with support vector machine (SVM) (the average AUC value is 0.77, p < 0.05). Compared to CSP+SVM, this algorithm model reduced the false triggering rate from 38.69 % to 20.74 % (p < 0.001). CONCLUSIONS: The research prove that TRCA is influenced by MI-SSSEP signals. The results further prove that the motor imagery task in the new paradigm MI-SSSEP causes the phase change in evoked potential. and the cTRCA algorithm based on such phase change is more suitable for this hybrid paradigm and more conducive to decoding the motor imagery task and reducing false triggering rate.

RESUMO

BACKGROUND: Type 2 diabetes, cardiovascular disease, and related cardiometabolic disturbances are increasing rapidly in the Asia-Pacific region. We investigated the contribution of excess adiposity, a key determinant of type 2 diabetes and cardiovascular risk, to unfavourable cardiometabolic profiles among Asian ethnic subgroups. METHODS: The Health for Life in Singapore (HELIOS) Study is a population-based cohort comprising multiethnic Asian men and women living in Singapore, aged 30-84 years. We performed a cross-sectional analysis of data from individuals who had assessment of body composition by dual-energy x-ray absorptiometry and metabolic characterisation. In a subset of participants on no medication for type 2 diabetes, hypertension, and hypercholesterolaemia, we tested the relationship of BMI and visceral fat mass index (vFMI) with cardiometabolic phenotypes (glycaemic indices, lipid levels, and blood pressure), disease outcomes (type 2 diabetes, hypercholesterolaemia, and hypertension), and metabolic syndrome score with multivariable regression analyses. FINDINGS: Between April 2, 2018, and Jan 28, 2022, 10 004 individuals consented to be part of the HELIOS cohort, of whom 9067 were included in the study (5404 [59·6%] female, 3663 [40·4%] male; 6224 [68·6%] Chinese, 1169 [12·9%] Malay, 1674 [18·5%] Indian; mean age 52·8 years [SD 11·8]). The prevalence of type 2 diabetes, hypercholesterolaemia, and hypertension was 8·2% (n=744), 27·2% (n=2469), and 18·0% (n=1630), respectively. Malay and Indian participants had 3-4-times higher odds of obesity and type 2 diabetes, and showed adverse metabolic and adiposity profiles, compared with Chinese participants. Excess adiposity was associated with adverse cardiometabolic health indices including type 2 diabetes (p<0·0001). However, while vFMI explained the differences in triglycerides and blood pressure between the Asian ethnic groups, increased vFMI did not explain higher glucose levels, reduced insulin sensitivity, and increased risk of type 2 diabetes among Indian participants. INTERPRETATION: Visceral adiposity is an independent risk factor for metabolic disease in Asian populations, and accounts for a large fraction of type 2 diabetes cases in each of the ethnic groups studied. However, the variation in insulin resistance and type 2 diabetes risk between Asian subgroups is not consistently explained by adiposity, indicating an important role for additional mechanisms underlying the susceptibility to cardiometabolic disease in Asian populations. FUNDING: Nanyang Technological University-the Lee Kong Chian School of Medicine, National Healthcare Group, and National Medical Research Council, Singapore.

Assuntos

Absorciometria de Fóton , Adiposidade , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Singapura/epidemiologia , Idoso , Adiposidade/fisiologia , Adulto , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Estudos Transversais , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etnologia , Obesidade/epidemiologia , Obesidade/etnologia , Obesidade/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etnologia , Hipertensão/epidemiologia , Hipertensão/etnologia , Estudos Epidemiológicos

RESUMO

BACKGROUND: Ambient particulate matter (PM) exposure is recognized as a risk factor for cardiovascular disease (CVD). However, the extent to which PM exposure is associated with CVD via triglyceride glucose (TyG)-related indicators remains unknown. This study examines the relationship between long-term PM exposure and CVD events, further assessing whether TyG-related indicators mediate this association. METHODS: This cohort study involved 7,532 individuals aged at least 45 years who were not diagnosed with CVD in 2011 from the China Longitudinal Study of Health and Retirement (CHARLS) and were followed up for the occurrence of CVD until 2020. The annual PM concentration data at the city level, with aerodynamic diameters ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10), were obtained from the ChinaHighAirPollutants (CHAP). The average concentration of PM in the 3 years before the baseline survey in 2011 was defined as the long-term exposure level of the individual. The relationship between PM exposure and CVD incidence was examined via Cox proportional hazards models, with a focus on probing the role of TyG-related indicators through mediation analysis. RESULTS: A total of 1,865 individuals with CVD were diagnosed over the span of a 7.4-year follow-up period. The 3-year average concentrations before baseline were 31.29 µg/m³ for PM1, 56.03 µg/m³ for PM2.5, and 95.73 µg/m³ for PM10. In fully adjusted model, the Cox proportional hazards models revealed that an increase of 10 µg/m³ in the PM1, PM2.5, and PM10 exposure concentrations corresponded to elevated CVD risk, with HRs (95% CI) of 1.135 (1.078-1.195), 1.092 (1.062-1.123), and 1.075 (1.059-1.090), respectively. Mediation analyses further suggested that the correlation between PM exposure and CVD could be partly mediated via TyG-BMI, TyG-WC, and TyG-WHtR, with mediation proportions varying from 5.54 to 15.30%. CONCLUSION: A significant correlation was observed between long-term PM exposure and increased CVD risk, with TyG-related indicators, such as TyG-BMI, TyG-WC, and TyG-WHtR, partially mediating this relationship.

Assuntos

Doenças Cardiovasculares , Exposição Ambiental , Material Particulado , Triglicerídeos , Humanos , Material Particulado/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Masculino , Feminino , Estudos Longitudinais , Pessoa de Meia-Idade , Idoso , China/epidemiologia , Triglicerídeos/sangue , Exposição Ambiental/efeitos adversos , Modelos de Riscos Proporcionais , Fatores de Risco , Glicemia/metabolismo , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos

RESUMO

Epithelial ovarian cancer is the deadliest gynecologic malignancy, characterized by high metastasis. Transforming growth factor-ß1 (TGF-ß1) drives epithelial- mesenchymal transformation (EMT), a key process in tumor metastasis. Tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) acts as a negative regulator of innate and adaptive immunity and involves in various cancers. However, its relationship with TGF-ß1 in ovarian cancer and its role in reversing TGF-ß1-induced EMT remain unclear. This study examined TIPE2 mRNA and protein expression using quantitative RT-PCR (qRT-PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of epithelial ovarian cancer cells were assessed through 5-ethynyl-2-deoxyuridine, colony-forming, transwell migration and invasion assays. The relationship between TIPE2 and TGF-ß1 was investigated using qRT-PCR and enzyme-linked immunosorbent assay, while the interaction between TIPE2 and Smad2 was identified via co-immunoprecipitation. The results revealed that TIPE2 protein was significantly down-regulated in epithelial ovarian cancer tissues and correlated with the pathological type of tumor, patients' age, tumor differentiation degree and FIGO stage. TIPE2 and TGF-ß1 appeared to play an opposite role to each other during the progression of human ovarian cancer cells. Furthermore, TIPE2 inhibited the metastasis and EMT of ovarian cancer cells by combining with Smad2 in vitro or in an intraperitoneal metastasis model. Consequently, these findings suggest that TIPE2 plays a crucial inhibitory role in ovarian cancer metastasis by modulating the TGF-ß1/Smad2/EMT signaling pathway and may serve as a potential target for ovarian cancer, providing important direction for future diagnostic and therapeutic strategies.

Assuntos

Carcinoma Epitelial do Ovário , Movimento Celular , Transição Epitelial-Mesenquimal , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Ovarianas , Proteína Smad2 , Fator de Crescimento Transformador beta1 , Proteína Smad2/metabolismo , Proteína Smad2/genética , Humanos , Feminino , Fator de Crescimento Transformador beta1/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/genética , Linhagem Celular Tumoral , Animais , Camundongos , Invasividade Neoplásica , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Camundongos Endogâmicos BALB C , Transdução de Sinais

RESUMO

A disease called "hydrosalpinx fluid and egg drop syndrome" (HFEDS) was observed in four flocks of Jinding ducks (Anas platyrhynchos domesticus) in Northeast China during the years 2022 to 2023. Here, we investigated the possible involvement of avian metapneumovirus (AMPV) infection. Full-length genome sequencing and sequence analysis of two AMPV strains showed that they belong to Eurasian lineage of AMPV subtype C. Based on surface glycoprotein (G) sequence comparisons, the Eurasian lineage can be divided into two sublineages (E1 and E2), and sublineage E2 is circulating in Jinding duck populations in Northeast China.

Assuntos

Patos , Genoma Viral , Metapneumovirus , Infecções por Paramyxoviridae , Filogenia , Doenças das Aves Domésticas , Animais , Patos/virologia , Metapneumovirus/genética , Metapneumovirus/classificação , Metapneumovirus/isolamento & purificação , Doenças das Aves Domésticas/virologia , Infecções por Paramyxoviridae/veterinária , Infecções por Paramyxoviridae/virologia , China , Genoma Viral/genética , Sequenciamento Completo do Genoma

RESUMO

Objective: To assess the effects of in-bed cycling (IBC) combined with high flow nasal cannula (HFNC) on arterial oxygen and respiratory dynamics in patients with severe respiratory failure (RF). Methods: We retrospectively collected clinical data of 103 patients with severe RF, admitted to the intensive care unit (ICU) of The Second Affiliated Hospital of Harbin Medical University from March 2021 to March 2023. Among them, 50 patients had HFNC alone (control group), and 53 patients did IBC in addition to HFNC (observation group). We compared arterial oxygen index, lung function, respiratory dynamics, and clinical efficacy between the two groups. Results: There was no significant difference in the basic data between the two groups (P>0.05). After the treatment, the improvement of the partial pressure of oxygen (PaO2), PaO2/fraction of inspired oxygen (FiO2), arterial oxygen saturation (SaO2), and oxygen delivery (DO2) in the observation group was significantly better than that in the control group (P<0.05). After the treatment, the improvement of lung function in the observation group was better than that in the control group (P<0.05). After the treatment, the end expiratory pulmonary pressure (Ptp-ee) and driving pressure (△Ptp) levels in the observation group were significantly higher, and the duration of ICU hospitalization and the incidence of ICU-acquired weakness(ICU-AW) were significantly lower than those in the control group (P<0.05). Conclusions: IBC combined with HFNC can significantly improve arterial oxygen levels, lung function, and respiratory dynamics in patients with severe RF. IBC in combination with HFNC is associated with shorter stay time in the ICU, reduced of ICU-acquired weakness, and better physical recovery of patients.

RESUMO

BACKGROUND: Wheat is an important grain crop that has been under serious threat from Fusarium graminearum. Nup2, a member of the nuclear pore complex, plays an important role in regulating eukaryotic nuclear protein transport and participates in gene regulation. Dissecting the function of nuclear pore proteins in pathogenic fungi may provide effective targets for novel fungicides. RESULTS: Mutants exhibited nutritional growth defects, asexual/sexual developmental abnormalities. Deficiency of FgNup2 resulted in increased resistance of Fusarium graminearum to cell wall disruptors and increased sensitivity to metal ions. Pathogenicity analyses showed that the mutant was significantly less virulent on flowering wheat ears, consistent with the observed decrease in deoxynivalenol (DON) production. Furthermore, we showed that FgNup2 interacts synergistically with FgTri6, a transcription factor of the TRI family, to regulate the expression of toxin-producing genes, which, in turn, affects the biosynthesis of DON and related toxins. CONCLUSION: This study revealed that FgNup2 plays important roles in the growth and development, cell wall integrity, stress response, pathogenicity, and DON synthesis of F. graminearum. © 2024 Society of Chemical Industry.