The characteristics of intratumoral microbial community reflect the development of lung adenocarcinoma.

Introduction: An increasing number of studies have demonstrated the pivotal role of microbiota changes in the onset, progression, diagnosis, treatment, and prognosis of lung adenocarcinoma (LUAD). However, a comprehensive analysis of intratumoral microbiome variation across distinct LUAD stages has not been performed. The aim of this study was to identify the microbial markers that significantly vary during tumor stage of LUAD. Methods: Here, we used the cancer genome atlas (TCGA) database to comprehensively compare and analyze the differences in microbial composition between 267 patients with early and 224 patients with advanced LUAD. In order to determine the best biomarkers, we used the random forest (RF) model and found that the microbial markers have a certain ability in predicting the stage of LUAD. Results: We found that there were certain differences in the microbiome of patients with LUAD at different stages, especially in the tumor tissues of patients with advanced LUAD, whose co-abundance network was significantly more complex. We also found that five bacterial biomarkers (Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, Loktanella, and Serratia) were correlated with LUAD stage, among which Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, and Serratia were significantly overexpressed in patients with advanced LUAD. In particular, after integrating the biomarkers of mRNA, we achieved an area under the curve (AUC) of 0.70. Discussion: Our study revealed the microbial profile of patients with LUAD and the intrinsic pathogenic mechanism between the microbiome and the disease, and established a multi-omics model to determine LUAD tumor stage.

Sunlight-driven and gram-scale vanillin production via Mn-defected γ-MnO2 catalyst in aqueous environment.

The production of vanillin from biomass offers a sustainable route for synthesizing daily-use chemicals. However, achieving sunlight-driven vanillin synthesis through H2O activation in an aqueous environment poses challenges due to the high barrier of H2O dissociation. In this study, we have successfully developed an efficient approach for gram-scale vanillin synthesis in an aqueous reaction, employing Mn-defected γ-MnO2 as a photocatalyst at room temperature. Density functional theory calculations reveal that the presence of defective Mn species (Mn3+) significantly enhances the adsorption of vanillyl alcohol and H2O onto the surface of the γ-MnO2 catalyst. Hydroxyl radical (˙OH) species are formed through H2O activation with the assistance of sunlight, playing a pivotal role as oxygen-reactive species in the oxidation of vanillyl alcohol into vanillin. The Mn-defected γ-MnO2 catalyst exhibits exceptional performance, achieving up to 93.4% conversion of vanillyl alcohol and 95.7% selectivity of vanillin under sunlight. Notably, even in a laboratory setting during the daytime, the Mn-defected γ-MnO2 catalyst demonstrates significantly higher catalytic performance compared to the dark environment. This work presents a highly effective and promising strategy for low-cost and environmentally benign vanillin synthesis.

An online survey on public awareness of drug clinical trials in inland cities of northern China.

Objective: The aims of this survey were to investigate the public awareness of drug clinical trials (DCTs) and willingness to participate the DCTs, and provide references for propaganda and science popularization of DCTs. Methods: A self-designed questionnaire named "an online survey questionnaire on public awareness of DCTs" was used to conduct an online survey from January to March 2022. The demographic characteristics and the response of participants to the awareness and willingness to participate the DCTs were collected. The factors affecting the public awareness of DCTs were analyzed by single factor and binary logistic regression analysis. Results: One thousand three hundred eighty valid questionnaires were collected, and the respondents' awareness rate of DCTs was 61.1%. Thirteen demographic characteristics including age, gender, education, occupation, work fields, household type, marital status, city type, income, medical insurance, medical expenditure, pressure to seek medical care, financial pressure, both significantly affected the qualified rate of participants' awareness of DCTs (p < 0.001) by single factor analysis. Binary logistic regression analysis indicated that education level, work fields, city type, medical insurance, and medical expenditure affected independently the participants' awareness rate of DCTs (p < 0.001). 52.9% of the participants were willing to take part in DCTs. "to promote medical progress" (54.4%) or "believe doctors" (31.1%) were the most frequent reasons for subjects participating in DCTs. Conclusion: The public awareness rate of DCTs and the willingness to participate in drug clinical were significantly affected by the demographic characteristics of subjects. Thus, targeting the needs of the public, propaganda, and science popularization of DCTs should be carried out and served public health.

Dietary inflammatory index is associated with severe depression in older adults with stroke: a cross-sectional study.

Inflammation is involved in the pathogenesis of stroke and depression. We aimed to investigate the association between the dietary inflammatory index (DII) and depression in American adults with stroke. Adults with stroke were enrolled from the National Health and Nutrition Examination Survey between 2005 and 2018 in the United States. The DII was obtained from a 24-h dietary recall interview for each individual. Multivariate regression and restricted cubic spline analyses were conducted to evaluate the association between DII and depression in adults with stroke. The mean age of the 1,239 participants was 63.85 years (50.20% women), and the prevalence of depression was 18.26%. DII showed a linear and positive association with severe depression in adults with stroke (OR, 1.359; 95% CI, 1.021, 1.810; p for non-linearity=0.493). Compared with those in the lowest tertile of the DII, adults with stroke in the third tertile of the DII had a 3.222-fold higher risk of severe depression (OR, 3.222; 95% CI, 1.150, 9.026). In the stratified analyses, the association between DII score and severe depression was more significant in older adults (p for interaction=0.010) but not significant with respect to sex (p for interaction=0.184) or smoking status (p for interaction=0.396). No significant association was found between DII and moderate-to-moderately severe depression in adults with stroke. In conclusion, an increase in DII score was associated with a higher likelihood of severe depression in older adults with stroke.

Enhancing Concrete Mechanical Properties through Basalt Fibers and Calcium Sulfate Whiskers: Optimizing Compressive Strength, Elasticity, and Pore Structure.

To study the effects of basalt fibers (BFs), calcium sulfate whiskers (CSWs), and modified calcium sulfate whiskers (MCSWs) on the compressive strength and dynamic modulus of elasticity of concrete, this paper utilizes Mercury Intrusion Porosimetry (MIP) to measure the microstructure of concrete and calculate the fractal dimension of pore surface area. The results indicate that both CSWs and BFs can increase the compressive strength of concrete. CSWs can enhance the dynamic modulus of elasticity of concrete, while the effect of BFs on the dynamic modulus of elasticity is not significant. The improvement in compressive strength and dynamic modulus of elasticity provided by MCSWs is significantly greater than that provided by CSWs. Both CSWs and BFs can effectively improve the pore structure of concrete and have a significant impact on the surface fractal dimension. CSWs inhibit the formation of ink-bottle pores, while BFs increase the number of ink-bottle pores. Due to the ink-bottle pore effect, the fractal dimension of the capillary pore surface is generally greater than three, lacking fractal characteristics. The compressive strength and dynamic modulus of elasticity of concrete have a good correlation with the fractal dimensions of large pores and transition pores.

Analysis of potential volatile organic compounds in Sitophilus zeamais (Coleoptera: Curculionidae)-infested wheat based on lipid oxidation-a reference to early and rapid detection method.

The maize weevil, Sitophilus zeamais Motschulsky, is a hidden pest that presents serious risk to grain quality during postharvest storage. Lipid-derived volatile detection is considered a key reference for early prediction of S. zeamais infestation. However, the exact compositions of fatty acids and volatile organic compounds (VOCs) in S. zeamais-infested wheat are yet to be determined. In this study, we aimed to explore the effect of S. zeamais infestation on lipid metabolism in wheat infested with S. zeamais eggs (4 days), larvae (20 days), pupae (35 days), and adults (45 days). Compared to those in the control group, the activities of lipid oxidation enzymes, such as lipase, lipoxygenase, and alcohol dehydrogenase, increased by 82.73%, 105.12%, and 487.86%, respectively, during the storage period of 1 life cycle of S. zeamais. Additionally, the fatty acid composition of S. zeamais-infested wheat was significantly altered (palmitic acid [1.10-fold], oleic acid [1.07-fold], and linoleic acid [0.95-fold]). Furthermore, 91 VOCs were identified in all wheat samples; then, multivariate statistical analyses categorized these samples into 4 groups: uninfested, longer storage, lightly infested, and heavily infested. Moreover, 31, 26, and 45 potential VOCs were identified to distinguish uninfested wheat from those in the other 3 groups. These results demonstrated that S. zeamais infestation induces an elevation in lipid-related enzymatic activities, which potentially leads to a decrease in lipid content alongside the production of specific VOCs (undecan-4-olide, heptaldehyde, and 2-nonenal). These findings provide novel insights for rapidly identifying grains infested by hidden pests and effectively managing these pests during grain storage.

Lysyl oxidase-mediated elastin upregulation promotes the proliferation and migration of human retinal endothelial cells.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is a major cause of irreversible blindness in the working age population. The dysfunction of retinal vascular endothelial cells (RVECs) is the primary cause of PDR. Extracellular matrix (ECM) accumulation promotes intracellular signaling required for RVEC proliferation, migration, survival, and tube morphogenesis. OBJECTIVES: This study aimed to investigate the role of lysyl oxidase (LOX) in the cellular function of RVECs and PDR pathogenesis and to identify the underlying mechanisms. MATERIAL AND METHODS: Protein expression was determined with western blot. The interaction between LOX and elastin (ELN) was detected using a co-immunoprecipitation (Co-IP) assay, and the Cell Counting Kit-8 (CCK-8) assay evaluated cell viability. A colony formation assay was employed to assess the proliferation of human RVECs (hRVECs), and a transwell assay to determine their migration ability. Streptozotocin was used to establish PDR in mice in vivo. A histological analysis was conducted using hematoxylin and eosin (H&E) staining. RESULTS: The results showed that LOX was overexpressed in PDR patients. The LOX knockdown suppressed ECM formation and hRVEC proliferation and migration. Additionally, LOX upregulated ELN expression. However, overexpressed ELN promoted hRVEC proliferation and migration. In vivo experiments showed that curcumin-mediated LOX deficiency restored retinal tissue structure. CONCLUSIONS: The LOX-knockdown suppressed ECM formation and hRVEC proliferation and migration by inactivating ELN. Therefore, LOX/ELN signaling may be a potential PDR biomarker.

Association of serum uric acid with women's ovarian reserve: observational study and Mendelian randomization analyses.

OBJECTIVE: To investigate the association between serum uric acid and women's ovarian reserve. DESIGN: Retrospective observational study and Mendelian randomization study. SETTING: University-affiliated in vitro fertilization center. PATIENTS: Observational analyses were undertaken using data from 8,257 women with infertility who finished their first in vitro fertilization treatments between May 2017 and December 2021. Mendelian randomization analyses were based on genome-wide association summary statistics from several biobanks of predominantly European ancestries. INTERVENTIONS: Observational study involved testing log2 transformed serum uric acid levels (for linear, negative regression, and logistic regression analyses); original uric acid levels (for nonlinear association analyses). Mendelian randomization study involved testing genetically predicted uric acid levels. MAIN OUTCOME MEASURES: Biomarkers including antimüllerian hormone, basal antral follicle count, follicle-stimulating hormone, luteinizing hormone, ratio of follicle-stimulating hormone to luteinizing hormone, estradiol; indices of ovarian response to stimulation including poor ovarian response according to different criteria and oocyte yield. RESULTS: In retrospective observational study, all ovarian reserve-related outcomes demonstrated significant differences across serum uric acid quartiles. A two-fold uric acid increase was associated with increased antimüllerian hormone (adjusted ß = 0.69; 95% confidence interval [CI], 0.43-0.95), antral follicle count (adjusted incidence rate ratio = 1.10, 95% CI, 1.05-1.14), luteinizing hormone (adjusted ß = 0.53, 95% CI, 0.28-0.78), decreased risks of Bologna poor ovarian response (adjusted odds ratio = 0.97; 95% CI, 0.95-0.99) and groups 2-4 Poseidon poor ovarian response (group 2: 0.63, 0.56-0.71; group 3: 0.71, 0.65-0.78; group 4: 0.50, 0.46-0.55), whereas an increased risk of group 1 (1.26, 1.13-1.41). Nonlinear analyses showed a common inflection point at 320-340 µmol/L of uric acid. Interactions between uric acid and antimüllerian hormone and antral follicle count were presented in association with oocyte yield. Mendelian randomization results suggested a significant association between genetically predicted uric acid levels and antimüllerian hormone levels (ß = 0.08; 95% CI, 0.04-0.12) but none for uric acid in relation to polycystic ovarian syndrome or other related hormones. CONCLUSION: Higher uric acid levels were associated with better ovarian reserve and increased levels of antimüllerian hormone albeit an increased risk of unexpected poor ovarian response.

Rapid discrimination of urine specific gravity using spectroscopy and a modified combination method based on SPA and spectral index.

To achieve high-accuracy urine specific gravity discrimination and guide the design of four-waveband multispectral sensors. A modified combination strategy was attempted to be proposed based on the successive projections algorithm (SPA) and the spectral index (SI) in the present study. First, the SPA was used to select four spectral variables in the full spectra. Second, the four spectral variables were mathematically transformed by SI to obtain SI values. Then, SPA gradually fusions the SI values and establishes models to identify USG. The results showed that the SPA can screen out the four characteristic wavelengths related to the measured sample attributes. SIs can be used to improve the performance of constructed prediction models. The best model only involves four spectral variables and 1 SI value, with high accuracy (91.62%), sensitivity (0.9051), and specificity (0.9667). The results reveal that m-SPA-SI can effectively distinguish USG and provide design guidance for 4-wavelength multispectral sensors.

Pt@AuNF nanozyme and horseradish peroxidase-based lateral flow immunoassay dual enzymes signal amplification strategy for sensitive detection of zearalenone.

Lateral flow immunoassay (LFIA) has been employed extensively for the rapid, accurate, and portable detection of foodborne toxins. Here, the platinum gold nanoflower core-shell (Pt@AuNF) nanozyme with excellent optical properties, good catalytic ability and controllable reaction conditions were prepared to effectively improve the performance of lateral flow immunoassay (LFIA) strips. The Pt@AuNF nanozyme and horseradish peroxidase (HRP) combined with monoclonal antibody were used as signal probes based on the dual enzymes catalytic signal amplification strategy to detect Zearalenone sensitively. Dual enzymes catalyze the decomposition of hydrogen peroxide into hydroxyl radicals, and under the influence of hydroxyl radicals, colorless 3,3',5,5' -tetramethylbenzidine (TMB) is oxidized to blue ox-TMB, which is superimposed on the strips for signal amplification to broaden the detection range. The limit of detection (LOD) of the Pt@AuNF-HRP labeled LFIA strips after signal amplification was 0.052 ng/mL, and the detection range was 0.052-7.21 ng/mL. Compared with the Pt@AuNF labeled strips, while reducing the probes amount by half to achieve antibody conservation, the detection range was expanded by 5-fold based on achieving improved sensitivity. The study provided a meaningful reference for expanding the detection range based on immunoassay.

Integration of single-cell and bulk RNA-sequencing to analyze the heterogeneity of hepatocellular carcinoma and establish a prognostic model.

BACKGROUND: The highly heterogeneous nature of hepatocellular carcinoma (HCC) results in different responses and prognoses to the same treatment in patients with similar clinical stages. AIMS: Thus, it is imperative to investigate the association between HCC tumor heterogeneity and treatment response and prognosis. METHODS AND RESULTS: At first, we downloaded scRNA-seq, bulk RNA-seq, and clinical data from TCGA and GEO databases. We conducted quality control, normalization using SCTransform, dimensionality reduction using PCA, batch effect removal using Harmony, dimensionality reduction using UMAP, and cell annotation-based marker genes on the scRNA-seq data. We recognized tumor cells, identified tumor-related genes (TRGs), and performed cell communication analysis. Next, we developed a prognostic model using univariable Cox, LASSO, and multivariate Cox analyses. The signature was evaluated using survival analysis, ROC curves, C-index, and nomogram. Last, we studied the predictability of the signature in terms of prognosis and immunotherapeutic response for HCC, assessed a variety of drugs for clinical treatment, and used the qRT-PCR analysis to validate the mRNA expression levels of prognostic TRGs. CONCLUSION: To conclude, this study expounded upon the influence of tumor cell heterogeneity on the prediction of treatment outcomes and prognosis in HCC. This, in turn, enhances the predictive ability of the TNM staging system and furnishes novel perspectives on the prognostic assessment and therapy of HCC.

Automatic MDSPE Combined with DART-HRMS for the Rapid Quantitation of 21 Synthetic Cathinones in Urine.

A new, rapid, and automated method for the quantitation of 21 synthetic cathinones in urine was established using magnetic dispersive solid-phase extraction (MDSPE) in combination with direct analysis in real time-high-resolution mass spectrometry (DART-HRMS). Sample preparation and quantitation were verified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methcathinone-D3, α-PVP-D8, and proadifen (SKF525A) were used as internal standards. Magnetic HLB extractant and NaH2PO4/NaOH buffer (0.2 M, pH 7) were used in automatic MDSPE. All 21 synthetic cathinones could be detected and analyzed by DART-HRMS in under 1 min. It was proven that the linearities of 21 synthetic cathinones were suitable (R2 > 0.99) in the concentration ranges of 0.5-100 ng/mL or 1-100 ng/mL. The precision and accuracy values were all within ±15%, and the samples were stable under various conditions. The average time of each sample from preprocessing to completion of detection was approximately 2 min, allowing for rapid sample analysis. The relative error (RE) of the concentrations obtained by DART-HRMS and LC-MS/MS were within ±13.61%, and the linear coefficient (R) was 0.9964. The results of DART-HRMS and LC-MS/MS provided equivalent values at the 95% confidence level. In summary, a simple, fast, and convenient quantitation method via DART-HRMS was established. This application can be utilized to reduce backlogs and promote rapid case processing.

Effects of zinc oxide nanocomposites on microorganism growth and protection of physicochemical quality during maize storage.

Maize moldy and spoilage due to microbial growth is a significant challenge in grain storage. This study aimed to evaluate the effectiveness of a zinc oxide nanocomposite, ZnO@mSiO2, prepared in our previous research, in inhibiting mold growth and preserving maize cell quality. The results demonstrated that ZnO@mSiO2 could effectively inhibit the growth of dominant microorganism, Aspergillus flavus, Talaromyces variabilis, Penicillium citrinum and Fusarium graminearum, in maize storage. Aspergillus flavus was selected as the model fungus, ZnO@mSiO2 effectively disrupted fungal hyphae structure, leading to reduced hyphal mass and inhibited spore germination. The inhibitory effect of ZnO@mSiO2 on mold growth was concentration-dependent. However, the ZnO@mSiO2 at an appropriate concentration (not exceeding 3.0 g/kg) preserved the integrity of maize cell membranes and enhancing the antioxidant activity within maize cells. The findings highlight the potential of ZnO@mSiO2 as an effective protectant to inhibit mold growth and preserve maize quality during storage.

[Characteristics of Soil Pollution and Source Analysis of Typical Pollutants in the Petrochemical Site].

Taking the soil of a petrochemical site in Chongqing as the research object, the pollution sources of heavy metals and volatile organic pollutants in the study area were quantitatively analyzed using principal component analysis and a positive definite matrix decomposition model. The research results showed that:① the average values of Cd, Cu, Pb, Hg, and Mn in the soil of the petrochemical site and its surrounding areas were higher than the soil background values in Chongqing, and the content of Co in 6% of sampling points was higher than the risk screening value of the first type of land use for construction land(GB 36600-2018). The pollution level of Hg, Mn, chloroform, ethylbenzene, m/p-xylene, and o-xylene in the soil of the site was more serious than that of the soil around the site. The industrial production activities of the site will cause significant pollution to the soil of the site. ② Eight heavy metals in the soil could be classified into four sources:62.50% Cd, 54.53% Ni, 54.12% Cu, 51.26% Co, 49.34% Pb, and 31.80% Hg were from the mixed sources of industrial emissions and agricultural activities. A total of 47.61% Mn was from the mixed source of natural and raw material production activities; 62.79% Hg, 21.57% As, 19.43% Mn, and 18.42% Cd were from the emission of coal-fired industrial activities; and 78.01% As, 46% Pb, 39.94% Cu, 38.15% Ni, 36.49% Co, 26.12% Mn, and 14.29% Cd were from the original material soil. ③ Seven volatile organic compounds in the soil of the site were mainly classified into three types of sources:86.49% dichloromethane and 90.14% tetrachloroethylene were from human activities in petrochemical sites; 98.88% m/p-xylene, 96.28% o-xylene, 84.62% ethylbenzene, and 76.46% toluene were from petrochemical site pollutant leakage sources; and 80.24% chloroform was from the natural sources.

An Overview of Traditional Chinese Medicine in the Treatment After Radical Resection of Hepatocellular Carcinoma.

According to the Barcelona Clinic Liver Cancer (BCLC) system, radical resection of early stage primary hepatocellular carcinoma (HCC) mainly includes liver transplantation, surgical resection, and radiofrequency ablation (RFA), which yield 5-year survival rates of about 70-79%, 41.3-69.5%, and 40-70%, respectively. The tumor-free 5-year rate for HCC patients undergoing radical resection only reach up to 13.7 months, so the prevention of recurrence after radical resection of HCC is very important for the prognosis of patients. The traditional Chinese medicine (TCM) takes the approach of multitarget and overall-regulation to treat tumors, it can also independently present the "component-target-pathway" related to a particular disease, and its systematic and holistic characteristics can provide a personalized therapy based on symptoms of the patient by treating the patient as a whole. TCM as postoperative adjuvant therapy after radical resection of HCC in Barcelona Clinic liver cancer A or B stages, and the numerous clinical trials confirmed that the efficacy of TCM in the field of HCC has a significant effect, not only improving the prognosis and quality of life but also enhancing patient survival rate. However, with the characteristics of multi-target, multi-component, and multi-pathway, the specific mechanism of Chinese medicine in the treatment of diseases is still unclear. Because of the positive pharmacological activities of TCM in combating anti-tumors, the mechanism studies of TCM have demonstrated beneficial effects on the regulation of immune function, chronic inflammation, the proliferation and metastasis of liver cancer cells, autophagy, and cell signaling pathways related to liver cancer. Therefore, this article reviews the mechanism of traditional Chinese medicine in reducing the recurrence rate of HCC after radical resection.

Associations between homocysteine, vitamin B12, and folate and the risk of all-cause mortality in American adults with stroke.

Objective: Associations between plasma homocysteine (Hcy), vitamin B12, and folate and the risk of all-cause mortality are unclear. This study aimed to examine whether plasma Hcy, vitamin B12, and folate levels independently predict the risk of all-cause mortality in American adults with stroke. Methods: Data from the United States National Health and Examination Survey (NHANES; 1999-2006) were used and linked with the latest (2019) National Death Index (NDI). Cox proportional hazards models and restricted cubic splines were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of all-cause mortality for Hcy, folate, and B12 levels in adults with stroke. Sample weights were calculated to ensure the generalizability of the results. Results: A total of 431 participants were included (average age: 64.8 years). During a median follow-up of 10.4 years, 316 deaths occurred. Hcy was positively associated with all-cause mortality in adults with stroke (HR, 1.053; 95% CI: 1.026-1.080). Stroke patients with plasma Hcy levels in the fourth quartile had a 1.631-fold higher risk of all-cause mortality (HR, 1.631; 95% CI: 1.160-2.291) than those in the first quartile. The association between plasma Hcy and all-cause mortality was strong significant in older patients (p for interaction = 0.020). Plasma folate and vitamin B12 concentrations were inversely correlated with Hcy concentrations [B-value (95% CI): -0.032 (-0.056- -0.008), -0.004 (-0.007- -0.002), respectively]. No significant associations were observed between folate, vitamin B12 levels, and all-cause mortality in adults with stroke. Conclusion: Plasma Hcy levels were positively associated with all-cause mortality in older adults with stroke. Folate and vitamin B12 levels were inversely correlated with Hcy. Plasma Hcy may serve as a useful predictor in mortality risk assessment and targeted intervention in adults with stroke.

Upregulation of eIF2α by m6A modification accelerates the proliferation of pulmonary artery smooth muscle cells in MCT-induced pulmonary arterial hypertension rats.

Pulmonary arterial hypertension (PAH) is a malignant cardiovascular disease. Eukaryotic initiation factor 2α (eIF2α) plays an important role in the proliferation of pulmonary artery smooth muscle cells (PASMCs) in hypoxia-induced pulmonary hypertension (HPH) rats. However, the regulatory mechanism of eIF2α remains poorly understood in PAH rats. Here, we discover eIF2α is markedly upregulated in monocrotaline (MCT)-induced PAH rats, eIF2α can be upregulated by mRNA methylation, and upregulated eIF2α can promote PASMC proliferation in MCT-PAH rats. GSK2606414, eIF2α inhibitor, can downregulate the expression of eIF2α and alleviate PASMC proliferation in MCT-PAH rats. And we further discover the mRNA of eIF2α has a common sequence with N 6-methyladenosine (m6A) modification by bioinformatics analysis, and the expression of METTL3, WTAP, and YTHDF1 is upregulated in MCT-PAH rats. These findings suggest a potentially novel mechanism by which eIF2α is upregulated by m6A modification in MCT-PAH rats, which is involved in the pathogenesis of PAH.

Subclinical damage to the contralateral eye in unilateral optic neuritis: A longitudinal study.

BACKGROUND: Early detection of subclinical injuries can lead to a correct diagnosis and help control the advancement of the condition. This study aims to investigate the presence of subclinical damage and silent progression to the contralateral eye's visual function and structure in patients experiencing their first episode of unilateral optic neuritis (ON). METHODS: Fifty patients with first-onset unilateral ON were enrolled in this study. Based on etiology, they were classified as having neuromyelitis optica spectrum disorder-related ON (NMOSD-ON), myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON), idiopathic ON (IDON), or multiple sclerosis-related ON (MS-ON). These cases were followed up for one year to determine whether there was any silent progression of visual function and structure in the contralateral non-ON (NON) eye. A gender- and age-matched healthy control (HC) group was included to compare the differences in visual function and structure between the patients with NON eyes and the HC group. RESULTS: Within two weeks of onset, best-corrected visual acuity (BCVA; P = 0.008), mean deviation (MD) of the visual field (VF) (P = 0.001), and peripapillary retinal nerve fiber layer (pRNFL; P = 0.019) thickness were significantly worse in the NMOSD-NON patients than those in the HC group, while there were no differences in the pRNFL and the ganglion cell-inner plexiform layer (GCIPL) thicknesses and quadrant thicknesses (P > 0.05) of the groups. IDON-NON only showed subclinical damage in VF (P = 0.001) and temporal pRNFL (P = 0.042), while the BCVA, VF, and optic nerve structure (pRNFL, GCIPL) of the MOG-NON patients showed no subclinical damage (P > 0.05). In addition, the one-year follow-up of each NON eye type showed that there was no silent progression in NMOSD-NON, MOG-NON, or IDON-NON. A pairwise comparison of the different types of NON eyes revealed no statistical differences (P > 0.05). CONCLUSION: Among the patients with unilateral ON, NMOSD-NON and IDON-NON resulted in subclinical damage to the visual function and structure of the contralateral eye within two weeks of onset, whereas MOG-NON did not show any subclinical damage to visual function or structure. Furthermore, these subclinical damages did not show any silent progression during the one-year follow-up period.

Associations between homocysteine and B vitamins and stroke: a cross-sectional study.

Objective: Homocysteine (Hcy) is a predictor for stroke. B vitamins are required for the metabolism of Hcy. We designed a study to investigate the associations of plasma Hcy and B vitamins with the prevalence of stroke in adults. Methods: A total of 8,371 adults were included in the National Health and Examination Survey (NHANES) between 2003-2006 in the United States. Multivariate regression analysis and smooth curve fitting were conducted to evaluate the associations of stroke prevalence with Hcy, folate, vitamin B6, and B12. A segmented regression model was used to analyze the threshold effects. Sample weights were calculated to ensure the results' generalizability. Results: The mean age of all participants was 46.43 years (51.8% women), and the prevalence of stroke was 2.72%. A nonlinear and positive association was found between plasma Hcy levels and the prevalence of stroke. Furthermore, L-shaped associations were found between plasma vitamin B6 and folate levels and stroke, with the turning point at 65.2 nmol/L for vitamin B6 and 26 nmol/L for folate, respectively. Vitamin B12 revealed a U-shaped relationship with stroke, with the turning points at 492.98 pmol/L for vitamin B12. Conclusion: Non-linear associations of plasma Hcy and B vitamins levels with stroke prevalence were found in American adults. These associations may have an implication that higher plasma Hcy levels should be reduced, and plasma vitamin B6, vitamin B12 and folate levels should be moderately improved in stroke prevention. Future studies are needed to verify the causality of these associations and elucidate the underlying mechanisms.