Methane (CH4) is the second most consequential greenhouse gas after CO2, with a substantial global warming potential. The CH4 catalytic combustion offers an efficient method for the elimination of CH4. However, improving the catalytic performance of Pd-based materials for low-temperature CH4 combustion remains a big challenge. In this study, we synthesized an enhanced Pd/5NiAlOx catalyst that demonstrated superior catalytic activity and improved water resistance compared to the Pd/Al2O3 catalyst. Specifically, the T90 was decreased by over 100 °C under both dry and wet conditions. Introducing Ni resulted in an enormously enhanced number of oxygen defects on the obtained 5NiAlOx support. This defect-rich support facilitates the anchoring of PdO through increased electron transfer, thereby inhibiting the production of high-valence Pd(2+δ)+ and stimulating the generation of unsaturated Pd sites. Pd0 can effectively activate surface oxygen and PdO plays a significant role in activating CH4, resulting in high activity for Pd/5NiAlOx. On the other hand, the increased water resistance of Pd/5NiAlOx was mainly due to the generation of *OOH species and the lower accumulation of surface -OH species during the reaction process.
BACKGROUND & AIMS: The AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical trials, and an additional 13 folate trials have been published since then. This meta-analysis aims to fill in critical evidence gaps by comprehensively evaluating 21 published trials with particular attention given to identifying the true influences through stratification. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 4, 2023. This study included all randomized controlled trials (RCTs) of folic acid with stroke as one of the reporting endpoints. Relative risks and 95% confidence intervals were used to assess the association between folic acid supplementation and the risk of stroke in a random-effects model. RESULTS: Results from the 21 pooled RCTs totaling 115,559 participants showed that folic acid supplementation significantly reduced the risk of stroke by 10% (RR 0.90, 95%CI 0.83 to 0.98). Subgroup analyses showed that folic acid efficacy was greater in areas without fortified grain or with partially-fortified grain (RR = 0.83, 95% CI 0.75 to 0.93; RR = 1.04 in areas with grain fortification, P-interaction = 0.003). In this group, folic acid supplementation was most efficacious in those without a history of stroke or myocardial infarction (RR = 0.77, 95% CI 0.68 to 0.86; RR = 0.94 for participants with a history of stroke or myocardial infarction, P-interaction = 0.008). The efficacy of folic acid remained consistent regardless of baseline folate levels, folic acid dosage, baseline vitamin B12 levels, vitamin B12 dosage, homocysteine reduction, intervention duration, and whether folic acid was taken alone or in combination (all P-interaction>0.05). All 21 trials were free of attrition bias and reporting bias, and there was no significant publication bias. CONCLUSIONS: This is by far the largest meta-analysis of RCTs regarding folic acid supplementation and stroke, demonstrating the overall benefit of folic acid for stroke prevention. Grain fortification and history of stroke or myocardial infarction may be the most important influences on the efficacy of folic acid for stroke prevention.
Cardiovascular diseases are significant contributors to human mortality, closely associated with inflammation. With the changing living conditions and the extension of human lifespan, greater attention has been directed towards understanding the impact of early, long-term events on the development of cardiovascular events. Lifestyle factors such as stress, unhealthy diet and physical inactivity can increase the risk of cardiovascular diseases. Interestingly, even if the risk factors are addressed later, their influence may persist. Recently, the concept of trained innate immunity (TRIM), defined as sustained alterations in the function of innate immunocyte that promote a more robust response to downstream stimuli, has been proposed to be involved in cardiovascular diseases. It is hypothesized that TRIM may serve as a mediator bridging the impacts of aforementioned risk factors. This review aims to elucidate the role of TRIM in cardiovascular diseases and highlight its significance in uncovering new mechanisms and therapeutic targets.
Emission models of volatile organic compounds (VOCs) from individual indoor building materials have been developed and validated. However, multiple indoor building materials release VOCs simultaneously, and neither single building material nor multiple building material emission models can predict the entire release cycle of VOCs accurately. This study established a long- and short-term numerical prediction model for indoor VOC concentration. The model includes an attenuation coefficient θ. To describe the decay rate of the total VOC content, which is mainly influenced by time, and by designing experiments and testing in environmental warehouses under different seasonal conditions, the value of θ was first obtained. Then, after successfully plotting the emission curve of indoor pollutant concentration over time through numerical solution and using θ, the VOC content was corrected for various seasonal conditions. On the basis of this model, an exposure dose integration algorithm was proposed to evaluate the environmental health risks, as an application of this model. In comparison with previous research results and experimental data, this model has better predictive performance.
BACKGROUND: Studies on the relationship between the preoperative quantitative flow ratio (QFR) and parameters of intraoperative transit time flow measurement (TTFM) are extremely rare. In addition, the predictive value of QFR and TTFM parameters for early internal mammary artery (IMA) failure after coronary artery bypass grafting still needs to be validated.MethodsâandâResults: We retrospectively collected data from 510 patients who underwent in situ IMA grafting to the left anterior descending (LAD) artery at Fuwai Hospital. Spearman correlation coefficients between preoperative QFR of the LAD artery and intraoperative TTFM parameters of the IMA were -0.13 (P=0.004) for mean graft flow (Qm) and 0.14 (P=0.002) for the pulsatility index (PI). QFR and TTFM exhibited similar and good predictive value for early IMA failure (5.7% at 1 year), and they were better than percentage diameter stenosis (area under the curve 0.749 for QFR, 0.733 for Qm, 0.688 for PI, and 0.524 for percentage diameter stenosis). The optimal cut-off value of QFR was 0.765. Both univariate and multivariable regression analyses revealed that QFR >0.765, Qm ≤15 mL/min, and PI >3.0 independently contributed to early IMA failure. CONCLUSIONS: There were statistically significant correlations between preoperative QFR of the LAD artery and intraoperative TTFM parameters (Qm, PI) of the IMA. Preoperative QFR and intraoperative Qm and PI exhibited excellent predictive value for early IMA failure.
Advancements in anticancer strategies spotlight proteolysis targeting chimera (PROTAC) technology, yet it is hindered by poor water solubility and bioavailability. This study introduces a novel amphiphilic PROTAC, B1-PEG, synthesized through PEGylation of an optimized PROTAC molecule, B1, to enhance its properties. B1-PEG is engineered to self-organize into micelles in water and releases its active form in response to the tumor-specific high GSH environment. Comparative pharmacokinetic analysis revealed B1-PEG's superior bioavailability at 84.8%, outperforming the unmodified PROTAC molecule B1. When tested in a H3122 xenograft mouse model, B1-PEG significantly regressed tumors, underscoring its potential as a formidable candidate in targeted cancer therapy. Our findings offer a promising direction for overcoming bioavailability limitations in PROTAC drug design.
Carotid atherosclerosis is a major cause of stroke. Hemodynamic forces, such as shear stress and oscillatory shear, play an important role in the initiation and progression of atherosclerosis. The alteration of the immune microenvironment is the fundamental pathological mechanism by which diverse external environmental factors impact the formation and progression of plaques. However, Current research on the relationship between hemodynamics and immunity in atherosclerosis still lack of comprehensive understanding. In this study, we combined computational fluid dynamics (CFD) and Mass cytometry (CyTOF) technologies to explore the changes in the immune microenvironment within plaques under different hemodynamic conditions. Our results indicated that neutrophils were enriched in adverse flow environments. M2-like CD163+CD86+ macrophages were predominantly enriched in high WSS and low OSI environments, while CD163-CD14+ macrophages were enriched in low WSS and high OSI environments. Functional analysis further revealed T cell pro-inflammatory activation and dysregulation in modulation, along with an imbalance in M1-like/M2-like macrophages, suggesting their potential involvement in the progression of atherosclerotic lesions mediated by adverse flow patterns. Our study elucidated the potential mechanisms by which hemodynamics regulated the immune microenvironment within plaques, providing intervention targets for future precision therapies.
The cast thin sections of tight oil reservoirs contain important parameters such as rock mineral composition and content, porosity, permeability and stratigraphic characteristics, which are of great significance for reservoir evaluation. The use of deep learning technology for intelligent identification of thin section images is a development trend of mineral identification. However, the difficulty of making cast thin sections, the complexity of the making process and the high cost of thin section annotation have led to a lack of cast thin section images, which cannot meet the training requirements of deep learning image recognition models. In order to increase the sample size and improve the training effect of deep learning model, we proposed a generation and annotation method of thin section images of tight oil reservoir based on deep learning, by taking Fuyu reservoir in Sanzhao Sag as the target area. Firstly, the Augmentor strategy space was used to preliminarily augment the original images while preserving the original image features to meet the requirements of the model. Secondly, the category attention mechanism was added to the original StyleGAN network to avoid the influence of the uneven number of components in thin sections on the quality of the generated images. Then, the SALM annotation module was designed to achieve semi-automatic annotation of the generated images. Finally, experiments on image sharpness, distortion, standard accuracy and annotation efficiency were designed to verify the advantages of the method in image quality and annotation efficiency.
For the last two decades, the aromatic aldehyde 5-hydroxymethyl-furfural (5-HMF) has been the subject of several investigations for its pharmacologic potential. In 2004, the Safo group reported that 5-HMF has potent antisickling activity by targeting and ameliorating the primary pathophysiology of hypoxia-induced sickling of erythrocytes (red blood cells [RBC]). Following the encouraging outcome of the preclinical and phase I/II clinical studies of 5-HMF for the treatment of sickle cell disease (SCD), there have been multiple studies suggesting 5-HMF has several other biological or pharmacologic activities, including anti-allergic, antioxidant, anti-hypoxic, anti-ischemic, cognitive improvement, anti-tyrosinase, anti-proliferation, cytoprotective, and anti-inflammatory activities. The wide range of its effects makes 5-HMF a potential candidate for treating a variety of diseases including cognitive disorders, gout, allergic disorders, anemia, hypoxia, cancers, ischemia, hemorrhagic shock, liver fibrosis, and oxidative injury. Several of these therapeutic claims are currently under investigation and, while promising, vary in terms of the strength of their evidence. This review presents the research regarding the therapeutic potential of 5-HMF in addition to its sources, physicochemical properties, safety, absorption, distribution, metabolism, and excretion (ADME) profiles.
We describe a simple and robust oxidation strategy for preparing N-terminal thiazolidine-containing peptide thioesters from peptide hydrazides. We find for the first time that l-thioproline can be used as a protective agent to prevent the nitrosation of N-terminal thiazolidine during peptide hydrazide oxidation. The thioproline-based oxidation strategy has been successfully applied to the chemical synthesis of CC chemokine ligand-2 (69aa) and omniligase-C (113aa), thereby demonstrating its utility in hydrazide-based native chemical ligation.
Electrochemical sensors play a crucial role in the detection of different analytes in complex matrices, and their performance is highly dependent on the electrode capacity. However, most of the available electrodes can only be used for single-component detection, so it is urgent to develop electrodes with high sensitivity and selectivity for different components. Herein, we report an amphiprotic amino-bonded carbon nanotube-Ag/Cu/Al nanoparticle/polystyrene-coated paper electrode (CNT-Ag-Cu-Al/PS electrode), which can be used for the measurement of glucose (Glc), oxytetracycline (OTC), and hydroquinone (HQ), respectively. The results showed that the analytical sensitivity and selectivity of the CNT-Ag-Cu-Al/PS electrode were comparable to those of single metal-coated paper substrate. The developed electrode also exhibited excellent linear responses for Glc, OTC, and HQ in the ranges of 1.0-1000.0 µM, 1.0 × 10-2 to 10.0 µM, and 5.0 × 10-3 to 50.0 µM, and the limits of detection (LODs) were 0.2055 µM (Glc), 0.0074 µM (OTC), and 0.0048 µM (HQ). Owing to the characteristics of good selectivity, anti-interference, stability, and reproducibility, the CNT-Ag-Cu-Al/PS paper electrode has been successfully applied to the detection of these analytes in complex human body fluids, food, and environmental waters. The paper electrode is promising for the detection of target compounds in complex matrices.
The TOR1B gene is known to play a pivotal role in maintaining cellular homeostasis and responding to endoplasmic reticulum stress. However, its involvement in cancer remains relatively understudied. This study seeks to explore the prognostic implications of TOR1B across various cancers, with a specific focus on Basal-like Breast Cancer (BLBC) and its underlying cellular mechanisms. Through comprehensive analysis of data from TCGA, TARGET, GEO, and GTEx, we investigated TOR1B expression and its correlation with patient outcomes. Furthermore, in vitro experiments conducted on BLBC cell lines examined the impact of TOR1B modulation on cell viability, apoptosis, and metabolic activity under varying oxygen levels. Our statistical analysis encompassed differential expression analysis, survival analysis, and multivariate Cox regression. Our findings indicate that TOR1B is overexpressed in BLBC and other cancers, consistently correlating with poorer prognosis. Elevated TOR1B levels were significantly associated with reduced overall and disease-free survival in BLBC patients. In vitro experiments further revealed that TOR1B knockdown augmented apoptosis and influenced metabolic activity, particularly under hypoxic conditions, highlighting its potential role in cancer cell adaptation to stress. Overall, our study underscores the importance of TOR1B in cancer progression, particularly in BLBC, where it serves as a notable prognostic indicator. The interaction between TOR1B and metabolic pathways, as well as its regulation by HIF-1α, suggests its significance in adapting to hypoxia, thereby positioning TOR1B as a promising therapeutic target for aggressive breast cancer subtypes.
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Prognosis , Cell Line, Tumor , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Apoptosis
Polyoxometalates (POMs) have drawn significant attention on account of their structural designability, compositional diversity and great potential applications. As an indispensable branch of POMs, selenotungstates (SeTs) have been synthesized extensively. Some SeTs have been applied as sensing materials for detecting biomarkers (e.g., metabolites, hormones, cancer markers). To gain a comprehensive understanding of advancements in SeT-based sensing materials, we present an overview that encapsulates the sensing performances and mechanisms of SeT-based biosensors. SeT-based biosensors are categorized into electrochemical catalytic biosensors, electrochemical affinity biosensors, "turn-off" fluorescence biosensors and "turn-on" fluorescence biosensors. We anticipate the expansive potential of SeT-based biosensors in wearable and implantable sensing technologies, which promises to catalyze significant breakthroughs in SeT-based biosensors.
Introduction: The burden of colorectal cancer (CRC) plays a pivotal role in the global cancer epidemic. Our study reported the incidence trends in CRC and the associated effects of age, period, and birth cohort in 204 countries and territories over the past 30 years. Methods: The incidence data of CRC were extracted from the Global Burden of Disease Study (GBD) 2019. We performed the age-period-cohort (APC) model to estimate the overall annual percentage change (net drift) in the incidence rate, the annual percentage change by age group (local drift), and the relative risk (period and cohort effects) of the period and cohort in CRC during 1990-2019. This approach allows examining and distinguishing age, period, and cohort effects in incidence and potentially distinguishing colorectal cancer gaps in prevention and screening. Results: In 2019, the incidence of CRC was 2.17 (95% UI 2.00-2.34) million, of which China, the United States of America, and Japan had the highest incidence population, accounting for 45.9% of the global population. The age-standardized incidence rate (ASIR) was 26.7 (95% UI 28.9-24.6) per 100,000 people, of which 30 countries had an incidence rate greater than 40.0 per 100,000 people. From 1990 to 2019, the middle SDI region had the largest increase in incidence rate, with a net drift of 2.33% (95% CI 2.2-2.46%, p < 0.001). Globally, the incidence population was concentrated in the age group of 50-69 years, and the age group of 30-34 years had the largest increase in incidence rate (local drift 1.19% (95% CI 1.01-1.37%)). At the same time, the sex and age distributions of CRC incidence had significant heterogeneity across regions and countries. In the past 30 years, the incidence rate in 31 countries has been well controlled (net drift <0), and most of them were concentrated in high-and high-middle-SDI regions, such as Australia, Czechia, and Belgium, and the relative risk of incidence generally improved over time and consecutive young birth cohorts. CRC incidence showed an unfavorable trend (net drift ≥1%) in 89 countries, of which 27 countries were more significant (net drift >2%), mostly concentrated in the middle SDI region, such as China, Mexico, and Brazil, and the risk of period and birth cohort was unfavorable. Conclusion: Globally, the incidence of CRC has shown an overall upward trend over the past 30 years, with the exception of some countries with higher SDI values. Significant age-period-cohort differences were observed in the risk of incidence in CRC worldwide. Effective prevention and control policies need to take into account the age-period-cohort effect characteristics of different regions.
Colorectal Neoplasms , Global Burden of Disease , Humans , Colorectal Neoplasms/epidemiology , Incidence , Middle Aged , Male , Aged , Female , Adult , Cohort Studies , Global Health/statistics & numerical data , Aged, 80 and over , Age Factors , Young Adult
Background: X-linked hypophosphatemia (XLH, OMIM 307800) is a rare phosphorus metabolism disorder caused by PHEX gene variants. Many variants simply classified as missense or nonsense variants were only analyzed at the DNA level. However, growing evidence indicates that some of these variants may alter pre-mRNA splicing, causing diseases. Therefore, this study aimed to use bioinformatics tools and a minigene assay to ascertain the effects of PHEX variations on pre-mRNA splicing. Methods: We analyzed 174 variants in the PHEX gene described as missense or nonsense variants. Finally, we selected eight candidate variants using bioinformatics tools to evaluate their effects on pre-mRNA splicing using a minigene assay system. The complementary DNA (cDNA) sequence for the PHEX gene (RefSeq NM_000444.6) serves as the basis for DNA variant numbering. Results: Of the eight candidate variants, three were found to cause abnormal splicing. Variants c.617T>G p.(Leu206Trp) and c.621T>A p.(Tyr207*) in exon 5 altered the splicing of pre-mRNA, owing to the activation of a cryptic splice site in exon 5, which produced an aberrant transcript lacking a part of exon 5, whereas variant c.1700G>C p.(Arg567Pro) in exon 16 led to the activation of a cryptic splice site in intron 16, resulting in a partial inclusion of intron 16. Conclusion: Our study employed a minigene system, which has a great degree of flexibility to assess abnormal splicing patterns under the circumstances of patient mRNA samples that are not available, to explore the impact of the exonic variants on pre-mRNA splicing. Based on the aforementioned experimental findings, we demonstrated the importance of analyzing exonic variants at the mRNA level.
Background: Complex degenerative cervical spondylotic myelopathy (DCM) is characterized by a variety of complex imaging features. The surgical method for DCM remains controversial. This study aimed to examine the correlation between the imaging characteristics of DCM with varying degrees of complexity and the surgical approach and clinical outcome. Methods: A retrospective cohort study involving retrospective data collection was performed. A total of 139 patients with DCM who underwent surgery between January 2015 and January 2018 in the Orthopedics Department of Shanxi Bethune Hospital were divided into 3 groups according to the complexity of imaging features: 18 patients in the mild group, 66 patients in the moderate group, and 55 patients in the severe group. The Visual Analog Scale (VAS) and Japanese Orthopaedic Association (JOA) scores were used to compare the effects of neck pain and neural function prior to surgery according to the rate of improvement as of the last follow-up. Routine X-ray films were obtained at the follow-up of 3-6 months. The necessity of computed tomography (CT) and magnetic resonance imaging (MRI) examinations was determined based on clinical findings and X-ray images. Analysis of variance (ANOVA) was used to compare groups, the least significant difference (LSD) test was used for multiple comparisons, and the Chi-square test was used to compare classification indicators (imaging manifestations, gender), with P<0.05 being statistically significant. Binary logistic regression analysis was performed to determine the primary influencing factors of the JOA recovery rate. Results: In all three groups, JOA and VAS scores at the final follow-up were significantly higher than those before surgery (P<0.001). There were significant differences in the preoperative VAS and JOA scores between any two groups, as well as in the VAS and JOA scores and improvement rates at the last follow-up between the mild group and the moderate group and between the mild group and the severe group (P<0.001). Age, preoperative JOA scores, MRI intramedullary hyperintensity signal, and the degree of spinal cord compression were primarily related to the nervous system recovery rate (P<0.001). Conclusions: Age, MRI intramedullary hyperintensity signal, degree of spinal cord compression, and other variables were associated with the improvement of neural function in patients with DCM. Therefore, in addition to the JOA improvement rate or VAS score, additional factors, such as the patient's condition, the improvement in quality of life, and the patient's financial capacity, should be considered in evaluating the improvement of postoperative neck pain and neural function.
Introduction: This study examines the seasonal and genetic characteristics of human metapneumovirus (HMPV) in Henan from 2017 to 2023. Methods: Samples from patients with acute respiratory infection (ARI) testing positive for HMPV were subjected to real-time reverse transcription polymerase chain reaction The G gene was amplified and sequenced from these samples for epidemiological and phylogenetic analysis. Results: We enrolled 2,707 ARI patients from October 2017 to March 2023, finding an HMPV positivity rate of 6.17% (167/2,707). Children under five exhibited the highest infection rate at 7.78% (138/1,774). The 2018 and 2019 HMPV outbreaks predominantly occurred in spring (March to May), with peak positivity rates of 31.11% in May 2018 and 19.57% in May 2019. A notable increase occurred in November 2020, when positivity reached a historic high of 42.11%, continuing until January 2021. From February 2021 through March 2023, no significant seasonal peaks were observed, with rates ranging from 0% to 8.70%. Out of 81 G gene sequences analyzed, 46.91% (38/81) were identified as subtype A (A2c: 45.67%, 37/81; A2b: 1.23%, 1/81) and 53.09% (43/81) as subtype B (B1: 9.88%, 8/81; B2: 43.21%, 35/81). Notably, an AAABBA switch pattern was observed in HMPV subtypes. The dominant strains were A2c111nt-dup in subtype A and B2 in subtype B. Conclusions: Six years of surveillance in Henan Province has detailed the seasonal and genetic dynamics of HMPV, contributing valuable insights for the control and prevention of HMPV infections in China. These findings support the development of targeted HMPV vaccines and immunization strategies.
P-element-induced wimpy testis-interacting RNAs (piRNAs), a class of small noncoding RNAs with about 24-32 nucleotides, often interact with PIWI proteins to form a piRNA/PIWI complex that could influence spermiogenesis, transposon silencing, epigenetic regulation, etc. PIWI proteins have a highly conserved function in a variety of species and are usually expressed in germ cells. However, increasing evidence has revealed the important role of the piRNA/PIWI complex in the occurrence and prognosis of various human diseases and suggests its potential application in the diagnosis and treatment of related diseases, becoming a prominent marker for these human diseases. Recent studies have confirmed that piRNA/PIWI complexes or piRNAs are abnormally expressed in some viral infections, effecting disease progression and viral replication. In this study, we reviewed the association between the piRNA/PIWI complex and several human disease-associated viruses, including human papillomavirus, human immunodeficiency virus, human rhinovirus, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, and herpes simplex virus type 1.
