Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage.

Cholesterol is an important component of plasma membranes and participates in many basic life functions, such as the maintenance of cell membrane stability, the synthesis of steroid hormones, and myelination. Cholesterol plays a key role in the establishment and maintenance of the central nervous system. The brain contains 20% of the whole body's cholesterol, 80% of which is located within myelin. A huge number of processes (e.g., the sterol regulatory element-binding protein pathway and liver X receptor pathway) participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis, intracellular transport, and efflux. Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences. Therefore, we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases. Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype, with high mortality and morbidity. Historical cholesterol levels are associated with the risk of intracerebral hemorrhage. Moreover, secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation, such as neuroinflammation, demyelination, and multiple types of programmed cell death. Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage. In this paper, we review normal cholesterol metabolism in the central nervous system, the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage, and the links between cholesterol metabolism and cell death. We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

Narcissism, perfectionism, and self-promoting behavior on social networking sites among university students in Pakistan / Narcisismo, perfeccionismo y comportamiento de autopromoción en sitios de redes sociales entre estudiantes universitarios en Pakistán

Existe un debate considerable en la literatura sobre cómo el narcisismo predice diversos comportamientos asociados con la utilidad de los sitios de redes sociales, pero los investigadores han prestado menos atención a explorar los mediadores potenciales de esta relación. Con base en la literatura existente, anticipamos que el narcisismo predice comportamientos de autopromoción en los sitios de redes sociales. El estudio actual también investigó el papel mediador del perfeccionismo multidimensional entre el narcisismo y el comportamiento de autopromoción. Se recopiló un total de 605 cuestionarios completos de estudiantes de universidades de Rawalpindi e Islamabad, Pakistán, mediante un muestreo conveniente. El estudio utilizó el Inventario de Personalidad Narcisista (Ames et al., 2006), un cuestionario de desarrollo propio sobre comportamiento de autopromoción en sitios de redes sociales y la Escala de Perfeccionismo Multidimensional (Hewitt et al., 1991). Los hallazgos indicaron que las mujeres en comparación con los hombres y las solteras en comparación con las casadas obtuvieron puntuaciones más altas en narcisismo. Los niveles educativos más altos se asociaron con tasas más altas de narcisismo. Los resultados también sugieren que el narcisismo se correlaciona con el perfeccionismo orientado a uno mismo y, más significativamente, con el narcisismo orientado a los demás. El perfeccionismo orientado a uno mismo y a los demás medió significativamente la relación entre el narcisismo y el comportamiento de autopromoción en los sitios de redes sociales.(AU)

There is considerable debate in the literature about how narcis-sism predicts various behaviors associated with the utility of social net-working sites, but researchers have paid less attention to exploring the po-tential mediators of this relationship.Based on the existing literature, we anticipated that narcissism predicts self-promoting behaviors on social networking sites. The current study also investigated the mediating role of multidimensional perfectionismbetween narcissism and self-promoting behavior. A total of 605 complete questionnaires weregathered fromstu-dents from universities from Rawalpindi and Islamabad, Pakistan using convenient sampling. The study used Narcissistic Personality Inventory (Ames et al., 2006), self-developed Self-promoting Behavior on social net-working sites questionnaire, and the Multidimensional Perfectionism Scale (Hewitt et al., 1991). Findings indicated that females as compared to males and single as comparedto married individuals scored higher on narcissism. Higher educational levels were associated with higher rates of narcissism. The results also suggestthat narcissism correlated with self-oriented per-fectionism, and more significantlywith others-oriented narcissism. Self-oriented and others-oriented perfectionism significantly mediated the rela-tionship between narcissism and self-promoting behavior on social net-working sites.(AU)

A cargo sorting receptor mediates chloroplast protein trafficking through the secretory pathway.

Nucleus-encoded chloroplast proteins can be transported via the secretory pathway. The molecular mechanisms underlying the trafficking of chloroplast proteins between the intracellular compartments are largely unclear, and a cargo sorting receptor has not previously been identified in the secretory pathway. Here we report a cargo sorting receptor that is specifically present in Viridiplantae and mediates the transport of cargo proteins to the chloroplast. Using a forward genetic analysis, we identified a gene encoding a transmembrane protein (MtTP930) in barrel medic (Medicago truncatula). Mutation of MtTP930 resulted in impaired chloroplast function and a dwarf phenotype. MtTP930 is highly expressed in the aerial parts of the plant and is localized to the ER exit sites (ERESs) and Golgi. MtTP930 contains typical cargo sorting receptor motifs, interacts with Sar1, Sec12 and Sec24, and participates in coat protein II (COPII) vesicular transport. Importantly, MtTP930 can recognize the cargo proteins plastidial N-glycosylated nucleotide pyrophosphatase/ phosphodiesterase (MtNPP) and α-carbonic anhydrase (MtCAH) in the ER, and then transport them to the chloroplast via the secretory pathway. Mutation of a homolog of MtTP930 in Arabidopsis (Arabidopsis thaliana) resulted in a similar dwarf phenotype. Furthermore, MtNPP-GFP failed to localize to chloroplasts when transgenically expressed in Attp930 protoplasts, implying that these cargo sorting receptors are conserved in plants. These findings fill a gap in our understanding of the mechanism by which chloroplast proteins are sorted and transported via the secretory pathway.

Unpacking the hazards: An analytic study of injury patterns and risk factors in urban instant delivery.

The rapid growth of urban instant delivery, facilitated by digital platforms and characterized by on-demand, short-term, task-based labor, has raised concerns about safety, particularly with the increasing frequency of instant delivery crashes (IDCs). This study addresses knowledge gaps in understanding injury patterns and risk factors associated with IDCs. Utilizing data extracted from judicial verdicts on IDC disputes in China, encompassing demographic, contextual, crash, and injury information, the research employs ordered logit regression to identify significant factors affecting injury patterns, the number of injuries per person (IPP), and injury severity. Overall, traffic injuries related to instant delivery services have gradually improved since 2020, as evidenced by the severity of individual accidents, the number of injuries, and the economic losses. Analysis of 648 injuries among 448 non-fatal victims reveals a prevalence of lower extremity injuries, followed by external, upper extremity, and head injuries. While the majority of victims suffered a single injury, approximately 22 % experienced major injuries. Female delivery riders exhibited higher injury ratios across various body regions. Rider risk behavior, type of delivery vehicles, and the mode of transport of non-delivery travelers emerged as significant influencers of injury patterns. Notably, functional and physical intersection areas exhibited the highest injury ratios among facility types. Contrary to conventional wisdom, older riders and travelers aged above 50 were associated with higher injury severity, challenging the perception of young age as the primary risk factor. The prominence of lower extremity injuries underscores the necessity for heightened protective measures for delivery riders. Major injuries among victims emphasize potential long-term consequences and associated costs. The significance of gender, age, and risk behavior as determining factors highlights the need for targeted safety interventions. These findings offer crucial insights for stakeholders, guiding the formulation of precise safety measures and informed policy initiatives within the dynamic landscape of instant delivery safety.

Development and Validation of Machine Learning-Based Models for Prediction of Intensive Care Unit Admission and In-Hospital Mortality in Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Background: This present work focused on predicting prognostic outcome of inpatients developing acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and enhancing patient monitoring and treatment by using objective clinical indicators. Methods: The present retrospective study enrolled 322 AECOPD patients. Registry data downloaded based on COPD Pay-for-Performance Program database from January 2012 to December 2018 were used to check whether the enrolled patients were eligible. Our primary and secondary outcomes were ICU admission and in-hospital mortality, respectively. The best feature subset was chosen by recursive feature elimination. Moreover, seven machine learning (ML) models were trained for forecasting ICU admission among AECOPD patients, and the model with the most excellent performance was used. Results: According to our findings, random forest (RF) model showed superb discrimination performance, and the values of area under curve (AUC) were 0.973 and 0.828 in training and test cohorts, separately. Additionally, according to decision curve analysis, the net benefit of RF model was higher when differentiating patients with a high risk of ICU admission at a <0.55 threshold probability. Moreover, the ML-based prediction model was also constructed to predict in-hospital mortality, and it showed excellent calibration and discrimination capacities. Conclusion: The ML model was highly accurate in assessing the ICU admission and in-hospital mortality risk for AECOPD cases. Maintenance of model interpretability helped effectively provide accurate and lucid risk prediction of different individuals.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

Effects of recreational team sports on the metabolic health, body composition and physical fitness parameters of overweight and obese populations: A systematic review.

This systematic review aims to provide a summary of the results from individual studies that specifically focused on overweight or obese populations, regardless of age or sex. The goal is to determine the effects of structured recreational team sports interventions (TSG) on metabolic health, body composition and physical fitness parameters when compared to passive or active control groups. This study adhered to the PRISMA guidelines for reporting a systematic review. A thorough examination of relevant literature was conducted on November 06, 2023, using three prominent databases: PubMed, Scopus, and the Web of Science. Inclusion criteria considered overweight (e.g., BMI 25.0-29.9 kg/m2) and obese (e.g., BMI > 30 kg/m2) populations exposed to training interventions using recreational team sports, while the comparator group consisted of the same populations not exposed to exercise (passive controls) or exposed to alternative training methods. The primary outcomes of interest were metabolic health parameters (glucose, waist circumference, blood pressure, cholesterol, triglycerides), body composition (e.g., fat mass, lean mass), as well as physical fitness parameters (e.g., aerobic fitness, muscular fitness). Only studies with two- or multi-arm designs, whether randomized or not, were eligible for inclusion. The PEDro scale was used to assess the methodological bias of the included studies. Out of the initial 275 titles retrieved, we deemed ten eligible for our study. In terms of body composition, TSG demonstrated a significant decrease in body mass index across three studies (-2.3 to -5.1%) and a significant reduction in waist circumference in four studies (-4.6% to -8.4%). Regarding blood pressure, TSG exhibited a significant decrease in systolic blood pressure in two studies (-3.9% to -8.3%), while diastolic blood pressure showed a significant decrease in only one study (-7.3%). Cholesterol levels saw a significant decrease in TSG in three studies (-7.0% to -9.7%), and triglyceride levels showed a significant reduction in four studies (-16.4% to -20.1%). In terms of aerobic fitness, TSG demonstrated within-group improvements in the field-based tests in three studies (8.1% to 79.0%), and within-group improvements in maximal oxygen uptake in four studies (6.5% to 31.0%), with significant favoring of TSG in most studies. Overall, TSG demonstrated significant benefits for overweight and obese populations compared to the control group, particularly in terms of improvements in body mass index, systolic blood pressures, cholesterol and triglyceride levels, and aerobic fitness. Future research ought to concentrate on tailoring responses to varying training volumes on an individualized basis.

Differential expression profiles and functional prediction of circular RNAs in lung cancer patients with chronic obstructive pulmonary disease: a pilot study.

Chronic obstructive pulmonary disease (COPD), characterized by clinical sub-phenotypes such as emphysema (E) and chronic bronchitis (CB), is associated with a greater risk of lung cancer (LC). This study aimed to assess the expression patterns of circRNA and their potential functional involvement in LC patients with COPD. A circRNA microarray was used to characterize differentially expressed circRNAs (DEcircRNAs) profiles. A total of 176, 240, 163, and 243 DEcircRNAs were identified in comparisons between CB vs. LC patients (Con), E vs. Con, E vs. CB, and CBE vs. Con, respectively. DEcircRNAs in all comparison groups were primarily associated with immune-related GO terms and were also enriched in immune and inflammatory pathways. In total, 49 DEcircRNAs were significantly correlated with the infiltration of multiple immune cells. Among them, hsa-MROH9_0001 and hsa-RP11-35J10_0013 were positively and negatively correlated with plasma cells and T-cell CD4 memory resting cells, respectively; these two DEcircRNA-sponged miRNAs have good diagnostic performance. WGCNA identified six key circRNAs associated with CB progression. The expression patterns of hsa-MROH9_0001 and circRNA_21729 in E and CB groups were confirmed by RT-qPCR. In conclusion, we reported circRNA profiles and the findings demonstrated that hsa-MROH9_0001 and circRNA_21729 may be potential therapeutic targets for LC with COPD.

Trace Iron-Doped Nickel-Cobalt selenide with rich heterointerfaces for efficient overall water splitting at high current densities.

Developing bifunctional electrocatalysts based on non-precious metals for overall water splitting, while maintaining high catalytic activity and stability under high current densities, remains challenging. Herein, we successfully constructred trace iron-doped nickel-cobalt selenide with abundant CoSe2 (210)-Ni3Se4 (202) heterointerfaces via a simple one-step selenization reaction. The synthesized Fe-NiCoSex/NCFF (NCFF stands for nickel-cobalt-iron foam) exhibits outstanding hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) activity with low overpotentials of 328 mV for HER and 345 mV for OER at a high current density of 1000 mA cm-2, while maintaining stability for over 20 h. Additionally, the Fe-NiCoSex/NCFF exhibits the lowest Tafel slope values for both HER (33.7 mV dec-1) and OER (55.92 mV dec-1), indicating the fastest kinetics on its surface. The Fe-NiCoSex/NCFF features uniformly distributed micrometer-sized selenide particles with dense nanowires on their surface, providing a large reactive surface area and abundant active sites. Moreover, X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) analyses reveal that the catalyst is composed of nickel, cobalt, and iron, forming micrometer-sized particles with both crystalline and amorphous phases, thereby enhancing HER and OER performance under high current density. Density functional theory (DFT) calculations demonstrate that the heterostructure CoSe2 (210)-Ni3Se4 (202), with high electron density and suitable adsorption capacity for reaction intermediates, and low energy barriers for HER (-0.384 eV) and OER (ΔG1st: 0.243 eV, ΔG2nd: 0.376 eV), serves as an active center for both HER and OER.

Stabilization of TGF-ß Receptor 1 by a Receptor-Associated Adaptor Dictates Feedback Activation of the TGF-ß Signaling Pathway to Maintain Liver Cancer Stemness and Drug Resistance.

Dysregulation of the transforming growth factor-ß (TGF-ß) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug-resistant CSCs. Through a genome-wide CRISPR activation screen utilizing stem-like drug-resistant properties as a readout, the TGF-ß receptor-associated binding protein 1 (TGFBRAP1) is identified as a TGF-ß-inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF-ß receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF-ß signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly-ubiquitination and proteasomal degradation. Moreover, hyperactive TGF-ß signaling in turn up-regulates TGFBRAP1 expression in drug-resistant CSC-like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF-ß signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF-ß signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1-mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF-ß signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.

Internal Superwettability Inversion of a COF-Encapsulated Melamine Sponge Prepared by a One-Step Synthesis at Room Temperature.

Superwettable materials have been attracting attention due to their unique properties, showing great application prospects in a variety of fields including oil-water separation. Herein, a kind of covalent organic framework (COF)-encapsulated melamine sponge (MS) capable of internal superwettability inversion is prepared by a one-step synthesis at room temperature. COF is produced in situ on the skeleton of MS, which is favorable for practical application, and the prepared COF-encapsulated sponge (MS@COF) exhibits superhydrophobicity (water contact angle of about 157.0°) due to the rough surface provided by the micro/nanostructure of COF. More importantly, MS@COF displays reversibly superhydrophilicity by simple prewetting, achieving superwettability inversion conveniently, unlike the previous switchable materials that rely on external conditions. This facile intrinsic superwettability inversion greatly enriches the application prospects of this kind of smart sponge.

Optimal dosage ranges of various exercise types for enhancing timed up and go performance in Parkinson's disease patients: a systematic review and Bayesian network meta-analysis.

Objective: To examine the dose-response relationship between specific types of exercise for alleviating Timed up and Go (TUG) in Parkinson's disease PD. Design: Systematic review and Bayesian network meta-analysis. Data sources: PubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 5th, 2024. Study analysis: Data analysis was conducted using R software with the MBNMA package. Effect sizes of outcome indicators were expressed as mean deviation (MD) and 95% confidence intervals (95% CrI). The risk of bias in the network was evaluated independently by two reviewers using ROB2. Results: A total of 73 studies involving 3,354 PD patients. The text discusses dose-response relationships in improving TUG performance among PD patients across various exercise types. Notably, Aquatic (AQE), Mix Exercise (Mul_C), Sensory Exercise (SE), and Resistance Training (RT) demonstrate effective dose ranges, with AQE optimal at 1500 METs-min/week (MD: -8.359, 95% CI: -1.398 to -2.648), Mul_C at 1000 METs-min/week (MD: -4.551, 95% CI: -8.083 to -0.946), SE at 1200 METs-min/week (MD: -5.145, 95% CI: -9.643 to -0.472), and RT at 610 METs-min/week (MD: -2.187, 95% CI: -3.161 to -1.278), respectively. However, no effective doses are found for Aerobic Exercise (AE), Balance Gait Training (BGT), Dance, and Treadmill Training (TT). Mind-body exercise (MBE) shows promise with an effective range of 130 to 750 METs-min/week and an optimal dose of 750 METs-min/week (MD: -2.822, 95% CI: -4.604 to -0.996). According to the GRADE system, the included studies' overall quality of the evidence was identified moderate level. Conclusion: This study identifies specific exercise modalities and dosages that significantly enhance TUG performance in PD patients. AQE emerges as the most effective modality, with an optimal dosage of 1,500 METs-min/week. MBE shows significant benefits at lower dosages, catering to patients with varying exercise capacities. RT exhibits a nuanced "U-shaped" dose-response relationship, suggesting an optimal range balancing efficacy and the risk of overtraining. These findings advocate for tailored exercise programs in PD management, emphasizing personalized prescriptions to maximize outcomes.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024506968).

Haploidentical versus mismatched unrelated donor HCT: HLA-factors and donor age considerations.

HLA-mismatched unrelated donors and haploidentical related donors are suitable stem cell sources for hematopoietic cell transplantation (HCT) when patients lack HLA-matched donors. Clinical outcome after mismatched HCT is influenced by HLA factors including the similarity of peptide-binding motifs (PBMs) between the patient and unrelated donor, and of the HLA-B leader in unrelated and haploidentical donors. Whether these factors can aid in the selection between mismatched unrelated and haploidentical donors is not known. To address this question, we investigated outcomes between the two donor types defined by matching for the PBM and leader peptide. We compared PBM-matched (n=614) and mismatched (n=958) MMUDs with calcineurin-inhibitor-based prophylaxis to four haploidentical groups that received post-transplant cyclophosphamide (PTCy)-based prophylaxis. The haploidentical groups were B-leader matched/DRB1-mismatched (n=722), B-leader matched/DRB1-matched (n=154), B-leader mismatched/DRB1-mismatched (n=493), and B-leader mismatched/DRB1-matched (n=63). Multivariate analysis showed that the B-leader matched/DRB1-mismatched haploidentical group had the best overall survival (OS) compared to the PBM-matched MMUD, while other haploidentical groups had comparable OS. The PBM-mismatched MMUD showed the poorest outcomes, similar to the B-leader mismatched/DRB1-matched haploidentical group. Among non-HLA factors, donor age was the most significant predictor of OS. These results suggest that a B-leader matched/DRB1 mismatched haploidentical donor might be the preferred choice among donors of similar age. If such a donor is not available, the youngest donor from either PBM-matched unrelated or other haploidentical groups could be a beneficial choice. These findings need validation with both donor groups receiving PTCy-based GVHD prophylaxis.

Repurposing cyclovirobuxine D as a novel inhibitor of colorectal cancer progression via modulating the CCT3/YAP axis.

BACKGROUND AND PURPOSE: Colorectal cancer (CRC) ranks second in mortality worldwide and requires effective and affordable remedies. Cyclovirobuxine D (CVB-D) is the main effective component of Huangyangning tablet, an approved traditional patent medicine, which is mainly used for cardiovascular treatment. As a multibioactive natural compound, CVB-D possesses underlying anticancer activities. EXPERIMENTAL APPROACH: Cell viability and clone-forming ability were determined in human CRC lines. Western blot, immunofluorescence assay, transmission electron microscopy and senescence-associated ß-galactosidase (SA-ß-Gal) staining were utilized to investigate cell autophagy and senescence. The molecular mechanisms were explored by virtual prediction and experimental validation. Patient-derived xenograft (PDX), dextran sulfate sodium salt (DSS), and azomethane (AOM)/DSS mouse models were employed for in vivo studies. KEY RESULTS: CVB-D inhibited the growth and development of advanced CRC cells / mice by inducing autophagic and senescent activities through the chaperonin containing TCP1 subunit 3 (CCT3)/yes-associated protein (YAP) axis. CVB-D acted as a promising inhibitor of CCT3 by interacting with its ATP site. In PDX tumours, CVB-D showed potential therapeutic effects by targeting CCT3. Treatment with CVB-D alleviated the mouse model of colitis induced by DSS and attenuated AOM/DSS-induced formation of adenomatous polyps by its action on CCT3. CONCLUSIONS AND IMPLICATIONS: Our study has provided a scientific basis for the suggestion that CVB-D may be recognized as a prospective drug candidate for the therapy of CRC in patients.

Study on factors influencing carbon dioxide emissions and carbon peak heterogenous pathways in Chinese provinces.

Implementing a Carbon Peak Action Plan at the regional level requires comprehensive consideration of the developmental heterogeneity among different provinces, which is an effective pathway for China to realize the goal of carbon peak by 2030. However, there is currently no clear provincial roadmap for carbon peak, and existing studies on carbon peak pathways inadequately address provincial heterogeneity. Therefore, this paper employs the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model to decompose assess 8 factors influencing carbon emissions of 30 provinces. According to scenario analysis, the paper explores the differentiated pathways for provincial carbon peaks based on policy expectation indicators (including population, economy, and urbanization rate) and comprises policy control indicators (including the energy structure, energy efficiency, industrial structure, transportation structure, and innovation input). The results indicate that population, per capita GDP, urbanization rate, and innovation input are the primary factors for influencing (negatively) the growth of carbon emissions. In contrast, the optimization and upgrading of the industrial structure, energy intensity, energy structure, and transportation structure have mitigating effects on carbon emissions, especially for the first two factors. The forecasting results reveal that robust regulations of the energy and industry can effectively accelerate carbon peak at a reduced magnitude. If developed at BAU, China cannot achieve carbon peak by 2030, continuing an upward trend. However, by maximizing the adjustment strength of energy and industrial transformation within the scope of provincial capabilities, China could achieve carbon peak as early as 2025, with a peak of 12.069 billion tons. In this scenario, 24 provinces could achieve carbon peak before 2030. Overall, this study suggests the feasibility of differentiated pathway to achieve carbon peaks in China, exploring the carbon peak potential and paths of 30 provinces, and identifying provinces where carbon peak is more challenging. It also provides a reference for the design of carbon peak roadmaps at both provincial and national levels and offers targeted recommendations for the implementation of differentiated policy strategies for the government.

Synergistic solidification and mechanism research of electrolytic manganese residue and coal fly ash based on C-A-S-H gel material.

Electrolytic manganese residue (EMR) is known for high concentrations of Mn2+, NH4+, and heavy metals. Failure to undergo benign treatment and landfill disposal would undeniably lead to negative impacts on the quality of the surrounding ecological environment. This study sought to mitigate the latent environmental risks associated with EMR using a cooperative solidification/stabilization (S/S) method involving coal fly ash (CFA). Leveraging leaching toxicity tests, the leaching behavior of pollutants in electrolytic manganese residue-based geopolymer materials (EMRGM) was determined. At the same time, mechanistic insights into S/S processes were explored utilizing characterization techniques such as XRF, XRD, FT-IR, SEM-EDS, and XPS. Those results confirmed significant reductions in the leaching toxicities of Mn2+ and NH4+ to 4.64 µg/L and 0.99 mg/L, respectively, with all other heavy metal ions falling within the permissible limits set by relevant standards. Further analysis shows that most of NH4+ volatilizes into the air as NH3, and a small part is fixed in the EMRGM in the form of struvite; in addition to being oxidized to MnOOH and MnO2, Mn2+ will also be adsorbed and wrapped by silicon-aluminum gel together with other heavy metal elements in the form of ions or precipitation. This research undeniably provides a solid theoretical foundation for the benign treatment and resourceful utilization of EMR and CFA, two prominent industrial solid wastes.

Two-tier architecture-based grading for pancreatic cancer outperforms traditional grading.

OBJECTIVES: A novel architecture-based grading system for pancreatic ductal adenocarcinoma (PDAC) is tested against traditional grading. METHODS: A total of 103 PDAC resections were graded by College of American Pathologists/American Joint Committee on Cancer (CAP/AJCC) guidelines and by a system using an architectural pattern (dispersed larger duct = low grade vs dense smaller duct = high grade). Survival analyses and interobserver variability were assessed. In total, 114 cases from a public data set were used for validation. RESULTS: Median overall survivals were 15 and 36 months for architectural high-grade and low-grade cases, respectively (P < .001). Conversely, CAP/AJCC grading showed no survival difference between well-differentiated and moderately differentiated tumors (P = .545). Architecture-based grading remained prognostically significant for recurrence-free survival (P = .004), but CAP/AJCC grading was not (P = .226). Adjusted for stage and margin status, architectural high-grade PDACs showed a hazard ratio of 2.69 relative to low grade (P < .001) for survival. The validation cohort confirmed prognostic differences in overall (P < .001) and recurrence-free survival (P = .027) for the architecture-based system, outperforming CAP/AJCC grading. Architecture-based grading exhibited a Cohen's ĸ value of 0.710 (substantial agreement), superior to traditional grading (0.488, moderate agreement). CONCLUSIONS: Grading PDAC based on architectural pattern results in superior prognostication and reproducibility vs CAP/AJCC grading.

ReMAR: a preoperative CT angiography guided metal artifact reduction framework designed for follow-up CTA of endovascular coiling.

Objective. Follow-up computed tomography angiography (CTA) is necessary for ensuring occlusion effect of endovascular coiling. However, the implanted metal coil will introduce artifacts that have a negative spillover into radiologic assessment.Method. A framework named ReMAR is proposed in this paper for metal artifacts reduction (MARs) from follow-up CTA of patients with coiled aneurysms. It employs preoperative CTA to provide the prior knowledge of the aneurysm and the expected position of the coil as a guidance thus balances the metal artifacts removal performance and clinical feasibility. The ReMAR is composed of three modules: segmentation, registration and MAR module. The segmentation and registration modules obtain the metal coil knowledge via implementing aneurysms delineation on preoperative CTA and alignment of follow-up CTA. The MAR module consisting of hybrid convolutional neural network- and transformer- architectures is utilized to restore sinogram and remove the artifact from reconstructed image. Both image quality and vessel rendering effect after metal artifacts removal are assessed in order to responding clinical concerns.Main results. A total of 137 patients undergone endovascular coiling have been enrolled in the study: 13 of them have complete diagnosis/follow-up records for end-to-end validation, while the rest lacked of follow-up records are used for model training. Quantitative metrics show ReMAR significantly reduced the metal-artifact burden in follow-up CTA. Qualitative ranks show ReMAR could preserve the morphology of blood vessels during artifact removal as desired by doctors.Significance. The ReMAR could significantly remove the artifacts caused by implanted metal coil in the follow-up CTA. It can be used to enhance the overall image quality and convince CTA an alternative to invasive follow-up in treated intracranial aneurysm.

METTL3-mediated NDUFB5 m6A modification promotes cell migration and mitochondrial respiration to promote the wound healing of diabetic foot ulcer.

BACKGROUND: Diabetic foot ulcer (DFU) is the most devastating complication of diabetes mellitus (DM) and plays a major role in disability and death in DM patients. NADH: ubiquinone oxidoreductase subunit B5 (NDUFB5) plays an important role in maintaining mitochondrial respiration, but whether it is involved in regulating the progression of advanced glycation end products (AGEs)-mediated DFU is still unclear. METHODS: Firstly, the role of AGEs on cell viability, migration, and mitochondrial respiration in human umbilical vein endothelial cells (HUVECs) was explored in vitro. Next, NDUFB5 expression was detected in human samples and AGEs-treated HUVECs, and NDUFB5's effect on AGEs-induced HUVECs injury and skin wound in diabetic mice was further clarified. In addition, the role of m6A modification mediated by methyltransferase-like 3 (METTL3) in regulating NDUFB5 expression and AGEs-induced HUVECs injury was investigated. RESULTS: NDUFB5 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs, whereas mitochondrial fusion promoter M1 facilitated cell viability, migration, and mitochondrial oxiadative respiration in NDUFB5 knockdown HUVECs. Meanwhile, NDUFB5 promotes skin wound healing in diabetic mice. Besides, METTL3-mediated m6A modification and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) enhanced NDUFB5 expression in HUVECs. Furthermore, METTL3 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs by increasing NDUFB5. CONCLUSION: METTL3-mediated NDUFB5 m6A modification inhibits AGEs-induced cell injury in HUVECs. METTL3 and NDUFB5 might serve as potential targets for DFU therapy in the future.