Molecular dynamics study on the thermal properties of DGEBA/DETA/Ag/SWCNT-Ag composite materials.

CONTEXT: Traditional conductive adhesives based on epoxy resin system often encounter problems such as high brittleness and low heat resistance. Therefore, it is particularly important to improve the thermal and mechanical properties of the conductive adhesive. In this study, the effects of SWCNT-Ag and SWCNT fillers on the thermal properties of DGEBA/DETA/Ag conductive adhesive system were studied by using molecular dynamics to construct different cross-linking models. The final results show that the addition of SWCNT and SWCNT-Ag can significantly improve the thermal properties of the conductive adhesive. However, the nanosilver particles on the surface of SWCNT-Ag act as a bridge for the connection between SWCNT and Ag in the conductive adhesive. Therefore, SWCNT-Ag has a more positive impact on the thermal properties of DGEBA/DETA/Ag conductive adhesive system. METHODS: In this paper, the influence of SWCNT-Ag on the thermal properties of traditional DGEBA/DETA/Ag conductive adhesive system was studied by using Materials Studio software. The volume shrinkage, glass transition temperature, thermal expansion coefficient, and thermal conductivity of the material were calculated based on COMPASS force field. The thermal conductivity is calculated by using reverse non-equilibrium molecular dynamics method. Finally, it is found that SWCNT-Ag has a positive effect on the thermal properties of the conductive adhesive system by comparing several groups of calculation data.

MCA Parallel Anatomic Scanning MR Imaging-Guided Recanalization of a Chronic Occluded MCA by Endovascular Treatment.

Basi-parallel anatomic scanning has been widely used for assessing the vascular morphology of vertebral basilar arteries. Previous studies have demonstrated its efficacy in evaluating the morphology of the MCA, which we refer to as MCA parallel anatomic scanning MR imaging (MCPAS). In this study, we present our experience with the application of MCPAS in patients with MCA occlusion. Endovascular treatment was performed on the patients with intact MCA morphology visible in on MCPAS, with no intracranial hemorrhage, occlusion, or other complications observed. No severe stenosis or re-occlusion was observed at the 12-month postoperative follow-up. In conclusion, MCPAS is an effective method for assessing the outer contour of an occlusive MCA. Endovascular treatment can be considered a safe and efficient option for patients who show a favorable MCA through MCPAS assessment.

Dysregulated Wnt/ß-catenin signaling confers resistance to cuproptosis in cancer cells.

Cuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy. However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. Here, we found that cuproptosis activates the Wnt/ß-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/ß-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/ß-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the ß-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis. Knockdown of TCF4 or pharmacological Wnt/ß-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/ß-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.

Pipette-tip solid-phase extraction coupled with matrix-assisted laser desorption/ionization mass spectrometry enables rapid and high-throughput analysis of antidepressants in rat serum.

Therapeutic drug monitoring is essential for ensuring the efficacy and safety of medications. This study introduces a streamlined approach that combines pipette-tip solid-phase extraction (PT-SPE) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), facilitating rapid and high-throughput monitoring of drug concentrations. As a demonstration, this method was applied to the extraction and quantification of antidepressants in serum. Utilizing Zip-Tip C18, the method enabled the extraction of antidepressants from complex biological matrices in less than 2 min, with the subsequent MALDI-MS analysis yielding results in just 1 min. Optimal extraction recoveries were achieved using a sampling solution at pH 9.0 and a 10 µL ethanol desorption solution containing 0.1% phosphoric acid. For MALDI analysis, 2,5-dihydroxybenzoic acid was identified as the most effective matrix for producing the highest signal intensity. The quantification strategy exhibited robust linearities (R2 ≥ 0.997) and satisfactory limits of quantification, ranging from 0.05 to 0.5 µg/mL for a suite of antidepressants. The application for monitoring dynamic concentration changes of antidepressants in rat serum emphasized the method's efficacy. This strategy offers the advantages of high throughput, minimal sample usage, environmental sustainability, and simplicity, providing ideas and a reference basis for the subsequent development of methods for therapeutic drug monitoring.

Super-resolution diffractive neural network for all-optical direction of arrival estimation beyond diffraction limits.

Wireless sensing of the wave propagation direction from radio sources lays the foundation for communication, radar, navigation, etc. However, the existing signal processing paradigm for the direction of arrival estimation requires the radio frequency electronic circuit to demodulate and sample the multichannel baseband signals followed by a complicated computing process, which places the fundamental limit on its sensing speed and energy efficiency. Here, we propose the super-resolution diffractive neural networks (S-DNN) to process electromagnetic (EM) waves directly for the DOA estimation at the speed of light. The multilayer meta-structures of S-DNN generate super-oscillatory angular responses in local angular regions that can perform the all-optical DOA estimation with angular resolutions beyond the diffraction limit. The spatial-temporal multiplexing of passive and reconfigurable S-DNNs is utilized to achieve high-resolution DOA estimation over a wide field of view. The S-DNN is validated for the DOA estimation of multiple radio sources over 5 GHz frequency bandwidth with estimation latency over two to four orders of magnitude lower than the state-of-the-art commercial devices in principle. The results achieve the angular resolution over an order of magnitude, experimentally demonstrated with four times, higher than diffraction-limited resolution. We also apply S-DNN's edge computing capability, assisted by reconfigurable intelligent surfaces, for extremely low-latency integrated sensing and communication with low power consumption. Our work is a significant step towards utilizing photonic computing processors to facilitate various wireless sensing and communication tasks with advantages in both computing paradigms and performance over electronic computing.

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in autoimmune rheumatic diseases: a brief research report from a Mendelian randomization study.

Background: Currently, the association between the consumption of polyunsaturated fatty acids (PUFAs) and the susceptibility to autoimmune rheumatic diseases (ARDs) remains conflict and lacks substantial evidence in various clinical studies. To address this issue, we employed Mendelian randomization (MR) to establish causal links between six types of PUFAs and their connection to the risk of ARDs. Methods: We retrieved summary-level data on six types of PUFAs, and five different types of ARDs from publicly accessible GWAS statistics. Causal relationships were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the reliability of our research findings, we used four complementary approaches and conducted multivariable MR analysis (MVMR). Additionally, we investigated reverse causality through a reverse MR analysis. Results: Our results indicate that a heightened genetic predisposition for elevated levels of EPA (ORIVW: 0.924, 95% CI: 0.666-1.283, P IVW = 0.025) was linked to a decreased susceptibility to psoriatic arthritis (PsA). Importantly, the genetically predicted higher levels of EPA remain significantly associated with an reduced risk of PsA, even after adjusting for multiple testing using the FDR method (P IVW-FDR-corrected = 0.033) and multivariable MR analysis (P MV-IVW < 0.05), indicating that EPA may be considered as the risk-protecting PUFAs for PsA. Additionally, high levels of LA showed a positive causal relationship with a higher risk of PsA (ORIVW: 1.248, 95% CI: 1.013-1.538, P IVW = 0.037). It is interesting to note, however, that the effects of these associations were weakened in our MVMR analyses, which incorporated adjustment for lipid profiles (P MV-IVW > 0.05) and multiple testing using the FDR method (P IVW-FDR-corrected = 0.062). Moreover, effects of total omega-3 PUFAs, DHA, EPA, and LA on PsA, were massively driven by SNP effects in the FADS gene region. Furthermore, no causal association was identified between the concentrations of other circulating PUFAs and the risk of other ARDs. Further analysis revealed no significant horizontal pleiotropy and heterogeneity or reverse causality. Conclusion: Our comprehensive MR analysis indicated that EPA is a key omega-3 PUFA that may protect against PsA but not other ARDs. The FADS2 gene appears to play a central role in mediating the effects of omega-3 PUFAs on PsA risk. These findings suggest that EPA supplementation may be a promising strategy for preventing PsA onset. Further well-powered epidemiological studies and clinical trials are warranted to explore the potential mechanisms underlying the protective effects of EPA in PsA.

miR-20a: a key regulator of orthodontic tooth movement via BMP2 signaling pathway modulation.

AIM: In this study, we aimed to establish a rat tooth movement model to assess miR-20's ability in enhancing the BMP2 signaling pathway and facilitate alveolar bone remodeling. METHOD: 60 male SD rats had nickel titanium spring devices placed between their left upper first molars and incisors, with the right side serving as the control. Forces were applied at varying durations (18h, 24h, 30h, 36h, 42h, 1d, 3d, 5d, 7d, 14d), and their bilateral maxillary molars and surrounding alveolar bones were retrieved for analysis. Fluorescent quantitative PCR was conducted to assess miR-20a, BMP2, Runx2, Bambi and Smad6 gene expression in alveolar bone, and western blot was performed to determine the protein levels of BMP2, Runx2, Bambi, and Smad6 after mechanical loading. RESULT: We successfully established an orthodontic tooth movement model in SD rats and revealed upregulated miR-20a expression and significantly increased BMP2 and Runx2 gene expression and protein synthesis in alveolar bone during molar tooth movement. Although Bambi and Smad6 gene expression did not significantly increase, their protein synthesis was found to decrease significantly. CONCLUSION: MiR-20a was found to be involved in rat tooth movement model alveolar bone remodeling, wherein it promoted remodeling by reducing Bambi and Smad6 protein synthesis through the BMP2 signaling pathway.

Harnessing cerium-based biomaterials for the treatment of bone diseases.

Bone, an actively metabolic organ, undergoes constant remodeling throughout life. Disturbances in the bone microenvironment can be responsible for pathologically bone diseases such as periodontitis, osteoarthritis, rheumatoid arthritis and osteoporosis. Conventional bone tissue biomaterials are not adequately adapted to complex bone microenvironment. Therefore, there is an urgent clinical need to find an effective strategy to improve the status quo. In recent years, nanotechnology has caused a revolution in biomedicine. Cerium(III, IV) oxide, as an important member of metal oxide nanomaterials, has dual redox properties through reversible binding with oxygen atoms, which continuously cycle between Ce(III) and Ce(IV). Due to its special physicochemical properties, cerium(III, IV) oxide has received widespread attention as a versatile nanomaterial, especially in bone diseases. This review describes the characteristics of bone microenvironment. The enzyme-like properties and biosafety of cerium(III, IV) oxide are also emphasized. Meanwhile, we summarizes controllable synthesis of cerium(III, IV) oxide with different nanostructural morphologies. Following resolution of synthetic principles of cerium(III, IV) oxide, a variety of tailored cerium-based biomaterials have been widely developed, including bioactive glasses, scaffolds, nanomembranes, coatings, and nanocomposites. Furthermore, we highlight the latest advances in cerium-based biomaterials for inflammatory and metabolic bone diseases and bone-related tumors. Tailored cerium-based biomaterials have already demonstrated their value in disease prevention, diagnosis (imaging and biosensors) and treatment. Therefore, it is important to assist in bone disease management by clarifying tailored properties of cerium(III, IV) oxide in order to promote the use of cerium-based biomaterials in the future clinical setting. STATEMENT OF SIGNIFICANCE: In this review, we focused on the promising of cerium-based biomaterials for bone diseases. We reviewed the key role of bone microenvironment in bone diseases and the main biological activities of cerium(III, IV) oxide. By setting different synthesis conditions, cerium(III, IV) oxide nanostructures with different morphologies can be controlled. Meanwhile, tailored cerium-based biomaterials can serve as a versatile toolbox (e.g., bioactive glasses, scaffolds, nanofibrous membranes, coatings, and nanocomposites). Then, the latest research advances based on cerium-based biomaterials for the treatment of bone diseases were also highlighted. Most importantly, we analyzed the perspectives and challenges of cerium-based biomaterials. In future perspectives, this insight has given rise to a cascade of cerium-based biomaterial strategies, including disease prevention, diagnosis (imaging and biosensors) and treatment.

Factors Affecting the Effectiveness and Safety of Polymyxin B in the Treatment of Gram-negative Bacterial Infections: A Meta-Analysis of 96 Articles.

PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A Model-Based Meta-Analysis (MBMA) of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-day survival rates. RESULTS: In the study involving 96 articles and 9,716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% CI: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), p=0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), p<0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, p=0.54. The 30-day Overall Survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of Polymyxin B doesn't significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like Pseudomonas aeruginosa are associated with higher mortality. Combining Polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.

Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity.

Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.

Phosphorus uptake and rhizosphere properties of alfalfa in response to phosphorus fertilizer types in sandy soil and saline-alkali soil.

Introduction: Phosphorus (P) fertilizer is critical to maintain a high yield and quality of alfalfa (Medicago sativa L.). There are several fertilizer types and soil types in China, and the application of a single type of P fertilizer may not be suitable for present-day alfalfa production. Methods: In order to select the optimal combination of alfalfa and soil type and fertilizer type for improving P utilization efficiency. We conducted a greenhouse pot experiment, calcium superphosphate (SSP), diammonium phosphate (DAP), ammonium polyphosphate (APP), potassium dihydrogen phosphate (KP), and no-fertilizer control treatments were applied to alfalfa in sandy and saline-alkali soils. The response of alfalfa root morphology and rhizosphere processes to different P fertilizers was investigated. Results and discussion: The results showed that shoot biomass of alfalfa was slightly higher in sandy soil than in saline-alkali soil. Shoot biomass of alfalfa increased by 223%-354% in sandy soil under P treatments compared with the control, and total root length increased significantly by 74% and 53% in DAP and SSP treatments, respectively. In saline-alkali soil, alfalfa shoot biomass was significantly increased by 229% and 275% in KP and DAP treatments, and total root length was increased by 109% only in DAP treatment. Net P uptake of alfalfa in DAP treatment was the highest in both soils, which were 0.73 and 0.54 mg plant-1, respectively. Alfalfa shoot P concentration was significantly positively correlated with shoot and root biomass (P < 0.05, 0.01 or 0.001) whereas negatively correlated with acid phosphatase concentration (P < 0.05). Improvement of plant growth and P uptake induced by P fertilizer application was greater in sandy soil than in saline-alkali soil. DAP and KP was the most efficient P fertilizers in both sandy soil and saline-alkali soil.

CT-based radiomics analysis of different machine learning models for differentiating gnathic fibrous dysplasia and ossifying fibroma.

OBJECTIVE: In this study, our aim was to develop and validate the effectiveness of diverse radiomic models for distinguishing between gnathic fibrous dysplasia (FD) and ossifying fibroma (OF) before surgery. MATERIALS AND METHODS: We enrolled 220 patients with confirmed FD or OF. We extracted radiomic features from nonenhanced CT images. Following dimensionality reduction and feature selection, we constructed radiomic models using logistic regression, support vector machine, random forest, light gradient boosting machine, and eXtreme gradient boosting. We then identified the best radiomic model using receiver operating characteristic (ROC) curve analysis. After combining radiomics features with clinical features, we developed a comprehensive model. ROC curve and decision curve analysis (DCA) demonstrated the models' robustness and clinical value. RESULTS: We extracted 1834 radiomic features from CT images, reduced them to eight valuable features, and achieved high predictive efficiency, with area under curves (AUC) exceeding 0.95 for all the models. Ultimately, our combined model, which integrates radiomic and clinical data, displayed superior discriminatory ability (AUC: training cohort 0.970; test cohort 0.967). DCA highlighted its optimal clinical efficacy. CONCLUSION: Our combined model effectively differentiates between FD and OF, offering a noninvasive and efficient approach to clinical decision-making.

Comparison between left bundle branch area pacing and right ventricular pacing: ventricular electromechanical synchrony and risk of atrial high-rate episodes.

Background: The electromechanical dyssynchrony associated with right ventricular pacing (RVP) has been found to have adverse impact on clinical outcomes. Several studies have shown that left bundle branch area pacing (LBBAP) has superior pacing parameters compared with RVP. We aimed to assess the difference in ventricular electromechanical synchrony and investigate the risk of atrial high-rate episodes (AHREs) in patients with LBBAP and RVP. Methods: We consecutively identified 40 patients with atrioventricular block and no prior atrial fibrillation. They were divided according to the ventricular pacing sites: the LBBAP group and the RVP group (including the right ventricular apical pacing (RVA) group and the right side ventricular septal pacing (RVS) group). Evaluation of ventricular electromechanical synchrony was implemented using electrocardiogram and two-dimensional speckle tracking echocardiography (2D-STE). AHRE was defined as event with an atrial frequency of ≥176 bpm lasting for ≥6 min recorded by pacemakers during follow-up. Results: The paced QRS duration of the LBBAP group was significantly shorter than that of the other two groups: LBBAP 113.56 ± 9.66 ms vs. RVA 164.73 ± 14.49 ms, p < 0.001; LBBAP 113.56 ± 9.66 ms vs. RVS 148.23 ± 17.3 ms, p < 0.001. The LBBAP group showed shorter maximum difference (TDmax), and standard deviation (SD) of the time to peak systolic strain among the 18 left ventricular segments, and time of septal-to-posterior wall motion delay (SPWMD) compared with the RVA group (TDmax, 87.56 ± 56.01 ms vs. 189.85 ± 91.88 ms, p = 0.001; SD, 25.40 ± 14.61 ms vs. 67.13 ± 27.40 ms, p < 0.001; SPWMD, 28.75 ± 21.89 ms vs. 99.09 ± 46.56 ms, p < 0.001) and the RVS group (TDmax, 87.56 ± 56.01 ms vs. 156.46 ± 55.54 ms, p = 0.003; SD, 25.40 ± 14.61 ms vs. 49.02 ± 17.85 ms, p = 0.001; SPWMD, 28.75 ± 21.89 ms vs. 91.54 ± 26.67 ms, p < 0.001). The interventricular mechanical delay (IVMD) was shorter in the LBBAP group compared with the RVA group (-5.38 ± 9.31 ms vs. 44.82 ± 16.42 ms, p < 0.001) and the RVS group (-5.38 ± 9.31 ms vs. 25.31 ± 21.36 ms, p < 0.001). Comparing the RVA group and the RVS group, the paced QRS duration and IVMD were significantly shorter in the RVS group (QRS duration, 164.73 ± 14.49 ms vs. 148.23 ± 17.3 ms, p = 0.02; IVMD, 44.82 ± 16.42 ms vs. 25.31 ± 21.36 ms, p = 0.022). During follow-up, 2/16 (12.5%) LBBAP patients, 4/11 (36.4%) RVA patients, and 8/13 (61.5%) RVS patients had recorded novel AHREs. LBBAP was proven to be independently associated with decreased risk of AHREs than RVP (log-rank p = 0.043). Conclusion: LBBAP generates narrower paced QRS and better intro-left ventricular and biventricular contraction synchronization compared with traditional RVP. LBBAP was associated with a decreased risk of AHREs compared with RVP.

Tuning cellular metabolism for cancer virotherapy.

Oncolytic viruses (OVs) represent an emerging immunotherapeutic strategy owing to their capacity for direct tumor lysis and induction of antitumor immunity. However, hurdles like transient persistence and moderate efficacy necessitate innovative approaches. Metabolic remodeling has recently gained prominence as a strategic intervention, wherein OVs or combination regimens could reprogram tumor and immune cell metabolism to enhance viral replication and oncolysis. In this review, we summarize recent advances in strategic reprogramming of tumor and immune cell metabolism to enhance OV-based immunotherapies. Specific tactics include engineering viruses to target glycolytic, glutaminolytic, and nucleotide synthesis pathways in cancer cells, boosting viral replication and tumor cell death. Additionally, rewiring T cell and NK cell metabolism of lipids, amino acids, and carbohydrates shows promise to enhance antitumor effects. Further insights are discussed to pave the way for the clinical implementation of metabolically enhanced oncolytic platforms, including balancing metabolic modulation to limit antiviral responses while promoting viral persistence and tumor clearance.

Heterogeneity of myeloid cells in common cancers: Single cell insights and targeting strategies.

Tumor microenvironment (TME), is characterized by a complex and heterogenous composition involving a substantial population of immune cells. Myeloid cells comprising over half of the solid tumor mass, are undoubtedly one of the most prominent cell populations associated with tumors. Studies have unambiguously established that myeloid cells play a key role in tumor development, including immune suppression, pro-inflammation, promote tumor metastasis and angiogenesis, for example, tumor-associated macrophages promote tumor progression in a variety of common tumors, including lung cancer, through direct or indirect interactions with the TME. However, due to previous technological constraints, research on myeloid cells often tended to be conducted as studies with low throughput and limited resolution. For example, the conventional categorization of macrophages into M1-like and M2-like subsets based solely on their anti-tumor and pro-tumor roles has disregarded their continuum of states, resulting in an inadequate analysis of the high heterogeneity characterizing myeloid cells. The widespread adoption of single-cell RNA sequencing (scRNA-seq) in tumor immunology has propelled researchers into a new realm of understanding, leading to the establishment of novel subsets and targets. In this review, the origin of myeloid cells in high-incidence cancers, the functions of myeloid cell subsets examined through traditional and single-cell perspectives, as well as specific targeting strategies, are comprehensively outlined. As a result of this endeavor, we will gain a better understanding of myeloid cell heterogeneity, as well as contribute to the development of new therapeutic approaches.

Development and validation of a nomogram model for all-cause mortality risk in patients with chronic heart failure and atrial fibrillation.

BACKGROUND: As the global aging process continues to accelerate, heart failure (HF) has become an important cause of increased morbidity and mortality in elderly patients. Chronic atrial fibrillation (AF) is a major risk factor for HF. Patients with HF combined with AF are more difficult to treat and have a worse prognosis. The aim of this study was to explore the risk factors for 1-year mortality in patients with HF combined with AF and to develop a risk prediction assessment model. METHODS: We recruited hospitalized patients with HF and AF who received standardized care in the Department of Cardiology at Shengjing Hospital of China Medical University from January 2013 to December 2018. The patients were randomly divided into modeling and internal validation groups using a random number generator at a 1:1 ratio. Multivariate Cox regression analysis was used to identify risk factors for all-cause mortality during a one-year follow-up period. Then, a nomogram was constructed based on the weights of each index and validated. Receiver operating characteristic curve, the area under the curve (AUC), decision curve, and calibration curve analyses for survival were used to evaluate the model's predictive and clinical validities and calibration. RESULTS: We included 3,406 patients who met the eligibility criteria; 1,703 cases each were included in the modeling and internal validation groups. Eight statistically significant predictors were identified: age, sex, New York Heart Association cardiac function class III or IV, a history of myocardial infarction, and the albumin, triglycerides, N-terminal pro-b-type natriuretic peptide, and blood urea nitrogen levels. The AUCs were 0.793 (95% confidence interval: 0.763-0.823) and 0.794 (95% confidence interval: 0.763-0.823) in the modeling and validation cohorts, respectively. CONCLUSIONS: We present a predictive model for all-cause mortality in patients with coexisting HF and AF comprising eight key factors. This model gives clinicians a simple assessment tool that may improve the clinical management of these patients.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

T cell exhaustion initiates tertiary lymphoid structures and turbocharges cancer-immunity cycle.

Immune therapies represented by immune checkpoint blockade (ICB) have significantly transformed cancer treatment. However, the effectiveness of these treatments depends on the status of T cells. T cell exhaustion, characterized by diminished effector function, increased expression of co-inhibitory receptors, and clonal deletion, emerges as a hypofunctional state resulting from chronic exposure to antigens, posing an obstacle to ICB therapy. Several studies have deeply explored T cell exhaustion, providing innovative insights and correlating T cell exhaustion with tertiary lymphoid structures (TLS) formation. TLS, lymphocyte aggregates formed in non-lymphoid tissues amid chronic inflammation, serve as pivotal reservoirs for anti-tumour immunity. Here, we underscore the pivotal role of T cell exhaustion as a signalling mechanism in reinvigorating anti-tumour immunity by turbocharging cancer-immunity (CI) cycle, particularly when tumour becomes unmanageable. Building upon this concept, we summarize emerging immunotherapeutic strategies aimed at enhancing the response rate to ICB therapy and improving patient prognosis.

Meta-Analysis of Rice Phosphoproteomics Data to Understand Variation in Cell Signaling Across the Rice Pan-Genome.

Phosphorylation is the most studied post-translational modification, and has multiple biological functions. In this study, we have reanalyzed publicly available mass spectrometry proteomics data sets enriched for phosphopeptides from Asian rice (Oryza sativa). In total we identified 15,565 phosphosites on serine, threonine, and tyrosine residues on rice proteins. We identified sequence motifs for phosphosites, and link motifs to enrichment of different biological processes, indicating different downstream regulation likely caused by different kinase groups. We cross-referenced phosphosites against the rice 3,000 genomes, to identify single amino acid variations (SAAVs) within or proximal to phosphosites that could cause loss of a site in a given rice variety and clustered the data to identify groups of sites with similar patterns across rice family groups. The data has been loaded into UniProt Knowledge-Base─enabling researchers to visualize sites alongside other data on rice proteins, e.g., structural models from AlphaFold2, PeptideAtlas, and the PRIDE database─enabling visualization of source evidence, including scores and supporting mass spectra.

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.