Multimodal Data Integration Enhance Longitudinal Prediction of New-Onset Systemic Arterial Hypertension Patients with Suspected Obstructive Sleep Apnea.

Background: It is crucial to accurately predict the disease progression of systemic arterial hypertension in order to determine the most effective therapeutic strategy. To achieve this, we have employed a multimodal data-integration approach to predict the longitudinal progression of new-onset systemic arterial hypertension patients with suspected obstructive sleep apnea (OSA) at the individual level. Methods: We developed and validated a predictive nomogram model that utilizes multimodal data, consisting of clinical features, laboratory tests, and sleep monitoring data. We assessed the probabilities of major adverse cardiac and cerebrovascular events (MACCEs) as scores for participants in longitudinal cohorts who have systemic arterial hypertension and suspected OSA. In this cohort study, MACCEs were considered as a composite of cardiac mortality, acute coronary syndrome and nonfatal stroke. The least absolute shrinkage and selection operator (LASSO) regression and multiple Cox regression analyses were performed to identify independent risk factors for MACCEs among these patients. Results: 448 patients were randomly assigned to the training cohort while 189 were assigned to the verification cohort. Four clinical variables were enrolled in the constructed nomogram: age, diabetes mellitus, triglyceride, and apnea-hypopnea index (AHI). This model accurately predicted 2-year and 3-year MACCEs, achieving an impressive area under the receiver operating characteristic (ROC) curve of 0.885 and 0.784 in the training cohort, respectively. In the verification cohort, the performance of the nomogram model had good discriminatory power, with an area under the ROC curve of 0.847 and 0.729 for 2-year and 3-year MACCEs, respectively. The correlation between predicted and actual observed MACCEs was high, provided by a calibration plot, for training and verification cohorts. Conclusions: Our study yielded risk stratification for systemic arterial hypertension patients with suspected OSA, which can be quantified through the integration of multimodal data, thus highlighting OSA as a spectrum of disease. This prediction nomogram could be instrumental in defining the disease state and long-term clinical outcomes.

Bioinspired Molecular Scalpel for Two-Dimensional Metal-Organic Nanosheet: Design Strategies and Recent Progress.

Ultrathin two-dimensional (2D) metal-organic nanosheets (MONs) have attracted continued attention in the field of advanced functional materials. Their nanoscale thickness, high surface-to-volume ratio, and abundant accessible active sites, are superior advantages compared with their 3D bulk counterparts. Bioinspired molecular scalpel strategy is a promising method for the creation of 2D MONs, and may solve the current shortcomings of MONs synthesis. This review aims to provide a state-of-the-art overview of molecular scalpel strategies and share the results of current development to provide a better solution for MONs synthesis. Different types of molecular scalpel strategies have been systematically summarized. Both mechanisms, advantages and limitations of multiform molecular scalpel strategies have been discussed. Besides, the challenges to be overcome and the question to be solved are also introduced.

An analytic method to investigate hemodynamics of the cardiovascular system: Biventricular system.

Previously, we found analytic solutions for single ventricular system based on the lumped parameter model (LPM). In this study, we generalized the method to biventricular system and derived its analytic solutions. LPM is just a set of differential equations, but it is difficult to solve due to time-varying ventricular elastance and high order. Mathematically, there exist no elementary solutions for time-varying equations. It turns out that instead of differential equations, according to volume conservation, a set of algebraic equations can be carried out. The solutions of the set of equations are just physiological states at end of systolic and diastolic phases such as end systolic/diastolic pressure/volume of left ventricle. As a preliminary application, the method is utilized to deduce the hemodynamic effects of VA ECMO. Left ventricular (LV) distension, a serious complication of VA ECMO, is usually attributed to factors such as increased afterload, inadequate LV unloading, reduced myocardial contractility or aortic valve regurgitation (AR), bronchial and Thebesian return in the absence of aortic valve (AoV) opening. Among these, reduced contractility and AR are strongly associated with LV distension. However, in the absence of reduced contractility or AR, it is less clear whether increased afterload or inadequate LV unloading alone can cause LV distension. This leads to the critical question: under what conditions does LV distension occur in the absence of reduced contractility or AR? The analytic formulas derived in this study give conditions for LV distension. Furthermore, the results show that the analytic hemodynamics are coincident with simulated results.

Downgrading BI-RADS categories in ultrasound using strain elastography and computer-aided diagnosis system: a multicenter, prospective study.

OBJECTIVE: To determine whether adding elastography strain ratio (SR) and a deep learning based computer-aided diagnosis (CAD) system to breast ultrasound (US) can help reclassify Breast Imaging Reporting and Data System (BI-RADS) 3 & 4a-c categories and avoid unnecessary biopsies. METHODS: This prospective, multicenter study included 1049 masses (691 benign, 358 malignant) with assigned BI-RADS 3 & 4a-c between 2020 and 2022. CAD results was dichotomized possibly malignant vs. benign. All patients underwent SR and CAD examinations and histopathological findings were the standard of reference. Reduction of unnecessary biopsies (biopsies in benign lesions) and missed malignancies after reclassified (new BI-RADS 3) with SR and CAD were the outcome measures. RESULTS: Following the routine conventional breast US assessment, 48.6% (336 of 691 masses) underwent unnecessary biopsies. After reclassifying BI-RADS 4a masses (SR cut-off < 2.90, CAD dichotomized possibly benign), 25.62% (177 of 691 masses) underwent an unnecessary biopsies corresponding to a 50.14% (177 vs. 355) reduction of unnecessary biopsies. After reclassification, only 1.72% (9 of 523 masses) malignancies were missed in the new BI-RADS 3 group. CONCLUSION: Adding SR and CAD to clinical practice may show an optimal performance in reclassifying BI-RADS 4a to 3 categories, and 50.14% masses would be benefit by keeping the rate of undetected malignancies with an acceptable value of 1.72%. ADVANCES IN KNOWLEDGE: Leveraging the potential of SR in conjunction with CAD holds immense promise in substantially reducing the biopsy frequency associated with BI-RADS 3 and 4A lesions, thereby conferring substantial advantages upon patients encompassed within this cohort.

Association between early central venous pressure measurement and all-cause mortality in critically ill patients with heart failure: A cohort of 11,241 patients.

Background: The timing of central venous pressure (CVP) measurement may play a crucial role in heart failure management, yet no studies have explored this aspect. Methods: Clinical information pertaining to patients in critical condition with a diagnosis of heart failure was retrieved from the MIMIC-IV database. The association between initial measurements of central venous pressure (CVP) and the incidence of mortality from all causes was analyzed using the Cox proportional hazards approach. Subgroup analysis and propensity score matching were conducted for sensitivity analyses. Results: This study included 11,241 participants (median age, 75 years; 44.70 % female). Utilizing restricted cubic spline and Kaplan-Meier survival analyses, it was determined that prognostic outcomes were better when CVP was measured within the initial 5-h window. Multivariate-adjusted 1-year (HR: 0.69; 95 % CI: 0.61-0.77), 90-day (HR: 0.70; 95 % CI: 0.62-0.80), and 30-day (HR: 0.67; 95 % CI: 0.57-0.78) all-cause mortalities were significantly lower in patients with early CVP measurement, which was proved robustly in subgroup analysis. Subsequent to the application of propensity score matching, a cohort of 1536 matched pairs was established, with the observed mortality rates continuing to be significantly lower among participants who underwent early CVP assessment. Conclusions: Early CVP measurement (within 5 h) demonstrated an independent correlation with a decrease in both immediate and extended all-cause mortality rates among patients in critical condition suffering from heart failure.

The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction.

Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Efficacy and Safety of Azvudine in Patients With COVID-19 in China: A Meta-Analysis of Observational Studies.

BACKGROUND: Azvudine (FNC) is a novel small molecule antiviral drug for treating COVID-19 that is available only on the Chinese market. Despite being recommended for treating COVID-19 by the Chinese guidelines, its efficacy and safety are still unclear. This study aimed to evaluate the protective effect of FNC on COVID-19 outcomes and its safety. METHODS: We followed the PRISMA 2020 guidelines and searched the PubMed, Embase, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI) databases to evaluate studies on the effectiveness of FNC in treating COVID-19 in China, focusing on mortality and overall outcomes. Additionally, its impact on the length of hospital stay (LOHS), time to first nucleic acid negative conversion (T-FNANC), and adverse events was evaluated. The inclusion criterion was that the studies were published from July 2021 to April 10, 2024. This study uses the ROBINS-I tool to assess bias risk and employs the GRADE approach to evaluate the certainty of the evidence. RESULTS: The meta-analysis included 24 retrospective studies involving a total of 11 830 patients. Low-certainty evidence revealed no significant difference in mortality (OR = 0.91, 95% CI: 0.76-1.08) or LOHS (WMD = -0.24, 95% CI: -0.83 to 0.35) between FNC and Paxlovid in COVID-19 patients. Low-certainty evidence shows that the T-FNANC was longer (WMD = 1.95, 95% CI: 0.36-3.53). Compared with the Paxlovid group, low-certainty evidence shows the FNC group exhibited a worse composite outcome (OR = 0.77, 95% CI: 0.63-0.95) and fewer adverse events (OR = 0.63, 95% CI: 0.46-0.85). Compared with supportive treatment, low certainty shows FNC significantly reduced the mortality rate in COVID-19 patients (OR = 0.61, 95% CI: 0.51-0.74) and decreased the composite outcome (OR = 0.67, 95% CI: 0.50-0.91), and very low certainty evidence shows significantly decreased the T-FNANC (WMD = -4.62, 95% CI: -8.08 to -1.15). However, in very low certainty, there was no significant difference in LOHS (WMD = -0.70, 95% CI: -3.32 to 1.91) or adverse events (OR = 1.97, 95% CI: 0.48-8.17). CONCLUSIONS: FNC appears to be a safe and potentially effective treatment for COVID-19 in China, but further research with larger, high-quality studies is necessary to confirm these findings. Due to the certainty of the evidence and the specific context of the studies conducted in China, caution should be exercised when considering whether the results are applicable worldwide. TRIAL REGISTRATION: PROSPERO number: CRD42024520565.

Cu-Doping Layered Double Hydroxides Nanozyme Integrated with Nitric Oxide Donor for Enhanced Antioxidant Therapy in Retinopathy.

The prevalence of retinal neovascular diseases necessitates novel treatments beyond current therapies like laser surgery or anti-VEGF treatments, which often carry significant side effects. A novel therapeutic approach is introduced using copper-containing layered double hydroxides (Cu-LDH) nanozymes integrated with nitric oxide-releasing molecules (GSHNO), forming Cu-LDH@GSHNO aimed at combating oxidative stress within the retinal vascular system. Combination of synthetic chemistry and biological testing, Cu-LDH@GSHNO are synthesized, characterized, and assessed for curative effect in HUVECs and an oxygen-induced retinopathy (OIR) mouse model. The results indicate that Cu-LDH@GSHNO demonstrates SOD-CAT cascade catalytic ability, accompanied with GSH and nitric oxide-releasing capabilities, which significantly reduces oxidative cell damage and restores vascular function, presenting a dual-function strategy that enhances treatment efficacy and safety for retinal vascular diseases. The findings encourage further development and clinical exploration of nanozyme-based therapies, promising a new horizon in therapeutic approaches for managing retinal diseases driven by oxidative stress.

Dosage and organic acid residue of MOG35-55 peptide influences immunopathology and development of BCG induced experimental autoimmune encephalomyelitis (EAE).

Experimental autoimmune encephalomyelitis (EAE) serves as a model for studying multiple sclerosis, with immunization strategies utilizing MOG35-55 peptide, emulsified in adjuvant enriched with mycobacterium tuberculosis (Mtb). This study examined the effects of Bacillus Calmette-Guérin (BCG) as an adjuvant, alongside the impact of MOG35-55 peptide doses and their residual counter ions on EAE development. We found that BCG can be effectively used to induce EAE with similar incidence and severity as heat-killed H37Ra, contingent upon the appropriate MOG35-55 peptide dose. Different immunization doses of MOG35-55 peptide significantly affect EAE development, with higher doses leading to a paradoxical reduction in disease activity, probably due to peripheral tolerance mechanisms. Furthermore, doses of MOG35-55 peptides with acetate showed a more pronounced effect on disease development compared to those containing trifluoroacetic acid (TFA), suggesting the potential influence of residual counter ions on EAE activity. We highlighted the feasibility of applying BCG to the establishment of EAE for the first time. Our findings emphasized the importance of MOG peptide dosage and composition in modulating EAE development, offering insights into the mechanisms of autoimmunity and tolerance. This could have implications for autoimmune disease research and the design of therapeutic strategies.

Comparative effects of different treatments based on the levonorgestrel intrauterine system in endometrial carcinoma and endometrial hyperplasia patients: a network meta-analysis.

OBJECTIVE: Levonorgestrel intrauterine system (LNG-IUS) has been widely used in patients with endometrial carcinoma (EC), endometrial hyperplasia without atypical (EH), and atypical endometrial hyperplasia (AEH). The purpose of our Network meta-analysis (NMA) is to evaluate the efficacy of the treatments based on the LNG-IUS in patients with EC and EH with or without atypical. METHODS: We examined PubMed, EMBASE, Web of Science and the Cochrane Library up to 22 April 2024 to determine studies reporting treatment outcomes in EC and EH patients receiving LNG-IUS therapy, LNG-IUS + metformin (MET), oral progestins (OP), etc. We used EndNote 9 to select studies, Jadad scale and NOS scale to assess quality, stata(16.0) and R (4.3.1) to analysis the data. RESULTS: Overall, 28 studies involving 3752 patients were included in our NMA. As for EH patients, LNG-IUS (RR 1.21; 95% CrI [1.11, 1.34]) and LNG-IUS + MET (RR 323.57; 95% CrI [1.61, 214,223,188.1])] significantly increased CR rate in comparison with OP. Based on SUCRA, LNG-IUS + OP was the best treatment to improve CR(SUCRA = 67.2%) in patients with EC, whereas LNG-IUS + MET was superior in increasing CR (SUCRA = 99.8%) than any other treatments for EH patients. Besides, the ranking based on SUCRA illustrated that LNG-IUS alone was the best choice to raise CR rates (SUCRA = 76.7%) for AEH patients. In head-to-head meta-analysis, OP has a higher progression rate (RR 4, 95% CI 1.89-8.46, p = 0.062; I2 = 71.3%), a higher nausea rate (RR 1.93, 95% CI 1.24-3.01, p = 0.187; I2 = 40.4%) than LNG-IUS in patients with EH. In contrast, LNG-IUS had a irregular vaginal bleeding rates (RR 0.76, 95% CI 0.64-0.90, p = 0.034; I2 = 77.7%) than OP in EH patients. In addition, as for AEH patients, OP has a higher persistence rate (RR 4.31, 95% CI 1.43-13.00, p = 0.93; I2 = 0.0%) than LNG-IUS. CONCLUSION: According to the NMA, LNG-IUS related studies are feasible for conservative therapy in patients with EC and EH with or without atypical. Therefore, concerning the curative effect, we recommend LNG-IUS-based treatments as the best conservative therapy for EC and EH patients. However, future studies require large sample sizes and more outcomes to further evaluate the differences of treatment selections based on LNG-IUS.

The Alfalfa-inpatient-CAT assessment model: a thrombotic risk assessment model for inpatient cancer patients.

PURPOSE: To construct a venous thromboembolism (VTE) risk assessment model specifically for inpatients with cancer. METHOD: Patients were included according to the inclusion criteria. Univariate and multivariate analyses of all variables were included to develop a VTE risk assessment model applicable to the derivation cohort. Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were used to test the fit degree and identification validity of the model. The patient data from separate validation cohorts verified the external population. RESULT: A total of 944 cancer patients were included in this study. Alfalfa-inpatient-CAT model, a risk assessment model for VTE in hospitalized cancer patients, was established, which mainly includes hypertension, surgical history (nearly one month), history of VTE, peripherally inserted central venous catheters (PICC), chemotherapy, PT < 12.85 s, D-dimer ≥ 1.805 µg/mL, hemoglobin ≤ 114.5 g/L, CRP ≥ 7.575 mg/L. Hosmer-Lemeshow test results showed P = 0.353 > 0.05, (χ2 = 8.872, Df = 8). The area under ROC curve was 0.906 [95%CI (0.881-0.930), P < 0.001]. The authenticity evaluation in the model database showed that the risk of thrombosis in the high-risk group (score ≥ 3) was 72.63%, significantly higher than that in the low-risk group (score 0-2) (27.37%) [χ2 = 144.00, Df = 1, P < 0.001]. CONCLUSION: This study developed a new VTE risk assessment model - Alfalfa-inpatient-CAT model - for hospitalized cancer patients at high risk of thrombosis. This model has a good fitting degree and discriminant validity. It is expected to provide some reference for the clinical treatment of inpatients with cancer through continuous optimization.

Promoting neurovascularized bone regeneration with a novel 3D printed inorganic-organic magnesium silicate/PLA composite scaffold.

Critical-size bone defect repair presents multiple challenges, such as osteogenesis, vascularization, and neurogenesis. Current biomaterials for bone repair need more consideration for the above functions. Organic-inorganic composites combined with bioactive ions offer significant advantages in bone regeneration. In our work, we prepared an organic-inorganic composite material by blending polylactic acid (PLA) with 3-aminopropyltriethoxysilane (APTES)-modified magnesium silicate (A-M2S) and fabricated it by 3D printing. With the increase of A-M2S proportion, the hydrophilicity and mineralization ability showed an enhanced trend, and the compressive strength and elastic modulus were increased from 15.29 MPa and 94.61 MPa to 44.30 MPa and 435.77 MPa, respectively. Furthermore, A-M2S/PLA scaffolds not only exhibited good cytocompatibility of bone marrow mesenchymal stem cells (BMSCs), human umbilical vein endothelial cells (HUVECs), and Schwann cells (SCs), but also effectively promoted osteogenesis, angiogenesis, and neurogenesis in vitro. After implanting 10% A-M2S/PLA scaffolds in vivo, the scaffolds showed the most effective repair of cranium defects compared to the blank and control group (PLA). Additionally, they promoted the secretion of proteins related to bone regeneration and neurovascular formation. These results provided the basis for expanding the application of A-M2S and PLA in bone tissue engineering and presented a novel concept for neurovascularized bone repair.

Fundamental Limits in Measuring the Anisotropic Rotational Diffusion of Single Molecules.

Many biophysical techniques, such as single-molecule fluorescence correlation spectroscopy, Förster resonance energy transfer, and fluorescence anisotropy, measure the translation and rotation of biomolecules to quantify molecular processes at the nanoscale. These methods often simplify data analysis by assuming isotropic rotational diffusion, e.g., that molecules wobble within a circular cone. This simplification ignores the anisotropy present in many biological contexts that may cause molecules to exhibit different degrees of diffusion in different directions. Here, we loosen this assumption and establish a theoretical framework for describing and measuring anisotropic rotational diffusion using fluorescence imaging. We show that anisotropic wobble is directly quantified by the eigenvalues of a 3-by-3 positive-semidefinite Hermitian matrix M consisting of the second-order moments of a molecule's transition dipole µ. This formalism enables us to model the influence of unavoidable shot noise using a Hermitian perturbation matrix E; the eigenvalues of E directly bound errors in measurements of wobble via Weyl's inequality. Quantifying various perturbations E reveals that anisotropic wobble measurements are generally more sensitive to errors compared to quantifying isotropic wobble. Moreover, severe shot noise can induce negative eigenvalues in estimates of M, thereby causing the anisotropic wobble measurement to fail. Our analysis, using Fisher information, shows that techniques with worse orientation measurement sensitivity experience stronger perturbations E and require larger signal to background ratios to measure anisotropic rotational diffusion accurately. Our work provides deep insights for improving the state of the art in imaging the orientations and anisotropic rotational diffusion of single molecules.

Development and Validation of a Prediction Model for Thyroid Dysfunction in Patients During Immunotherapy.

OBJECTIVE: This study was designed to develop and validate a predictive model for assessing the risk of thyroid toxicity following treatment with immune checkpoint inhibitors. METHODS: A retrospective analysis was conducted on a cohort of 586 patients diagnosed with malignant tumors who received programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. The patients were randomly divided into training and validation cohorts in a 7:3 ratio. Logistic regression analyses were performed on the training set to identify risk factors of thyroid dysfunction, and a nomogram was developed based on these findings. Internal validation was performed using K-fold cross-validation on the validation set. The performance of the nomogram was assessed in terms of discrimination and calibration. Additionally, decision curve analysis was utilized to demonstrate the decision efficiency of the model. RESULTS: Our clinical prediction model consisted of 4 independent predictors of thyroid immune-related adverse events, namely baseline thyrotropin (TSH, OR = 1.427, 95%CI:1.163-1.876), baseline thyroglobulin antibody (TgAb, OR = 1.105, 95%CI:1.035-1.180), baseline thyroid peroxidase antibody (TPOAb, OR = 1.172, 95%CI:1.110-1.237), and baseline platelet count (platelet, OR = 1.004, 95%CI:1.000-1.007). The developed nomogram achieved excellent discrimination with an area under the curve of 0.863 (95%CI: 0.817-0.909) and 0.885 (95%CI: 0.827-0.944) in the training and internal validation cohorts respectively. Calibration curves exhibited a good fit, and the decision curve indicated favorable clinical benefits. CONCLUSION: The proposed nomogram serves as an effective and intuitive tool for predicting the risk of thyroid immune-related adverse events, facilitating clinicians making individualized decisions based on patient-specific information.

The influence of drying routes on the properties of anisotropic all-cellulose composite foams from post-consumer cotton clothing.

Biopolymer-based functional materials are essential for reducing the carbon footprint and providing high-quality lightweight materials suitable for packaging and thermal insulation. Here, cellulose nanocrystals (CNCs) were efficiently upcycled from post-consumer cotton clothing by TEMPO-mediated oxidation and HCl hydrolysis with a yield of 62% and combined with wood cellulose nanofibrils (CNFs) to produce anisotropic foams by unidirectional freeze-casting followed by freeze drying (FD) or supercritical-drying (SCD). Unidirectional freeze-casting resulted in foams with aligned macropores irrespective of the drying method, but the particle packing in the foam wall was significantly affected by how the ice was removed. The FD foams showed tightly packed and aligned CNC and CNF particles while the SCD foams displayed a more network-like structure in the foam walls. The SCD compared to FD foams had more pores smaller than 300 nm and higher specific surface area but they were more susceptible to moisture-induced shrinkage, especially at relative humidities (RH) > 50%. The FD and SCD foams displayed low radial thermal conductivity, and the FD foams displayed a higher mechanical strength and stiffness in compression in the direction of the aligned particles. Better understanding how drying influences the structural, thermal, mechanical and moisture-related properties of foams based on repurposed cotton is important for the development of sustainable nanostructured materials for various applications.

Lanthanum-loaded geopolymer for phosphate removal from agricultural runoff.

The removal of phosphate from agricultural runoff is of great importance to mitigate an overabundance of nutrients discharging into receiving water bodies, which are susceptible to eutrophication. In this study, a La-loaded geopolymer was produced by adding metakaolin within an alkaline medium, consisting of sodium silicate (Na2SiO3) and sodium hydroxide (NaOH). The ratio of Na2SiO3:NaOH within the geopolymer slurry was manipulated to evaluate its effect on phosphate adsorption capacity. The 1.54 ratio yielded the highest adsorption capacity of 33.65 mg g-1. However, due to structural strength, safety, and economic considerations, the 2.0 ratio was used for the isotherm and kinetic adsorption testing. The La-loaded geopolymer exhibited higher phosphate removal in batch adsorption experiments at an acidic level (pH 4) and elevated temperature (40 °C). Moreover, ionic strength (3.5-20 mM) had a negligible impact on phosphate removal, indicating inner-sphere complexation as the main mechanism of adsorption. Additionally, bicarbonate and humic acid increased phosphate removal, whereas sulfate slightly decreased adsorption capacity. The La-loaded geopolymer was further evaluated using a synthetic agricultural solution, which yielded a Type III adsorption isotherm, demonstrating unrestricted multilayer phosphate adsorption. Results from this study verified the La-loaded geopolymer is a promising adsorbent for phosphate removal from agricultural runoff and underlined the importance of matrix effects on treatment performance.

Brain age prediction using interpretable multi-feature-based convolutional neural network in mild traumatic brain injury.

BACKGROUND: Convolutional neural network (CNN) can capture the structural features changes of brain aging based on MRI, thus predict brain age in healthy individuals accurately. However, most studies use single feature to predict brain age in healthy individuals, ignoring adding information from multiple sources and the changes in brain aging patterns after mild traumatic brain injury (mTBI) were still unclear. METHODS: Here, we leveraged the structural data from a large, heterogeneous dataset (N = 1464) to implement an interpretable 3D combined CNN model for brain-age prediction. In addition, we also built an atlas-based occlusion analysis scheme with a fine-grained human Brainnetome Atlas to reveal the age-sstratified contributed brain regions for brain-age prediction in healthy controls (HCs) and mTBI patients. The correlations between brain predicted age gaps (brain-PAG) following mTBI and individual's cognitive impairment, as well as the level of plasma neurofilament light were also examined. RESULTS: Our model utilized multiple 3D features derived from T1w data as inputs, and reduced the mean absolute error (MAE) of age prediction to 3.08 years and improved Pearson's r to 0.97 on 154 HCs. The strong generalizability of our model was also validated across different centers. Regions contributing the most significantly to brain age prediction were the caudate and thalamus for HCs and patients with mTBI, and the contributive regions were mostly located in the subcortical areas throughout the adult lifespan. The left hemisphere was confirmed to contribute more in brain age prediction throughout the adult lifespan. Our research showed that brain-PAG in mTBI patients was significantly higher than that in HCs in both acute and chronic phases. The increased brain-PAG in mTBI patients was also highly correlated with cognitive impairment and a higher level of plasma neurofilament light, a marker of neurodegeneration. The higher brain-PAG and its correlation with severe cognitive impairment showed a longitudinal and persistent nature in patients with follow-up examinations. CONCLUSION: We proposed an interpretable deep learning framework on a relatively large dataset to accurately predict brain age in both healthy individuals and mTBI patients. The interpretable analysis revealed that the caudate and thalamus became the most contributive role across the adult lifespan in both HCs and patients with mTBI. The left hemisphere contributed significantly to brain age prediction may enlighten us to be concerned about the lateralization of brain abnormality in neurological diseases in the future. The proposed interpretable deep learning framework might also provide hope for testing the performance of related drugs and treatments in the future.

Engineering Bifunctional Galactokinase/Uridyltransferase Chimera for Enhanced UDP-d-Xylose Production.

The biotechnological production of uridine diphosphate-d-xylose (UDP-d-xylose), the glycosyl donor in enzymatic for d-xylose, is an important precursor for advancing glycoengineering research on biopharmaceuticals such as heparin and glycosaminoglycans. Leveraging a recently discovered UDP-xylose salvage pathway, we have engineered a series of bifunctional chimeric biocatalysts derived from Solitalea canadensis galactokinase/uridyltransferase, facilitating the conversion of d-xylose to UDP-d-xylose. This study elucidates the novel assembly of eight fusion protein constructs, differing in domain orientations and linker peptide lengths, to investigate their functional expression in Escherichia coli, resulting in the synthesis of the first bifunctional enzyme that orchestrates a direct transformation from d-xylose to UDP-d-xylose. Fusion constructs with a NH2-GSGGGSGHM-COOH peptide linker demonstrated the highest expression and catalytic tenacity. For the highest catalytic conversion from d-xylose to UDP-d-xylose, we established an optimum pH of 7.0 and a temperature optimum of 30 °C, with an optimal fusion enzyme concentration of 3.3 mg/mL for large-scale UDP-d-xylose production. Insights into ATP and ADP inhibition further helped to optimize the reaction conditions. Testing various ratios of unfused galactokinase and uridyltransferase biocatalysts for UDP-xylose synthesis from d-xylose revealed that a 1:1 ratio was optimal. The K cat/K m value for the NH2-GSGGGSGHM-COOH peptide linker showed a 10% improvement compared with the unfused counterparts. The strategic design of these fusion enzymes efficiently routes for the convenient and efficient biocatalytic synthesis of xylosides in biotechnological and pharmaceutical applications.

Serum 5'-Nucleotidase as a Novel Predictor of Adverse Clinical Outcomes after Percutaneous Coronary Intervention in Patients with Coronary Artery Disease.

Background: The correlation between 5 ' -Nucleotidase ( 5 ' -NT) and the clinical outcomes in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) is not clear. This study aims to clarify this relationship. Methods: The PRACTICE study enrolled 15,250 patients between December 2016 and October 2021. After filtering out those without 5 ' -NT data, a total of 6555 patients were analyzed with a median follow-up of 24 months. Based on the receiver operating characteristic (ROC) curve analysis, a 5 ' -NT level of 5.57 U/L was selected as the optimal cutoff value. All research samples were divided into high-value ( ≥ 5.57 U/L, n = 2346) and low-value groups ( < 5.57 U/L, n = 4209). Key clinical outcomes included all-cause death (ACD), cardiovascular death (CD), major adverse cardiovascular events (MACE), and major adverse cardiovascular and cerebrovascular events (MACCE). After separating patients into high and low value groups, multivariate Cox regression analysis was used to correct for potential confounding variables. Finally, risk ratios and their 95% confidence intervals (CIs) were calculated. Results: During the follow-up period, 129 instances of ACD were recorded-49 cases (1.2%) in the low-value group and 80 cases (3.4%) in the high-value group. Similarly, 102 CDs occurred, including 42 low-value group cases (1.0%) and 60 high-value group cases (2.6%). A total of 363 MACE occurred, including 198 low-value group cases (4.7%) and 165 high-value group cases (7%). A total of 397 cases of MACCE occurred, including 227 low-value group cases (5.4%) and 170 high-value group cases (7.2%). As serum 5 ' -NT increased, the incidence of ACD, CD, MACE and MACCE increased. After multivariate Cox regression, high 5 ' -NT levels were linked with a 1.63-fold increase in ACD risk (hazard ratio [HR] = 2.630, 95% CI: [1.770-3.908], p < 0.001) when compared to low 5 ' -NT patients. Similarly, the risk of CD, MACE, and MACCE increased by 1.298-fold (HR = 2.298, 95% CI: [1.477-3.573], p < 0.001), 41% (HR = 1.410, 95% CI: [1.124-1.768], p = 0.003) and 30.5% (HR = 1.305, 95% CI: [1.049-1.623], p = 0.017), respectively. Conclusions: high serum 5 ' -NT levels were independently correlated with adverse clinical outcomes in CAD patients following PCI, affirming its potential as a prognostic indicator.

Structures of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus virions reveal species-specific tegument and envelope features.

Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are classified into the gammaherpesvirus subfamily of Herpesviridae , which stands out from its alpha- and betaherpesvirus relatives due to the tumorigenicity of its members. Although structures of human alpha- and betaherpesviruses by cryogenic electron tomography (cryoET) have been reported, reconstructions of intact human gammaherpesvirus virions remain elusive. Here, we structurally characterize extracellular virions of EBV and KSHV by deep learning-enhanced cryoET, resolving both previously known monomorphic capsid structures and previously unknown pleomorphic features beyond the capsid. Through subtomogram averaging and subsequent tomogram-guided sub-particle reconstruction, we determined the orientation of KSHV nucleocapsids from mature virions with respect to the portal to provide spatial context for the tegument within the virion. Both EBV and KSHV have an eccentric capsid position and polarized distribution of tegument. Tegument species span from the capsid to the envelope and may serve as scaffolds for tegumentation and envelopment. The envelopes of EBV and KSHV are less densely populated with glycoproteins than those of herpes simplex virus 1 and human cytomegalovirus, representative members of alpha- and betaherpesviruses, respectively. This population density of glycoproteins correlates with their relative infectivity against HEK293T cells. Also, we observed fusion protein gB trimers exist within triplet arrangements in addition to standalone complexes, which is relevant to understanding dynamic processes such as fusion pore formation. Taken together, this study reveals nuanced yet important differences in the tegument and envelope architectures among human herpesviruses and provides insights into their varied cell tropism and infection. Importance: Discovered in 1964, Epstein-Barr virus (EBV) is the first identified human oncogenic virus and the founding member of the gammaherpesvirus subfamily. In 1994, another cancer-causing virus was discovered in lesions of AIDS patients and later named Kaposi's sarcoma-associated herpesvirus (KSHV), the second human gammaherpesvirus. Despite the historical importance of EBV and KSHV, technical difficulties with isolating large quantities of these viruses and the pleiomorphic nature of their envelope and tegument layers have limited structural characterization of their virions. In this study, we employed the latest technologies in cryogenic electron microscopy (cryoEM) and tomography (cryoET) supplemented with an artificial intelligence-powered data processing software package to reconstruct 3D structures of the EBV and KSHV virions. We uncovered unique properties of the envelope glycoproteins and tegument layers of both EBV and KSHV. Comparison of these features with their non-tumorigenic counterparts provides insights into their relevance during infection.