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Alzheimer's disease (AD) is complicated by multiple environmental and polygenetic factors. The accuracy of artificial neural networks (ANNs) incorporating the common factors for identifying AD has not been evaluated. A total of 184 probable AD patients and 3773 healthy individuals aged 65 and over were enrolled. AD-related genes (51 SNPs) and 8 environmental factors were selected as features for multilayer ANN modeling. Random Forest (RF) and Support Vector Machine with RBF kernel (SVM) were also employed for comparison. Model results were verified using traditional statistics. The ANN achieved high accuracy (0.98), sensitivity (0.95), and specificity (0.96) in the intrinsic test for AD classification. Excluding age and genetic data still yielded favorable results (accuracy: 0.97, sensitivity: 0.94, specificity: 0.96). The assigned weights to ANN features highlighted the importance of mental evaluation, years of education, and specific genetic variations (CASS4 rs7274581, PICALM rs3851179, and TOMM40 rs2075650) for AD classification. Receiver operating characteristic analysis revealed AUC values of 0.99 (intrinsic test), 0.60 (TWB-GWA), and 0.72 (CG-WGS), with slightly lower AUC values (0.96, 0.80, 0.52) when excluding age in ANN. The performance of the ANN model in AD classification was comparable to RF, SVM (linear kernel), and SVM (RBF kernel). The ANN model demonstrated good sensitivity, specificity, and accuracy in AD classification. The top-weighted SNPs for AD prediction were CASS4 rs7274581, PICALM rs3851179, and TOMM40 rs2075650. The ANN model performed similarly to RF and SVM, indicating its capability to handle the complexity of AD as a disease entity. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infection remains a major problem. The bactericidal efficacy of commercial irrigation solutions for the treatment of infection is not well established in the presence of porous titanium (Ti) implants. This study compared the in vitro efficacy of five irrigation solutions on infected three-dimensional–printed porous Ti discs. Titanium discs (2 × 4 mm, 400, 700, and 1,000 μm) were infected with S. aureus (1 × 106 colony-forming unit/mL) and incubated for 3 hours or 3 days to create acute or chronic infection with biofilm. Discs were irrigated with saline, antibiotic, or antiseptic solutions, then repeatedly sonicated. Sonicates were cultured for bacterial quantification. Statistical analyses were performed using one-way analysis of variance (ANOVA), followed by Tukey-Kramer post hoc testing (P <.05 significance). Biofilms were visualized by scanning electron microscopy. Saline irrigation was ineffective in both groups. In acute infections with 400 μm pores, differences were found with saline versus solution #3 (P =.015) and #4 (P =.015). Solution #4 had the lowest bacterial counts for all pore sizes. For biofilm, irrigation with saline, solutions #1, #2, and #3 inadequately cleared bacteria in all pore sizes. Lower remaining concentrations were observed in #4 with 400μm pores compared to saline (P =.06) and #2 (P =.039). The scanning electron microscopy showed a reduction of biofilm in samples washed with #4. Irrigation of infected porous Ti discs with saline, solutions #1 and #2 failed to reduce the bacterial load. The 400 μm discs consistently had more bacteria despite irrigation, highlighting the difficulty of removing bacteria from small pores. Solutions #3 and #4 reduced bacteria acutely, but only #4 demonstrated efficacy in clearing biofilm compared to saline. These results should be considered when treating periprosthetic joint infection in the presence of porous components and the potential presence of biofilm. [ABSTRACT FROM AUTHOR]

Optimal position of total hip arthroplasty (THA) components is critical for joint mechanics and stability. Acetabular component positioning during supine surgery in direct anterior approach (DAA) THA may be different in the standing position postoperatively, which traditional fluoroscopy is unable to predict. A novel 3-dimensional (3D) image analysis technology (IAT) that uses artificial intelligence to measure the tilt and rotation of the pelvis has enabled prediction of component positioning from supine to standing. The purpose of this study was to compare intraoperative fluoroscopy, non–3D-IAT, and 3D-IAT with postoperative standing radiographs to assess the accuracy of component positioning. From 2022 to 2023, 30 consecutive patients (86.6% women, mean age 59 [range, 55 to 67]) undergoing primary DAA THA with the use of the 3D-IAT were identified. A separate cohort of 148 patients from 2020 to 2021 (85% women, mean age 65 [range, 55 to 69]) who underwent DAA THA with non–3D-IAT was used for comparison. Leg length discrepancy (LLD), cup anteversion, and inclination were manually measured on intraoperative fluoroscopic images and digitally measured using IAT. Follow-up evaluation occurred at 1 month with standing pelvis radiographs measured using Ein Bild Röntgen Analyze–Cup software. Measurements were compared via Wilcoxon signed rank tests where P ≤.05 indicates significantly different measurements. Median LLD, inclination, and anteversion measurements via non–3D-IAT and fluoroscopy were significantly different compared to postoperative standing radiographs (P <.001). The 3D-IAT more accurately predicted LLD, abduction, and anteversion, with values not significantly different from postoperative standing measurements (P =.23, P =.93, and P =.36, respectively). The use of the 3D-IAT during DAA THA allowed for the more accurate prediction of acetabular component position in the standing position postoperatively. [ABSTRACT FROM AUTHOR]

Objective: To three-dimensionally evaluate the position and morphology of the TMJ in skeletal Class I with variable degrees of overbite and overjet in comparison with normal peers. Methods: Pretreatment CBCT scans of 126 adults were retrieved. Based on the severity of overjet and overbite, the sample was divided into three main groups and six subgroups (18 patients each): the first group with a normal overbite and variable overjet degree and the second group with normal overjet and variable overbite degree. These six subgroups were compared with a third control group of normal overjet and overbite. Results: There were significant differences in vertical condylar position, vertical and anteroposterior condylar inclinations, condylar height, and significant posterior condylar positioning in severe deep overbite, compared with the control group. Conclusion: There were significant changes in the TMJ components in severe deep overbite cases. Therefore, sever deep overbite could be considered a predisposing factor for temporomandibular disorders. [ABSTRACT FROM AUTHOR]

[Display omitted] • This is the most systematic review of flavonoid drugs and clinical candidates to date. • 19 flavonoid drugs are approved for the market, while 36 candidates in clinical phases. • 52.6% of the marketed flavonoid drugs and 44.4% of clinical candidates are natural sources. • 30% of the marketed flavonoid drugs are used for the treatment of cardiovascular diseases. • 50% of the suspended clinical candidates are antineoplastic and immunomodulating agents. • Unexpectedly, flavonoid glycosides account for 36.8% of the marketed flavonoid drugs. Flavonoids are one of the most important metabolites with vast structural diversity and a plethora of potential pharmacological applications, which have drawn considerable attention in the laboratory. Nevertheless, it remains uncertain how many candidates were progressed to clinical application. We carried out a critical review of natural and semi-synthetic flavonoid drugs and candidates undergoing different clinical phases worldwide by applying an adequate search method and conducted a brief cheminformatic and bioinformatic analysis. It was expected that the obtained results might narrow the screening scope and reduce the cost of drug research and development. To our knowledge, this is the most systematic summarization of flavonoid-based drugs and clinical candidates to date. It was found that a total of 19 flavonoid-based drugs have been approved for the market, and of these, natural flavonoids accounted for 52.6%. Besides, a total of 36 flavonoid-based clinical candidates are undergoing or suspended in different phases, and of these, natural flavonoids account for 44.4%. Thus, natural flavonoids remain the best option for finding novel agents/active templates, and when investigated in conjunction with synthetic chemicals and biologicals, they offer the potential to discover novel structures that can lead to effective agents against a variety of human diseases. Additionally, flavonoid-based marketed drugs have been successful in cardiovascular treatment, and the related drugs account for more than 30% of marketed drugs. However, the use of flavonoids as antineoplastic and immunomodulating agents is not likely for approximately 50% of the candidates suspended in the clinical stage. Interestingly, the marketed drugs covered a broader range of chemical spaces based on size, polarity, and three-dimensional structure compared to the clinical candidates. In addition, flavonoid glycosides with poor oral bioavailability account for 36.8% of the marketed drugs, and thus, they could be thoroughly investigated. [ABSTRACT FROM AUTHOR]

[Display omitted] • P450Rdb compiles a comprehensive catalog of over 1,600 reactions catalyzed by P450s. • P450Rdb has collected a diverse collection of more than 590 P450s from over 200 species. • P450Rdb systematically organizes all reactions based on their chemical reaction type and site. • P450Rdb provides a user-friendly interface on P450s and their associated reactions. • P450Rdb is beneficial for research in synthetic biology, pharmacology, and the chemical industry. Cytochrome P450 enzymes (P450s) are recognized as the most versatile catalysts worldwide, playing vital roles in numerous biological metabolism and biosynthesis processes across all kingdoms of life. Despite the vast number of P450 genes available in databases (over 300,000), only a small fraction of them (less than 0.2 %) have undergone functional characterization. To provide a convenient platform with abundant information on P450s and their corresponding reactions, we introduce the P450Rdb database, a manually curated resource compiles literature-supported reactions catalyzed by P450s. All the P450s and Reactions were manually curated from the literature and known databases. Subsequently, the P450 reactions organized and categorized according to their chemical reaction type and site. The website was developed using HTML and PHP languages, with the MySQL server utilized for data storage. The current version of P450Rdb catalogs over 1,600 reactions, involving more than 590 P450s across a diverse range of over 200 species. Additionally, it offers a user-friendly interface with comprehensive information, enabling easy querying, browsing, and analysis of P450s and their corresponding reactions. P450Rdb is free available at http://www.cellknowledge.com.cn/p450rdb/. We believe that this database will significantly promote structural and functional research on P450s, thereby fostering advancements in the fields of natural product synthesis, pharmaceutical engineering, biotechnological applications, agricultural and crop improvement, and the chemical industry. [ABSTRACT FROM AUTHOR]

Schematic illustration of CeCH for sepsis-induced myocardial injury. (A) Preparation of CeCH with self-assembled by HSA. (B) The mechanism of CeCH to show protective effect for sepsis-induced cardiac injury by inhibiting ferroptosis and inflammation. [Display omitted] • CeCH was successfully developed by a green self-assembled method with human serum albumin to increase the water solubility and poor bioavailability of curcumin. • CeCH performed SOD-like and CAT-like activities to eliminate ROS generation and inhibit ferroptosis in H9C2 cells. • CeCH reduced the secretion of inflammatory factors by M1 macrophages to suppress the inflammation. • CeCH protected the heart against sepsis-induced cardiac injury and reversed cardiac dysfunction in vivo. • A promising strategy with Cur and nanozyme for septic cardiomyopathy by inhibiting ferroptosis and inflammation in clinical application. Sepsis-induced cardiac injury is the leading cause of death in patients. Recent studies have reported that reactive oxygen species (ROS)-mediated ferroptosis and macrophage-induced inflammation are the two main key roles in the process of cardiac injury. The combination of ferroptosis and inflammation inhibition is a feasible strategy in the treatment of sepsis-induced cardiac injury. In the present study, ceria nanozyme coordination with curcumin (CeCH) was designed by a self-assembled method with human serum albumin (HSA) to inhibit ferroptosis and inflammation of sepsis-induced cardiac injury. The formed CeCH obtained the superoxide dismutase (SOD)-like and catalase (CAT)-like activities from ceria nanozyme to scavenge ROS, which showed a protective effect on cardiomyocytes in vitro. Furthermore, it also showed ferroptosis inhibition to reverse cell death from RSL3-induced cardiomyocytes, denoted from curcumin. Due to the combination therapy of ceria nanozyme and curcumin, the formed CeCH NPs could also promote M2 macrophage polarization to reduce inflammation in vitro. In the lipopolysaccharide (LPS)-induced sepsis model, the CeCH NPs could effectively inhibit ferroptosis, reverse inflammation, and reduce the release of pro-inflammatory factors, which markedly alleviated the myocardial injury and recover the cardiac function. Overall, the simple self-assembled strategy with ceria nanozyme and curcumin showed a promising clinical application for sepsis-induced cardiac injury by inhibiting ferroptosis and inflammation. [ABSTRACT FROM AUTHOR]

High-entropy alloys (HEAs) are newly developed materials that have many excellent properties, such as a high strength-to-weight ratio and excellent tensile properties. If high-entropy alloys and stainless steel are joined by welding, the advantages of their properties can be balanced. In this paper, dissimilar lap joining of Al 0.3 CoCrFeNi-HEA with 304 stainless steel was achieved using gas tungsten arc welding (GTAW) with different heat inputs. Macroscopic morphology, microstructure analysis and mechanical property tests of the welded joints were carried out. The results showed that the macroscopic morphology of the dissimilar welded joints is well-formed under different heat inputs. The penetration and width of the weld seam increased with the heat input, and the lap area of the welded joint also increased. There was the same microstructure in the weld seam with different heat inputs, including columnar dendrites near the fusion line and equiaxed dendrites at the weld centre. The ultimate shear strength of the welded joints increased from 442 MPa to 560 MPa with increasing heat input, and the elongation of the welded joints increased from 26 % to 41 %. With increasing heat input, the average microhardness of the weld zone (WZ) was approximately 145 HV. [ABSTRACT FROM AUTHOR]

Heatstroke (HS), associated with the early activation of the coagulation system and frequently presenting with thrombocytopenia, poses a significant healthcare challenge. Understanding the relationship of nadir platelet count (PLT) within 24 h for adverse outcomes in HS patients is crucial for optimizing management strategies. This retrospective cohort study, conducted in six tertiary care hospitals, involved patients diagnosed with HS and admitted to the emergency departments. The primary and secondary outcomes included in-hospital mortality and various acute complications, respectively, with logistic regression models utilized for assessing associations between nadir PLT and outcomes. The PLT count change curve was described using a generalized additive mixed model (GAMM), with additional analyses involving body temperature (BT) at 2 h also conducted. Of the 152 patients included, 19 (12.5%) died in-hospital. The median nadir PLT within 24 h was 99.5 (58.8–145.0)*10^9/L. Notably, as a continuous variable (10*10^9/L), nadir PLT was significantly associated with in-hospital mortality (OR 0.76; 95% CI 0.64–0.91; P = 0.003) and other adverse outcomes like acute kidney and liver injury, even after adjustment for confounders. GAMM revealed a more rapid and significant PLT decline in the non-survival group over 24 h, with differential PLT dynamics also observed based on BT at 2 h. Nadir PLT within 24 h were tied to in-hospital mortality and various adverse outcomes in HS patients. Early effective cooling measures demonstrated a positive impact on these associations, underscoring their importance in patient management. [ABSTRACT FROM AUTHOR]

To identify and quantify the factors associated with the reparability of rotator cuff tears (RCTs). PubMed, Scopus, and Web of Science databases were searched for clinical studies published in English focusing on RCT reparability by using the keywords "rotator cuff tear" and "reparability". A meta-analysis was conducted if ≥3 studies examined the same factor and provided enough data to assess RCT reparability. Quality assessment was completed using the quality assessment of diagnostic accuracy studies tool. Eighteen studies (2700 patients) were enrolled and 26 factors were included in the meta-analysis. The dichotomous variables associated with irreparability were Patte stage 3 (odds ratio (OR): 8.0, 95% confidence interval [CI]: 4.3-14.9), massive tear vs. large tear (OR: 3.1, 95% CI: 1.3-7.2), Goutallier stage for each tendon, and tangent sign (OR: 11.1, 95% CI: 4.3-28.4). The continuous variables associated with irreparability were age (mean difference (MD): 3.25, 95% CI: 1.4-5.1), mediolateral tear size (MD: 12.3, 95% CI: 5.8-18.9), anteroposterior tear size (MD: 10.4, 95% CI: 5.2-15.6), acromiohumeral distance on X-ray (MD: −2.3, 95% CI: −3.0 to −1.6) and magnetic resonance imaging (MD: −1.8, 95% CI: −2.8 to −0.9), and inferior glenohumeral distance on magnetic resonance imaging (MD: 2.2, 95% CI: 1.4-3.0). This study revealed that older age, larger tear size, severe fatty infiltration, muscle atrophy, and advanced superior migration of the humeral head were strongly associated with irreparable RCTs. Conversely, clinical symptoms provided limited information for predicting reparability. Additionally, the tangent sign emerged as a powerful and simple tool for individual prediction, and several quantitative scoring systems also proved useful. [ABSTRACT FROM AUTHOR]

Background and Objectives: Wheat gluten is a high‐quality, low‐priced, and nutritious plant protein. Applications of wheat gluten protein could be expanded by improving its solubility through enzymatic modifications. Herein, we investigated the effect of proteolytic processing on the physicochemical properties of wheat gluten protein. Findings: The degree of hydrolysis, trichloroacetic acid‐soluble nitrogen (TCA‐SN), and peptidyl nitrogen content of the enzymatic digestion products increased, and the TCA‐SN content exceeded 60% in all cases. The ζ‐potentials of all products after enzymatic digestion were significantly decreased and were negative. Three enzymatic solutions increased the stability of the solution system and the surface hydrophobicity of the enzymatic products to different degrees. The products after enzymatic digestion by alkaline protease had better antioxidant capacity. Conclusions: This study provides theoretical support for expanding the applications for wheat protein to achieve the added value of wheat products and enhance the utilization rate of these readily available raw materials. Significance and Novelty: This study investigates the dual enzyme stepwise enzymatic hydrolysis of wheat gluten protein by alkaline protease and neutral protease, which increases the water‐soluble protein content of wheat gluten protein. The resulting hydrolysate has a high peptide nitrogen content. [ABSTRACT FROM AUTHOR]

[Display omitted] Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated T H 2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. Real-time reverse transcription–quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5 -knockout mice were used to establish a nasal polyp model with T H 2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5 -deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions. [ABSTRACT FROM AUTHOR]

Recent research extends our knowledge of plasma lipid species, building on established links between serum lipid levels and Type 2 Diabetes Mellitus (T2DM) risk. Identifying the causal roles of these lipid species is key to improving T2DM risk assessment. This study employs Mendelian randomization (MR) to investigate the causal relationship between 179 lipid species across 13 lipid categories and T2DM. Summary-level data were sourced from genome-wide association studies. The primary analytical methods included the inverse variance weighted (IVW) approach and the Wald ratio, complemented by a series of sensitivity analyses to ensure the robustness of results. The IVW analysis reveals a significant causal association between elevated levels of ceramide (d40:2) (OR = 1.071, 95% CI 1.034–1.109, P = 1.36 × 10−4), sphingomyelin (d38:1) (OR = 1.052, 95% CI 1.028–1.077, P = 1.80 × 10−5), and triacylglycerol (56:8) (OR = 1.174, 95% CI 1.108–1.243, P = 4.65 × 10−8), and an increased risk of T2DM. Conversely, Wald ratio analysis indicates that higher levels of phosphatidylcholine (O-16:1_16:0) (OR = 0.928, 95% CI 0.892–0.966, P = 2.37 × 10−4), phosphatidylcholine (O-16:1_20:4) (OR = 0.932, 95% CI 0.897–0.967, P = 2.37 × 10−4), and phosphatidylcholine (O-18:2_20:4) (OR = 0.872, 95% CI 0.812–0.935, P = 1.24 × 10−4) are significantly associated with a reduced risk of T2DM. Furthermore, suggestive causal evidence for 22 additional lipid species was identified. This MR study establishes a causal relationship between specific lipid classes in modulating the risk of T2DM. It offers new insights for risk assessment and potential therapeutic targets in T2DM. • Mendelian Randomization study on 179 lipid species identifies key lipid types influencing T2DM risk. • Elevated levels of ceramide and sphingomyelin significantly increase T2DM risk; specific phosphatidylcholines lower it. • Results provide new insights for T2DM risk assessment, highlighting potential therapeutic targets. • Study uses genetic variants as instrumental variables to establish causal relationships between lipid types and T2DM. • Findings suggest that precise lipid profiling can refine T2DM risk stratification and guide interventions. [ABSTRACT FROM AUTHOR]

This article delves into the intricate challenge of implementing prescribed-time command filtered control in the context of uncertain nonlinear systems. Firstly, a prescribed-time function is defined to lay the groundwork for subsequent controller design. Subsequently, a novel prescribed-time command Filtered controller is proposed for high-order nonlinear systems featuring unknown parameters. This controller guarantees swift error convergence within a predefined time range, with the added capability of periodic error convergence to zero during subsequent controller operations. A pivotal innovation in this study lies in the controller's design, which remains unaffected by the system's initial conditions. This unique feature enables the prescribed time to be flexibly set within physical constraints, diverging markedly from conventional finite-time control theory. Theoretical analysis has conclusively shown that the controller achieves full-state tracking error convergence within the specified time frame. The efficacy of the research findings is substantiated through two simulation cases, underscoring a substantial contribution to the refinement and adaptability of nonlinear system control theory. • This article introduces a Prescribed Time Command Filtered Controller (PTCFC) for a specific class of uncertain high-order nonlinear systems with unknown parameters. • Through the design of a novel periodic finite-time function, the article achieves periodic asymptotic convergence of the control system tracking error. • The article proposes a novel compensation signal design scheme and combines it with a controller to achieve stability analysis of the control system and strict proof of periodic error convergence. [ABSTRACT FROM AUTHOR]

The hydrodynamic coefficient of an underwater manipulator varies with changes in posture and flow field, presenting significant challenges for precise control and localization. This study, conducted numerical simulations to investigate the patterns of variation in flow field and hydrodynamic coefficients. Results showed that hydrodynamic performance remained consistent when the posture of the manipulator was either axisymmetric or origin-symmetric. Upon rotation, axial flow extended across the entire downstream surface, and the Karman vortex street entirely eliminated. Pressure coefficients on the back pressure surface of the manipulator increased with the Reynolds number within the range of 6x10³ ≤ Re ≤ 3x104, while the pressure coefficient on the upstream surface remained unchanged. Within this range, drag coefficients for the upper and lower arms decreased by 27.4% and 23.9%, respectively. The hydrodynamic performance of the lower arm was independent of the upper arm's posture, with a maximum drag coefficient of 1.48 achieved at α = -90°. As the posture angle of the manipulator varied from 30° to 60°, the pressure coefficient on the upstream surface decreased from 0.75 to 0.25. [ABSTRACT FROM AUTHOR]