[Current clinical application of glomerular filtration rate assessment methods in pediatric populations]. / 肾小球滤过率评估方法在儿童人群中的应用现状.

Glomerular filtration rate (GFR) is a critical indicator of renal function assessment, which exhibits age-dependency in children and may differ from adults under various disease conditions. In recent years, there has been a growing focus on GFR among scholars, with an increasing number of clinical studies dedicated to refining and optimizing GFR estimation to span all pediatric age groups. However, the methods and assessment equations for estimating GFR may vary under different disease conditions, affecting the accuracy and applicability of assessments. This article reviews the peculiarities of renal function in children, explores GFR measurement methods, and evaluates the application of various GFR assessment equations in pediatric clinical practice, providing a reference for clinical assessment of renal function in children.

Benchmarking reverse docking through AlphaFold2 human proteome.

Predicting the binding of ligands to the human proteome via reverse-docking methods enables the understanding of ligand's interactions with potential protein targets in the human body, thereby facilitating drug repositioning and the evaluation of potential off-target effects or toxic side effects of drugs. In this study, we constructed 11 reverse docking pipelines by integrating site prediction tools (PointSite and SiteMap), docking programs (Glide and AutoDock Vina), and scoring functions (Glide, Autodock Vina, RTMScore, DeepRMSD, and OnionNet-SFCT), and then thoroughly benchmarked their predictive capabilities. The results show that the Glide_SFCT (PS) pipeline exhibited the best target prediction performance based on the atomic structure models in AlphaFold2 human proteome. It achieved a success rate of 27.8% when considering the top 100 ranked prediction. This pipeline effectively narrows the range of potential targets within the human proteome, laying a foundation for drug target prediction, off-target assessment, and toxicity prediction, ultimately boosting drug development. By facilitating these critical aspects of drug discovery and development, our work has the potential to ultimately accelerate the identification of new therapeutic agents and improve drug safety.

Composition Characterization of Crossostephium chinense Leaf Essential Oil and Its Anti-Inflammatory Activity Mechanisms.

This study investigates the composition characteristics and anti-inflammatory activity mechanisms of the essential oil from the leaves of Crossostephium chinense. C. chinense is a perennial herb commonly found in East Asia, traditionally used to treat various ailments. The essential oil extracted through water distillation, primarily contains 1,8-cineole (13.73%), santolina triene (13.53%), and germacrene D (10.67%). Three compounds were identified from the essential oil, namely 1-acetoxy-2-(2-hydroxypropyl)-5-methylhex-3,5-diene, 1-acetoxy-isopyliden-hex-5-en-4-one, and chrysanthemyl acetate, with the first two being newly discovered compounds. Then, the essential oil of C. chinense exhibits significant anti-inflammatory effects on RAW264.7 macrophages, effectively inhibiting the production of NO and ROS, with the IC50 value of 10.3 µg/mL. Furthermore, the essential oil reduces the expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß. Mechanistic studies indicate that the essential oil affects the inflammatory response by inhibiting the expression of iNOS but has no significant impact on COX-2. Further analysis suggests that the essential oil may regulate the inflammatory response through the ERK protein in the MAPK pathway and IκBα in the NF-κB pathway, while also promoting the activity of the NRF2/HO-1 antioxidant pathway, enhancing the cell's antioxidant capacity, thereby achieving an effect of inhibiting the inflammatory response. These results highlight the potential application value of C. chinense leaf essential oil in the medical and healthcare fields.

Mapping Spatial Strain Distribution and Its Effects on Optoelectronic Properties in Wrinkled Perovskite Films.

Organic-inorganic halide perovskite films, fabricated by using the antisolvent method, have garnered intense attention for their application in high-efficiency and stable solar cells. These films characteristically develop periodic wrinkled microstructures. Previous research has indicated that macroscopic residual strain significantly influences the optoelectronic behaviors of these films. However, the detailed interplay between the wrinkled morphology, strain distribution, and local photophysical properties at the micro- and nanoscale has not been fully elucidated. Here, we explore the microscopic morphology-strain-property relationship within wrinkled perovskite films employing correlative micro-optical and nanoelectrical microscopy techniques. Microphotoluminescence (PL) mapping supplemented by in situ strain PL measurements identifies a heterogeneous spatial strain distribution across the microstructural hills and valleys. Additionally, light-intensity-dependent photoconductive atomic force microscopy reveals that valleys experiencing less compressive strain exhibit a lower conductivity and a higher propensity for ion migration. The findings underscore the potential of targeted strain engineering to optimize the performance and longevity of perovskite solar cells.

In-situ nanozyme catalytic amplification coupled with a universal antibody orientation strategy based electrochemical immunosensor for AD-related biomarker.

An in-situ nanozyme signal tag combined with a DNA-mediated universal antibody-oriented strategy was proposed to establish a high-performance immunosensing platform for Alzheimer's disease (AD)-related biomarker detection. Briefly, a Zr-based metal-organic framework (MOF) with peroxidase (POD)-like activity was synthesized to encapsulating the electroactive molecule methylene blue (MB), and subsequently modified with a layer of gold nanoparticles on its surface. This led to the creation of double POD-like activity nanozymes surrounding the MB molecule to form a nanozyme signal tag. A large number of hydroxyl radicals were generated by the nanozyme signal tag with the help of H2O2, which catalyzed MB molecules in situ to achieve efficient signal amplification. Subsequently, a DNA-aptamer-mediated universal antibody-oriented strategy was proposed to enhance the binding efficiency for the antigen (target). Meanwhile, a poly adenine was incorporated at the end of the aptamer, facilitating binding to the gold electrode and providing anti-fouling properties due to the hydrophilicity of the phosphate group. Under optimal conditions, this platform was successfully employed for highly sensitive detection of AD-associated tau protein and BACE1, achieving limits of detection with concentrations of 3.34 fg/mL and 1.67 fg/mL, respectively. It is worth mentioning that in the tau immunosensing mode, 20 clinical samples from volunteers of varying ages were analyzed, revealing significantly higher tau expression levels in the blood samples of elderly volunteers compared to young volunteers. This suggests that the developed strategy holds great promise for early AD diagnosis.

Comparison of postoperative pain between InterTan and proximal femoral nail anti-rotation in femoral intertrochanteric fractures: a retrospective study.

OBJECTIVE: To compare the postoperative pain experienced by elderly patients with unstable trochanteric fractures treated with proximal femoral nail anti-rotation (PFNA) and InterTan Nail, focusing on identifying differences among this demographic. METHODS: A total of 40 elderly patients (age >80 years old) underwent treatment with either the PFNA Nail or InterTan Nail. Observational metrics included the Visual Analogue Scale (VAS) for pain, changes in implant position via X-ray, blood loss, fixation failures, and Harris Hip Scores (HHS) to assess complications and hip function at various time points. RESULTS: The study included 26 patients in the PFNA Nail group (Group A) and 26 patients in the InterTan Nail group (Group B). No significant differences were found in the main observational indicators between the two groups (all P>0.05). Both groups showed significant improvement in HHS post-surgery (all P<0.05). However, early post-operative pain scores were lower in the Group B (3.65±1.2) compared to Group A (5.5±0.9) (P<0.001). CONCLUSIONS: Despite different implant materials being used, outcomes in both groups were consistent and reliable among elderly patients. No significant differences were observed in terms of postoperative functional recovery, mortality, or complications between the groups. Notably, in the early postoperative period (3 days postoperatively), the Group B demonstrated significantly superior pain scores.

Three patients with new mutations in the EPCAM variant gene for congenital tufting enteropathy and a mutation review in China: a case report.

Background: Congenital tufting enteropathy (CTE) is a rare cause of intractable congenital diarrhea in children, always resulting in parenteral nutrition (PN) dependency. We aimed to report novel mutations in Chinese patients and to illustrate the clinical, histopathological, and molecular features of CTE in China. Case Description: We report three cases of CTE diagnosed with whole-exome sequencing (WES) and MOC31 [a monoclonal antibody of epithelial cell adhesion molecule (EPCAM)] immunohistochemistry. The main manifestations in the three patients were watery diarrhea and growth retardation. Upper endoscopy in three patients revealed villous atrophy of the duodenal mucosa. Histological examination revealed villus abnormalities and two patients with focal tufting. All of the three patients revealed a complete absence of EPCAM expression through MOC31 immunohistochemistry. Five novel mutations, including c.319delG, c.505_507delGAG, c.491+1G>C, c.60del (p.F20Lfs*17), and c.353G>A, in EPCAM were identified through molecular analysis. In our review, there were 18 different mutations in 11 patients from nine studies, with 12 mutations reported only once. In China, 73% of the patients were compound heterozygotes, and most of the pathogenic variants were in exon 3. All patients presented with congenital diarrhea and needed PN because of growth retardation, even when diarrhea was improved. Of the 11 patients, 3 (27%) died. Conclusions: CTE is rare and fatal, and lacks characteristic changes during endoscopy. Patients with CTE require early diagnosis via histological examination and genetic detection to improve survival.

Prognostic Hypoxia-Angiogenesis-Related Gene Signature in Hepatocellular Carcinoma, in Which HILPDA Contributes to Tumor Progression.

Objective: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer. Hypoxia can be involved in HCC tumor growth, invasion and metastasis through inducing angiogenesis. Nevertheless, the assessment of the impact of hypoxia and angiogenesis on the prognosis of HCC remains inadequate. Methods: According to hypoxia-angiogenesis-related genes (HARGs) expression information and clinical data from patients within the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort, we constructed a prognostic model (HARG-score) using bioinformatic tools. In addition to assessing the predictive ability of this prognostic model in both Liver Cancer-Riken-Japan (LIRI-JP) and GSE14520 cohorts, we analyzed the correlation between HARG-score and clinical characteristics, immune infiltration and immunotherapy efficacy. Moreover, we investigated the exact role and underlying mechanism of key HARGs through molecular experiments. Results: We constructed a 5-gene prognostic model HARG-score consisting of hypoxia-inducible lipid droplet-associated (HILPDA), erythropoietin (EPO), solute carrier family 2 member 1 (SLC2A1), proteasome subunit alpha type 7 (PSMA7) and cAMP responsive element-binding protein 1 (CREB1) through differentially expressed HARGs. The findings demonstrated that HARG-score was a good predictor of the prognosis of HCC patients from distinct cohorts and was correlated with clinical characteristics and immune infiltration. Furthermore, the HARG-score was identified as an independent prognostic factor. Lower HARG-score implied greater immunotherapy efficacy and better response. The expression and prognostic significance of these 5 genes were additionally validated in clinical data. In addition, experimental data revealed that the key gene HILPDA contributes to the progression of HCC through facilitating angiogenesis and affecting the expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Conclusion: HARG-score has promising applications in prognosis prediction of HCC patients, in which HILPDA may be a latent prognostic biomarker and therapeutic target, providing a foundation for further research and treatment of HCC.

Characterization of ultrasonic vibration and polishing force in sapphire ultrasonic vibration-assisted flexible polishing: Insights from in-situ monitoring systems.

Sapphire ultrasonic vibration-assisted flexible polishing (UVAFP) is a promising technique for comprehensively improving the surface integrity of machined parts. The technique was performed on an ultra-precision machine tool with the in-situ monitoring systems in this paper, which aims to provide a new perspective for understanding the material removal mechanisms in the sapphire UVAFP process. A Taguchi L9 (43) orthogonal experiment was conducted to investigate the effects of feed distance, spindle speed, ultrasonic vibration (UV), and polishing time on the surface finish and material removal in the process. In addition, the effect of a polyurethane ball tool is not trivial. A single-factor experiment was conducted for exploring it. Based on a laser displacement measurement system and an acoustic emission sensor system, the characteristics of time-dependent ultrasonic amplitude and ultrasonic frequency for the sapphire UVAFP system were analyzed, with the effectiveness of UV demonstrated. Based on a three-component force measurement system, the characteristics of normal force and its relationship with process parameters and tool deformation were analyzed, with macro- and micro-level examined. In conclusion, this paper presents the characterization of UV and polishing force in the sapphire UVAFP process, providing novel insights into understanding the material removal mechanisms of sapphire and even more manufacturing problems.

A Framework for Measuring Tree Rings Based on Panchromatic Images and Deep Learning.

Tree-ring data are pivotal for decoding the age and growth patterns of trees, reflecting the impact of environmental factors over time. Addressing the significant shortcomings of traditional, labour-intensive and resource-demanding methods, we propose an innovative automated technique that utilizes panchromatic images and deep learning for measuring tree rings. The method utilizes convolutional neural networks to enhance image quality, precisely delineate tree rings through segmentation and perform ring counting and width calculation in the post-processing stage. We compiled an extensive data set from diverse sources, including Beijing Forestry University and the Summer Palace, to train our algorithm. The performance of our method was validated empirically, demonstrating its potential to transform tree-ring analysis and provide deeper insights into ecological and climatological research.

Cholesterol suppresses AMFR-mediated PDL1 ubiquitination and degradation in HCC.

The degradation of proteasomes or lysosomes is emerging as a principal determinant of programmed death ligand 1 (PDL1) expression, which affects the efficacy of immunotherapy in various malignancies. Intracellular cholesterol plays a central role in maintaining the expression of membrane receptors; however, the specific effect of cholesterol on PDL1 expression in cancer cells remains poorly understood. Cholesterol starvation and stimulation were used to modulate the cellular cholesterol levels. Immunohistochemistry and western blotting were used to analyze the protein levels in the samples and cells. Quantitative real-time PCR, co-immunoprecipitation, and confocal co-localization assays were used for mechanistic investigation. A xenograft tumor model was constructed to verify these results in vivo. Our results showed that cholesterol suppressed the ubiquitination and degradation of PDL1 in hepatocellular carcinoma (HCC) cells. Further mechanistic studies revealed that the autocrine motility factor receptor (AMFR) is an E3 ligase that mediated the ubiquitination and degradation of PDL1, which was regulated by the cholesterol/p38 mitogenic activated protein kinase axis. Moreover, lowering cholesterol levels using statins improved the efficacy of programmed death 1 (PD1) inhibition in vivo. Our findings indicate that cholesterol serves as a signal to inhibit AMFR-mediated ubiquitination and degradation of PDL1 and suggest that lowering cholesterol by statins may be a promising combination strategy to improve the efficiency of PD1 inhibition in HCC.

Physics-Informed Inverse Design of Programmable Metasurfaces.

Emerging reconfigurable metasurfaces offer various possibilities for programmatically manipulating electromagnetic waves across spatial, spectral, and temporal domains, showcasing great potential for enhancing terahertz applications. However, they are hindered by limited tunability, particularly evident in relatively small phase tuning over 270°, due to the design constraints with time-intensive forward design methodologies. Here, a multi-bit programmable metasurface is demonstrated capable of terahertz beam steering facilitated by a developed physics-informed inverse design (PIID) approach. Through integrating a modified coupled mode theory (MCMT) into residual neural networks, the PIID algorithm not only significantly increases the design accuracy compared to conventional neural networks but also elucidates the intricate physical relations between the geometry and the modes. Without decreasing the reflection intensity, the method achieves the enhanced phase tuning as large as 300°. Additionally, the inverse-designed programmable beam steering metasurface is experimentally validated, which is adaptable across 1-bit, 2-bit, and tri-state coding schemes, yielding a deflection angle up to 68° and broadened steering coverage. The demonstration provides a promising pathway for rapidly exploring advanced metasurface devices, with potentially great impact on communication and imaging technologies.

Transcranial direct current stimulation and neuronal functional connectivity in MCI: role of individual factors associated to AD.

Background: Alzheimer's disease (AD) encompasses a spectrum that may progress from mild cognitive impairment (MCI) to full dementia, characterized by amyloid-beta and tau accumulation. Transcranial direct current stimulation (tDCS) is being investigated as a therapeutic option, but its efficacy in relation to individual genetic and biological risk factors remains underexplored. Objective: To evaluate the effects of a two-week anodal tDCS regimen on the left dorsolateral prefrontal cortex, focusing on functional connectivity changes in neural networks in MCI patients resulting from various possible underlying disorders, considering individual factors associated to AD such as amyloid-beta deposition, APOE ϵ4 allele, BDNF Val66Met polymorphism, and sex. Methods: In a single-arm prospective study, 63 patients with MCI, including both amyloid-PET positive and negative cases, received 10 sessions of tDCS. We assessed intra- and inter-network functional connectivity (FC) using fMRI and analyzed interactions between tDCS effects and individual factors associated to AD. Results: tDCS significantly enhanced intra-network FC within the Salience Network (SN) and inter-network FC between the Central Executive Network and SN, predominantly in APOE ϵ4 carriers. We also observed significant sex*tDCS interactions that benefited inter-network FC among females. Furthermore, the effects of multiple modifiers, particularly the interaction of the BDNF Val66Met polymorphism and sex, were evident, as demonstrated by increased intra-network FC of the SN in female Met non-carriers. Lastly, the effects of tDCS on FC did not differ between the group of 26 MCI patients with cerebral amyloid-beta deposition detected by flutemetamol PET and the group of 37 MCI patients without cerebral amyloid-beta deposition. Conclusions: The study highlights the importance of precision medicine in tDCS applications for MCI, suggesting that individual genetic and biological profiles significantly influence therapeutic outcomes. Tailoring interventions based on these profiles may optimize treatment efficacy in early stages of AD.

Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcγRIIb binding.

Allergen-crosslinked IgE triggers allergy by interacting with its receptor on basophils and mast cells. The anti-IgE monoclonal antibody omalizumab can alleviate allergy by competing with the receptor for IgE binding. However, along with neutralization, omalizumab also inhibits IgE degradation, which is clinically associated with high dose and total IgE accumulation problems. In this study, we have developed an IgE-eliminating antibody on the basis of omalizumab, which has pH-dependent Fabs and an Fc with high affinity for FcγRIIb. In mice, the antibody rapidly eliminated total serum IgE to baseline levels and caused lower free IgE levels than omalizumab. At low dosages, the antibody also exhibited favorable IgE elimination effects. In addition, the antibody can degrade the corresponding allergen with the removal of IgE, addressing the allergy from its source. Introduction of the M252Y/S254T/T256E (YTE) mutation into this antibody prolongs its serum half-life without reducing potency. Thus, this engineered antibody holds a promising therapeutic option for allergy patients. Mechanistic insights are also included in this study.

Dementia Incidence in Survivors of Multiple Myeloma: A National Case-Control Study Conducted in Korea (The CAREMM-2106 Study).

BACKGROUND: Dementia, a growing global health issue, affects older adults and specific groups like long-term cancer survivors. The link between cancer survival and dementia is debated. Multiple myeloma (MM), a common blood cancer in older adults, is often linked with cognitive issues. This study investigated dementia incidence in long-term MM survivors using Korean national data. METHODS: A retrospective case-control study used data from the Korea National Health Insurance Service (KNHIS), covering about 50 million Koreans. Patients diagnosed with MM between 2009 and 2020 formed the case cohort, while the control cohort included matched individuals without MM using propensity-score matching. Analyzing baseline characteristics, comorbidities, and socioeconomic status, the primary outcome was dementia incidence identified via ICD-10 codes. Statistical methods included Kaplan-Meier plots, cause-specific and Fine-Gray subdistribution hazard models, and a 3-year landmark analysis for immortal time bias. RESULTS: The study included 33,864 patients, with 16,932 in each cohort. The overall cumulative dementia incidence was lower in the MM cohort compared to controls. However, in the first 3 years, MM patients had a higher dementia risk (HR: 1.711, 95% CI, 1.562-1.874) than controls. After 3 years, the risk significantly decreased (HR: 0.625, 95% CI, 0.560-0.696). Age-specific analysis showed a consistent pattern, particularly among MM patients aged 70-79, where dementia risk increased post-3 years. CONCLUSION: This study reveals a lower long-term dementia risk in MM survivors compared to non-MM individuals. Further prospective studies are needed to confirm these findings and explore the underlying mechanisms.

A cross-sectional study on predictors of patients' tinnitus severity.

Objective: To identify factors that influence the severity of tinnitus via a hierarchical multiple linear regression model. Methods: The study was a retrospective cross-sectional analysis. The study included 331 patients experiencing tinnitus as their primary concern, who visited Shanghai Changzheng Hospital of the Navy Medical University between 2019 and 2021. Data on general health status and disease characteristics were collected from all patients. With their consent, participants underwent audiological evaluatons and completed questionnaires to analyze the characteristics of their tinnitus and the factors influencing its severity. Results: The correlation analysis showed a positive relationship between tinnitus frequency, tinnitus loudness, SAS scores, and PSQI scores with THI scores (P < 0.05) among nine examined variables (gender, handedness, employment status, age, BMI, tinnitus frequency, tinnitus loudness, SAS scores, and PSQI scores). The variables that were extracted from the multiple regression were; for the constant; ß = -51.797, t = -4.484, P < 0.001, variable is significant; for the tinnitus loudness; ß = 0.161, t = 2.604, P < 0.05, variable is significant; for the tinnitus frequency; ß = 0.000, t = 1.269, P = 0.206, variable is not significant; for the SAS scores; ß = 1.310, t = 7.685, P < 0.001, variable is significant; for the PSQI scores; ß = 1.680, t = 5.433, P < 0.001, variable is significant. Therefore, the most accurate model for predicting severity in tinnitus patients is a linear combination of the constant, tinnitus loudness, SAS scores, and PSQI scores, Y(Tinnitus severity) = ß 0 + ß 1 (Tinnitus loudness) + ß 2 (SAS scores) + ß 3 (PSQI scores). ß 0, ß 1, ß 2, and ß 3 are -51.797, 0.161, 1.310 and 1.680, respectively. Conclusion: Tinnitus severity is positively associated with loudness, anxiety levels, and sleep quality. To effectively manage tinnitus in patients, it is essential to promptly identify and address these accompanying factors and related symptoms.

A novel hybrid optimization model for evaluating and forecasting air quality grades.

Air pollution has a significant global impact on natural resources and public health. Accurate prediction of air pollution is crucial for effective prevention and control measures. However, due to regional variations, different cities may have varying primary pollutants, posing new challenges for accurate prediction. In this paper, we propose a novel method called FP-RF, which integrates clustering algorithms to categorize multiple cities according to their air quality index values. Subsequently, we apply functional principal component analysis to extract the primary components of air pollution within each cluster. Furthermore, an enhanced random forest algorithm is utilized to predict air quality grades for each city. We conduct experimental evaluations using authentic historical data from Anhui Province spanning from 2018 to 2023. The results unequivocally establish the effectiveness of our model, with an average accuracy rate of 98.6% in forecasting six pollution grades and 96.04% accuracy in predicting 16 prefecture-level cities, surpassing performance compared to other baseline models.

Structural basis of psychedelic LSD recognition at dopamine D1 receptor.

Understanding the kinetics of LSD in receptors and subsequent induced signaling is crucial for comprehending both the psychoactive and therapeutic effects of LSD. Despite extensive research on LSD's interactions with serotonin 2A and 2B receptors, its behavior on other targets, including dopamine receptors, has remained elusive. Here, we present cryo-EM structures of LSD/PF6142-bound dopamine D1 receptor (DRD1)-legobody complexes, accompanied by a ß-arrestin-mimicking nanobody, NBA3, shedding light on the determinants of G protein coupling versus ß-arrestin coupling. Structural analysis unveils a distinctive binding mode of LSD in DRD1, particularly with the ergoline moiety oriented toward TM4. Kinetic investigations uncover an exceptionally rapid dissociation rate of LSD in DRD1, attributed to the flexibility of extracellular loop 2 (ECL2). Moreover, G protein can stabilize ECL2 conformation, leading to a significant slowdown in ligand's dissociation rate. These findings establish a solid foundation for further exploration of G protein-coupled receptor (GPCR) dynamics and their relevance to signal transduction.