Preoperative Prediction of Axillary Lymph Node Metastasis in Patients With Breast Cancer Through Multimodal Deep Learning Based on Ultrasound and Magnetic Resonance Imaging Images.

RATIONALE AND OBJECTIVES: Deep learning can enhance the performance of multimodal image analysis, which is known for its noninvasive attributes and complementary efficacy, in predicting axillary lymph node (ALN) metastasis. Therefore, we established a multimodal deep learning model incorporating ultrasound (US) and magnetic resonance imaging (MRI) images to predict ALN metastasis in patients with breast cancer. MATERIALS AND METHODS: A retrospective cohort of patients with histologically confirmed breast cancer from two hospitals composed of the primary cohort (n = 465) and the external validation cohort (n = 123). All patients had undergone both preoperative US and MRI scans. After data preprocessing, three convolutional neural network models were used to analyze the US and MRI images, respectively. After integrating the US and MRI deep learning prediction results (DLUS and DLMRI, respectively), a multimodal deep learning (DLMRI+US+Clinical parameter) model was constructed. The predictive ability of the proposed model was compared to that of the DLUS, DLMRI, combined bimodal (DLMRI+US), and clinical parameter models. Evaluation was performed using the area under the receiver operating characteristic curves (AUCs) and decision curves. RESULTS: A total of 588 patients with breast cancer participated in this study. The DLMRI+US+Clinical parameter model outperformed the alternative models, achieving the highest AUCs of 0.819 (95% confidence interval [CI] 0.734-0.903) and 0.809 (95% CI 0.723-0.895) on the internal and external validation sets, respectively. The decision curve analysis confirmed its clinical usefulness. CONCLUSION: The DLMRI+US＋Clinical parameter model demonstrates the feasibility and reliability of its performance for ALN metastasis prediction in patients with breast cancer.

A simple numerical simulation model can elucidate the key factors for designing a miniaturized ion trap mass spectrometer.

BACKGROUND: Miniature ion trap mass spectrometer enables mass-to-charge ratio analysis of ions via quadrupole field in a low vacuum environment. It plays an important role in on-site detection due to its portability and specificity. In order to gain a deeper understanding of the analysis mechanism of miniature ion trap mass spectrometers, a quadrupole MS ion trajectory numerical simulation model (QITNS) is established in this paper for ions trajectory calculation under the action of quadrupole field, exciting field and neutral gas molecule collision. Compared with the existing methods, the model in this paper is simpler and more direct, which effectively explored the effects of dipole excitation and quadrupole excitation on ion manipulation under high background pressure. RESULTS: The simulation results demonstrate that high RF amplitude, low auxiliary AC amplitude and quadrupole excitation can effectively improve the isolation resolution. Besides, it clarified the difference between the analysis mechanism of ion trap mass spectrometers under high background pressure (above 13.332 Pa) and absolute vacuum conditions. The relevant results are consistent with the conclusions of previous experiments and other theories, proving the applicability and accuracy of the proposed calculation model and solution method. SIGNIFICANCE: This research bears the guiding significance for further understanding the mechanism of quadrupole mass spectrometry as well as designing and developing miniature mass spectrometers.

DECODE: Contamination-Free Digital CRISPR Platform for Point-of-Care Detection of Viral DNA/RNA.

Rapid and precise nucleic acid testing at the point-of-care (POC) is essential for effective screening and management of infectious diseases. Current polymerase-based molecular diagnostics often suffer from potential cross-contamination issues, particularly in POC settings. Here, we introduce DECODE, a contamination-free nucleic acid detection platform integrating digital microfluidics (DMF) for nucleic acid extraction and a digital CRISPR amplification-free assay for pathogen detection. The digital CRISPR assay demonstrates sensitivity, detecting target DNA and RNA in the reaction mixture at concentrations of 10 and 5 copies/µL, respectively. Leveraging DMF-extracted samples enhances the performance of the digital CRISPR amplification-free assay. DECODE offers a sample-to-result workflow of 75 min using compact devices. Validation studies using clinical samples confirm DECODE's robust performance, achieving 100% sensitivity and specificity in detecting HPV18 from cervical epithelial cells and influenza A from nasal swabs. DECODE represents a versatile, contamination-free detection platform poised to enhance integrated public health surveillance efforts.

Exogenous iron caused osteocyte apoptosis, increased RANKL production, and stimulated bone resorption through oxidative stress in a murine model.

Iron overload is a risk factor for osteoporosis due to its oxidative toxicity. Previous studies have demonstrated that an excessive amount of iron increases osteocyte apoptosis and receptor activator of nuclear factor κ-B ligand (RANKL) production, which stimulates osteoclast differentiation in vitro. However, the effects of exogenous iron supplementation-induced iron overload on osteocytes in vivo and its role in iron overload-induced bone loss are unknown. This work aimed to develop an iron overloaded murine model of C57BL/6 mice by intraperitoneal administration of iron dextran for two months. The iron levels in various organs, bone, and serum, as well as the microstructure and strength of bone, apoptosis of osteocytes, oxidative stress in bone tissue, and bone formation and resorption, were assessed. The results showed that 2 months of exogenous iron supplementation significantly increased iron levels in the liver, spleen, kidney, bone tissue, and serum. Iron overload negatively affected bone microstructure and strength. Osteocyte apoptosis and empty lacunae rate were elevated by exogenous iron. Iron overload upregulated RANKL expression but had no significant impact on osteoprotegerin (OPG) and sclerostin levels. Static and dynamic histologic analyses and serum biochemical assay showed that iron overload increased bone resorption without significantly affecting bone formation. Exogenous iron promoted oxidative stress in osteocytes in vivo and in vitro. Additional supplementation of iron chelator (deferoxamine) or N-acetyl-l-cysteine (NAC) partially alleviated bone loss, osteocyte apoptosis, osteoclast formation, and oxidative stress due to iron overload. These findings, in line with prior in vitro studies, suggest that exogenous iron supplementation induces osteoclastogenesis and osteoporosis by promoting osteocyte apoptosis and RANKL production via oxidative stress.

Barbed arrow-like structure membrane with ultra-high rectification coefficient enables ultra-fast, highly-sensitive lateral-flow assay of cTnI.

Acute myocardial infarction (AMI) has become a public health disease threatening public life safety due to its high mortality. The lateral-flow assay (LFA) of a typical cardiac biomarker, troponin I (cTnI), is essential for the timely warnings of AMI. However, it is a challenge to achieve an ultra-fast and highly-sensitive assay for cTnI (hs-cTnI) using current LFA, due to the limited performance of chromatographic membranes. Here, we propose a barbed arrow-like structure membrane (BAS Mem), which enables the unidirectional, fast flow and low-residual of liquid. The liquid is rectified through the forces generated by the sidewalls of the barbed arrow-like grooves. The rectification coefficient of liquid flow on BAS Mem is 14.5 (highest to date). Using BAS Mem to replace the conventional chromatographic membrane, we prepare batches of lateral-flow strips and achieve LFA of cTnI within 240 s, with a limit of detection of 1.97 ng mL-1. The lateral-flow strips exhibit a specificity of 100%, a sensitivity of 93.3% in detecting 25 samples of suspected AMI patients. The lateral-flow strips show great performance in providing reliable results for clinical diagnosis, with the potential to provide early warnings for AMI.

The Role of TRAIL Signaling in Cancer: Searching for New Therapeutic Strategies.

Cancer continues to pose a significant threat to global health, with its status as a leading cause of death remaining unchallenged. Within the realm of cancer research, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) stands out as a critical player, having been identified in the 1990s as the tenth member of the TNF family. This review examines the pivotal role of TRAIL in cancer biology, focusing on its ability to induce apoptosis in malignant cells through both endogenous and exogenous pathways. We provide an in-depth analysis of TRAIL's intracellular signaling and intercellular communication, underscoring its potential as a selective anticancer agent. Additionally, the review explores TRAIL's capacity to reshape the tumor microenvironment, thereby influencing cancer progression and response to therapy. With an eye towards future developments, we discuss the prospects of harnessing TRAIL's capabilities for the creation of tailored, precision-based cancer treatments, aiming to enhance efficacy and improve patient survival rates.

The Emerging Role of Ferroptosis in EBV-Associated Cancer: Implications for Cancer Therapy.

Ferroptosis is a novel and iron-dependent form of programmed cell death, which has been implicated in the pathogenesis of various human cancers. EBV is a well-recognized oncogenic virus that controls multiple signaling pathways within the host cell, including ferroptosis signaling. Recent studies show that inducing ferroptosis could be an efficient therapeutic strategy for EBV-associated tumors. This review will firstly describe the mechanism of ferroptosis, then summarize EBV infection and EBV-associated tumors, as well as the crosstalk between EBV infection and the ferroptosis signaling pathway, and finally discuss the role and potential application of ferroptosis-related reagents in EBV-associated tumors.

Dual-Mode Fluorescent/Intelligent Lateral Flow Immunoassay Based on Machine Learning Algorithm for Ultrasensitive Analysis of Chloroacetamide Herbicides.

Given the harmful effect of pesticide residues, it is essential to develop portable and accurate biosensors for the analysis of pesticides in agricultural products. In this paper, we demonstrated a dual-mode fluorescent/intelligent (DM-f/DM-i) lateral flow immunoassay (LFIA) for chloroacetamide herbicides, which utilized horseradish peroxidase-IgG conjugated time-resolved fluorescent nanoparticle probes as both a signal label and amplification tool. With the newly developed LFIA in the DM-f mode, the limits of detection (LODs) were 0.08 ng/mL of acetochlor, 0.29 ng/mL of metolachlor, 0.51 ng/mL of Propisochlor, and 0.13 ng/mL of their mixture. In the DM-i mode, machine learning (ML) algorithms were used for image segmentation, feature extraction, and correlation analysis to obtain multivariate fitted equations, which had high reliability in the regression model with R2 of 0.95 in the range of 2 × 102-2 × 105 pg/mL. Importantly, the practical applicability was successfully validated by determining chloroacetamide herbicides in the corn sample with good recovery rates (85.4 to 109.3%) that correlate well with the regression model. The newly developed dual-mode LFIA with reduced detection time (12 min) holds great potential for pesticide monitoring in equipment-limited environments using a portable test strip reader and laboratory conditions using ML algorithms.

Finite element analysis of a novel anatomical plate in posterolateral plateau fractures.

Objective: This study aims to analyze the biomechanical characteristics of posterolateral plateau fractures fixed by a novel anatomical plate using finite element analysis. Methods: A three-dimensional digital model of the full length of right tibiofibula was obtained by CT scanning. A posterolateral tibial plateau fracture model was then created. The acquired fracture model was assembled with 4 groups of internal fixations: Group A, novel anatomical plate; Group B, straight buttress plate; Group C, oblique T-shaped locking plate; Group D, two lag screws. Axial loads of 500, 1,000 and 1,500 N perpendicular to the horizontal plane were used to simulate the stress on the lateral plateau of a 65 kg person standing, walking and fast running. Results: Vertical displacements of the posterolateral fragments in each of the four groups gradually increased under loads from 500 N to 1,500 N. The maximum displacement of the fracture fragment in four groups were all located on the lateral side of the proximal part, and the displacement gradually decreased from the proximal part to the distal end. The maximum displacement values under the axial load of 1,500 N was in the following order: novel anatomical plate (1.2365 mm) < oblique T-shaped locking plate (1.314 mm) < two lag screws (1.3747 mm) < straight buttress plate (1.3932 mm). As the axial load increased, the stress value of the different internal fixation models gradually increased. The stress behavior of the same internal fixation model under different loads was similar. The maximum stress value under the axial load of 1,500 N was in the following order: novel anatomical plate (114.63 MPa) < oblique T-shaped locking plate (277.17 MPa) < two lag screws (236.75 MPa) < straight buttress plate (136.2 MPa). Conclusion: The patients with posterolateral plateau fractures fixed with a novel anatomical plate in standing, walking and fast running can achieve satisfactory biomechanical results, which lays the foundation for future applications. At the same time, clinical fracture types are often diverse and accompanied by damage to the soft tissue. Therefore, the ideal surgical approach and appropriate internal fixation must be selected based on the patient's injury condition.

Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study.

BACKGROUND: Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. METHODS: In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. RESULTS: The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). CONCLUSIONS: This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

Maternal Depressive Symptoms and Offspring Internalizing Problems: A Cross-Lagged Panel Network Analysis in Late Childhood and Early Adolescence.

The present study investigated the relations between maternal depressive symptoms and internalizing problems in offspring during late childhood and early adolescence, examining sex differences using symptom network analysis. A total of 885 Chinese youths in late childhood (n = 497, 38.6% girls; age = 9.58 years, SD = 0.24) and early adolescence (n = 388, 48.5% girls; age = 11.30 years, SD = 0.24) and their mothers (Mage = 37.34 years, SD = 5.42) were recruited. Cross-lagged panel network (CLPN) analysis was used to explore bridge symptoms (i.e., symptoms connecting two or more mental disorders) and identify transmission pathways between maternal depressive symptoms and offspring's internalizing problems at these two developmental stages. The CLPN results revealed that in late childhood, the bridge connections in the network model were boys feeling worried to mothers feeling distractible, and girls feeling worried to mothers feeling powerless. In early adolescence, the bridge connections were boys experiencing depressed mood to mothers feeling powerless, and mothers feeling bad to girls experiencing depressed mood. These findings highlight the network-level relations between maternal depressive symptoms and offspring internalizing problems. They provide insights into the developmental differences and similarities in symptoms during these periods and suggest ways to break the vicious cycle of psychopathology between mothers and their children.

Radiomics-Based Machine Learning Classification Strategy for Characterization of Hepatocellular Carcinoma on Contrast-Enhanced Ultrasound in High-Risk Patients with LI-RADS Category M Nodules.

Objective Accurate differentiation within the LI-RADS category M (LR-M) between hepatocellular carcinoma (HCC) and non-HCC malignancies (mainly intrahepatic cholangiocarcinoma [CCA] and combined hepatocellular and cholangiocarcinoma [cHCC-CCA]) is an area of active investigation. We aimed to use radiomics-based machine learning classification strategy for differentiating HCC from CCA and cHCC-CCA on contrast-enhanced ultrasound (CEUS) images in high-risk patients with LR-M nodules. Methods A total of 159 high-risk patients with LR-M nodules (69 HCC and 90 CCA/cHCC-CCA) who underwent CEUS within 1 month before pathologic confirmation from January 2006 to December 2019 were retrospectively included (111 patients for training set and 48 for test set). The training set was used to build models, while the test set was used to compare models. For each observation, six CEUS images captured at predetermined time points (T1, peak enhancement after contrast injection; T2, 30 seconds; T3, 45 seconds; T4, 60 seconds; T5, 1-2 minutes; and T6, 2-3 minutes) were collected for tumor segmentation and selection of radiomics features, which included seven types of features: first-order statistics, shape (2D), gray-level co-occurrence matrix, gray-level size zone matrix, gray-level run length matrix, neighboring gray tone difference matrix, and gray-level dependence matrix. Clinical data and key radiomics features were employed to develop the clinical model, radiomics signature (RS), and combined RS-clinical (RS-C) model. The RS and RS-C model were built using the machine learning framework. The diagnostic performance of these three models was calculated and compared. Results Alpha-fetoprotein (AFP), CA19-9, enhancement pattern, and time of washout were included as independent factors for clinical model (all p < 0.05). Both the RS and RS-C model performed better than the clinical model in the test set (area under the curve [AUC] of 0.698 [0.571-0.812] for clinical model, 0.903 [0.830-0.970] for RS, and 0.912 [0.838-0.977] for the RS-C model; both p < 0.05). Conclusions Radiomics-based machine learning classifiers may be competent for differentiating HCC from CCA and cHCC-CCA in high-risk patients with LR-M nodules.

Complete dislodgement of a mechanical valve prosthesis: A rare but potentially life-threatening event: a case report.

RATIONALE: Complete dislodgement of a mechanical valve is extremely uncommon as a long-term issue after getting a substitute mitral valve, and this report details an incident of complete detachment of a mechanical valve. PATIENT CONCERNS: A 50-year-old woman, who underwent mitral mechanical valve replacement 2 decades earlier at another facility, was urgently admitted due to sudden cardiogenic shock. DIAGNOSES: Transthoracic echocardiograms revealed severe malfunction of the mitral valve prosthesis, characterized by significant mitral regurgitation and moderate pulmonary hypertension. Following the insertion of extracorporeal membrane oxygenation and an intra-aortic balloon pump, the hemodynamics stabilized. Coronary angiography displayed the prosthetic mitral valve ring and leaflet floating in the left atrium, as confirmed by preoperative real-time 3-dimensional transesophageal echocardiography. A complete separation of the prosthetic ring and leaflet from the suture ring was observed. INTERVENTIONS: The patient promptly underwent bioprosthetic mitral valve replacement. OUTCOMES: The patient's postoperative course was uneventful, leading to discharge in good condition. LESSONS: A crucial aspect is comprehending the structure of the prosthetic valve itself. The use of transthoracic echocardiography and real-time 3-dimensional transesophageal echocardiography provides additional structural and functional details, enhancing support for potential life-saving interventions. Echocardiography plays a significant role in evaluating the morphology and function of prosthetic valves.

Rapid Separation and Detection of Drugs in Complex Biological Matrix Using TD-CDI Mass Spectrometer.

The drug detection technology plays a pivotal role in the domains of pharmaceutical regulation and law enforcement. In this study, we introduce a method that combines thermal desorption corona discharge ionization (TD-CDI) with mass spectrometry for efficient drug detection. The TD-CDI module, characterized by its compact and simple design, enables the separation of analytes within seconds and real-time presentation of one or two analyte peaks on the mass spectrum most of the time, which reduces matrix interference and improves detection performance. Through experimental investigation, we studied the characteristics of TD-CDI for analyte separation and detection, even with the same mass number, and optimized the TD-CDI approach. TD-CDI-MS was employed for the rapid detection of drugs in various traditional medicine, food products, and human samples. Additionally, by utilizing TD-CDI for segmented hair direct analysis, it becomes possible to trace the drug usage cycle of individuals. This underscores the feasibility of the proposed analytical method within the realm of drug detection.

Early onset stage III diabetic nephropathy in a child with Prader-Willi syndrome treated with dulaglutide: a case report.

Background: Prader-Willi syndrome (PWS) is a multisystem genetic disorder caused by chromosomal imprinting gene defects, with approximately 70% of cases resulting from paternal deletion of the chromosomal region 15. The main clinical features include severe infantile hypotonia, early-onset childhood obesity, hyperphagia, and underdeveloped external genitalia. As individuals with PWS age, they may exhibit irritability, social dysfunction, impaired gonadal development, and metabolic syndrome. Previous literature places the prevalence of type 2 diabetes mellitus (T2DM) in PWS at approximately 7-24%. Oxytocin is a neuropeptide secreted by the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus and regulates energy metabolism, which is involved in PWS. Due to age limitations, very few patients progress to diabetic nephropathy during childhood, and reports of typical diabetic nephropathy in PWS during childhood are extremely rare. Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist which can be used in the treatment of T2DM. Case Description: This article reports a case of a child with PWS complicated by stage III diabetic nephropathy, providing a retrospective analysis of the diagnosis and treatment process, as well as a review of domestic and international literature, to enhance understanding of this condition. And this article provides a treatment idea for PWS patients with diabetic nephropathy. Conclusions: It is very important to enhance understanding of PWS. And we offer new diagnostic and possible therapeutic approaches for pediatric patients with diabetic nephropathy.

Carbon dioxide radical anion mediated dehalogenation kinetics and mechanisms of halogenated alkanes.

Carbon dioxide radical anion (CO2•-) recently becomes appreciated in halogenated contaminants elimination; nevertheless, its application has been restricted by insufficient mechanistic understanding. Herein, we provided a quantitative insight into the kinetics and mechanisms of CO2•- mediated dehalogenation of halogenated alkanes. A CO2•- dominated UV254/H2O2/HCOO- system has been successfully established and demonstrated for effective elimination of 7 kinds of halogenated alkanes (71.3 % to 100 % of removal). Using a laser flash photolysis technology, the second-order rate constants of CO2•- ( [Formula: see text] ) reacting with CCl4, CHCl3 and CH2Cl2 were firstly reported, to be 2.5 × 108, 6.2 × 107 and 5.8 × 106 M-1s-1, respectively. [Formula: see text] presented a significant negative correlation with the lowest unoccupied molecular orbital energy (ELUMO) of chlorinated alkanes, proving that the enhanced dehalogenation of CO2•- was attributed by direct electron transfer mechanism. A fitting model was developed accordingly for [Formula: see text] prediction. This study also demonstrated that the CO2•- mediated ARP effectively removed halogenated alkanes regardless of pH condition (6.0∼9.0) and bicarbonate concentrations. These findings are significant in advancing the scientific understanding of CO2•- mediated ARP. This reductive process a promising control strategy for halogenated contaminants, such as polyfluoroalkyl substances (PFAS) and halogenated pharmaceuticals.

Multifunctional Conductive Hydrogel Interface for Bioelectronic Recording and Stimulation.

The past few decades have witnessed the rapid advancement and broad applications of flexible bioelectronics, in wearable and implantable electronics, brain-computer interfaces, neural science and technology, clinical diagnosis, treatment, etc. It is noteworthy that soft and elastic conductive hydrogels, owing to their multiple similarities with biological tissues in terms of mechanics, electronics, water-rich, and biological functions, have successfully bridged the gap between rigid electronics and soft biology. Multifunctional hydrogel bioelectronics, emerging as a new generation of promising material candidates, have authentically established highly compatible and reliable, high-quality bioelectronic interfaces, particularly in bioelectronic recording and stimulation. This review summarizes the material basis and design principles involved in constructing hydrogel bioelectronic interfaces, and systematically discusses the fundamental mechanism and unique advantages in bioelectrical interfacing with the biological surface. Furthermore, an overview of the state-of-the-art manufacturing strategies for hydrogel bioelectronic interfaces with enhanced biocompatibility and integration with the biological system is presented. This review finally exemplifies the unprecedented advancement and impetus toward bioelectronic recording and stimulation, especially in implantable and integrated hydrogel bioelectronic systems, and concludes with a perspective expectation for hydrogel bioelectronics in clinical and biomedical applications.

The Reciprocal Relations between Parental Psychological Control and Social Anxiety and the Mediating Role of Self-Concept Clarity Among Chinese Early Adolescents.

Although parental psychological control has been well-documented as a significant predictor of social anxiety among adolescents, few studies examine how changes in parental psychological control and adolescent social anxiety are reciprocally related at the within-person level, especially in Chinese culture. This longitudinal study examined reciprocal relations between parental psychological control and social anxiety, and the potential mediating role of self-concept clarity, by disentangling between- and within-person effects. A total of 4731 students (44.9% girls; Mage = 10.91 years, SD = 0.72) participated in a four-wave longitudinal study with 6-month intervals. Results from random intercept cross-lagged panel modeling indicated that parental psychological control directly predicted social anxiety, and vice versa. Parental psychological control indirectly predicted social anxiety via self-concept clarity, and social anxiety also indirectly predicted parental psychological control via self-concept clarity. These findings reveal a vicious cycle of mutual influence between parental psychological control and adolescent social anxiety in Chinese youth, and highlight the crucial role of self-concept clarity in the interplay between parenting and adolescent social functioning.

Mutations in the NUP93, NUP107 and NUP160 genes cause steroid-resistant nephrotic syndrome in Chinese children.

BACKGROUND: The variants of nucleoporins are extremely rare in hereditary steroid-resistant nephrotic syndrome (SRNS). Most of the patients carrying such variants progress to end stage kidney disease (ESKD) in their childhood. More clinical and genetic data from these patients are needed to characterize their genotype-phenotype relationships and elucidate the role of nucleoporins in SRNS. METHODS: Four patients of SRNS carrying biallelic variants in the NUP93, NUP107 and NUP160 genes were presented. The clinical and molecular genetic characteristics of these patients were summarized, and relevant literature was reviewed. RESULTS: All four patients in this study were female and initially presented with SRNS. The median age at the onset of the disease was 5.08 years, ranging from 1 to 10.5 years. Among the four patients, three progressed to ESKD at a median age of 7 years, ranging from 1.5 to 10.5 years, while one patient reached stage 3 chronic kidney disease (CKD3). Kidney biopsies revealed focal segmental glomerulosclerosis in three patients. Biallelic variants were detected in NUP93 in one patient, NUP107 in two patients, as well as NUP160 in one patient respectively. Among these variants, five yielded single amino acid substitutions, one led to nonsense mutation causing premature termination of NUP107 translation, one caused a single nucleotide deletion resulting in frameshift and truncation of NUP107. Furthermore, one splicing donor mutation was observed in NUP160. None of these variants had been reported previously. CONCLUSION: This report indicates that biallelic variants in NUP93, NUP107 and NUP160 can cause severe early-onset SRNS, which rapidly progresses to ESKD. Moreover, these findings expand the spectrum of phenotypes and genotypes and highlight the importance of next-generation sequencing in elucidating the molecular basis of SRNS and allowing rational treatment for affected individuals.