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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP‐43 aggregates. Recent evidence has been indicated that phosphorylated TDP‐43 (pTDP‐43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP‐43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP‐43 detectable in routine biopsied muscles? (ii) Can detection of pTDP‐43 aggregation discriminate between ALS and non‐ALS patients? (iii) Can pTDP‐43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non‐ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP‐43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP‐43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non‐ALS controls (16/54; p < 0.001). The pTDP‐43 aggregates were mainly close to the sarcolemma. Using a semi‐quantified pTDP‐43 aggregates score, we applied a cut‐off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP‐43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof‐of‐concept for the detection of pTDP‐43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS. [ABSTRACT FROM AUTHOR]

Federated Learning (FL) enables decentralized data utilization while maintaining edge user privacy, but it faces challenges due to statistical heterogeneity. Existing approaches address client drift and data heterogeneity issues. However, real-world settings often involve low-quality data with noisy features, such as covariate drift or adversarial samples, which are usually ignored. Noisy samples significantly impact the global model's accuracy and convergence rate. Assessing data quality and selectively aggregating updates from high-quality clients is crucial, but dynamically perceiving data quality without additional computations or data exchanges is challenging. In this paper, we introduce the FedDQA (Federated learning via Data Quality-Aware) (FedDQA) framework. We discover increased data noise leads to slower loss reduction during local model training. We propose a loss sharpness-based Data-Quality-Awareness (DQA) metric to differentiate between high-quality and low-quality data. Based on the DQA, we design a client selection algorithm that strategically selects participant clients to reduce the negative impact of noisy clients. Experiment results indicate that FedDQA significantly outperforms the baselines. Notably, it achieves up to a 4% increase in global model accuracy and demonstrates faster convergence rates. [ABSTRACT FROM AUTHOR]

Objective: Human T‐cell leukemia virus type 1‐associated myelopathy (HAM) is a chronic, progressive, inflammatory disease with unclear pathogenesis and no effective treatments. We aimed to investigate a novel mechanistic theory and treat HAM patients with rituximab, which can deplete CD20+ B lymphocytes in circulation. Methods: Single‐cell RNA sequencing (scRNA‐seq) data was analyzed to identify HTLV‐1‐associated B cells and their effect on T cells. An observational analysis of our HAM cohort was conducted to elucidate changes in the immunological microenvironment of these patients. Peripheral blood mononuclear cells (PBMC) from HAM patients were isolated to explore the efficacy of B cell depletion in vitro. To assess the effect of B‐cell depletion on HAM patients, eligible participants in our cohort received rituximab therapy (NCT04004819). Results: ScRNA‐seq results suggest a significant effect of HTLV‐1‐associated B cells on T cells. Additionally, HTLV‐1 was found to infect B cells and depletion of B cells inhibited the proliferation of T cells. Number of B cells in HAM patients had positive correlation with the proviral load and infected cell counts. Depletion of B cells led to a reduction in HTLV‐1 proviral load in vitro. Furthermore, in clinical trial, 14 HAM patients were enrolled. Three patients (21.4%) who received rituximab failed to achieve remission, compared to 24 (85.7%) patients received any other therapy that failed to achieve remission. With a low level of circulating B cells, the proportion of Ki67‐positive cells in CD4+ T cells fell. Interpretation: This study provided evidence that depleting B‐lymphocytes is an innovative strategy for treating patients with HAM and broadens the understanding of the role of B cells in infectious immunity. [ABSTRACT FROM AUTHOR]

Ancient paintings, as a vital component of cultural heritage, encapsulate a profound depth of cultural significance. Over time, they often suffer from different degradation conditions, leading to damage. Existing ancient painting inpainting methods struggle with semantic discontinuities, blurred textures, and details in missing areas. To address these issues, this paper proposes a generative adversarial network (GAN)-based ancient painting inpainting method named RG-GAN. Firstly, to address the inconsistency between the styles of missing and non-missing areas, this paper proposes a Regional Attention-Style Transfer Module (RASTM) to achieve complex style transfer while maintaining the authenticity of the content. Meanwhile, a multi-scale fusion generator (MFG) is proposed to use the multi-scale residual downsampling module to reduce the size of the feature map and effectively extract and integrate the features of different scales. Secondly, a multi-scale fusion mechanism leverages the Multi-scale Cross-layer Perception Module (MCPM) to enhance feature representation of filled areas to solve the semantic incoherence of the missing region of the image. Finally, the Global Context Perception Discriminator (GCPD) is proposed for the deficiencies in capturing detailed information, which enhances the information interaction across dimensions and improves the discriminator's ability to identify specific spatial areas and extract critical detail information. Experiments on the ancient painting and ancient Huaniao++ datasets demonstrate that our method achieves the highest PSNR values of 34.62 and 23.46 and the lowest LPIPS values of 0.0507 and 0.0938, respectively. [ABSTRACT FROM AUTHOR]

Following the handover of sovereignty from Britain to China in 1997, Hong Kong embarked on a renewed exploration of its cultural identity. This quest for identity found a powerful resonance in the late-1997 musical adaptation of Pygmalion, titled Yao Tiao Shu Nv (Lovely is This Noble Lady). This article argues that the musical's success stemmed from the underlying themes of colonialism and postcolonialism present in George Bernard Shaw's original work. By recreating the setting, the characterization, and the soundscape of a Hong Kong in its early colonial years, the adaptation negotiates cultural identity within the specific context of postcolonial Hong Kong. [ABSTRACT FROM AUTHOR]

Objective: Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients. Methods: Whole‐exome sequencing was performed for 106 PRRT2‐negative PKD probands. The functional impact of the genetic variants was investigated in HEK293T cells and Drosophila. Results: Heterozygous variants in KCNJ10 were identified in 11 individuals from 8 unrelated families, which accounted for 7.5% (8/106) of the PRRT2‐negative probands. Both co‐segregation of the identified variants and the significantly higher frequency of rare KCNJ10 variants in PKD cases supported impacts from the detected KCNJ10 heterozygous variants on PKD pathogenesis. Moreover, a KCNJ10 mutation‐carrying father from a typical EAST/SeSAME family was identified as a PKD patient. All patients manifested dystonia attacks triggered by sudden movement with a short episodic duration. Patch‐clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient‐derived variants, indicating a loss‐of‐function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock‐in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia‐specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes. Interpretation: Our study established haploinsufficiency resulting from heterozygous variants in KCNJ10 can be understood as a previously unrecognized genetic cause for PKD and provided evidence of glial involvement in the pathophysiology of PKD. ANN NEUROL 2024;96:758–773 [ABSTRACT FROM AUTHOR]

The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ’s metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development. Using the SomaScan proteomics platform on 434 patients with biopsy-confirmed kidney disease, we here identify plasma biomarkers associated with ATI severity. We employ regional transcriptomics and proteomics, single-cell RNA sequencing, and pathway analysis to explore biomarker protein and gene expression and enriched biological pathways. Additionally, we examine ATI biomarker associations with acute kidney injury (AKI) in the Kidney Precision Medicine Project (KPMP) (n = 44), the Atherosclerosis Risk in Communities (ARIC) study (n = 4610), and the COVID-19 Host Response and Clinical Outcomes (CHROME) study (n = 268). Our findings indicate 156 plasma proteins significantly linked to ATI with osteopontin, macrophage mannose receptor 1, and tenascin C showing the strongest associations. Pathway analysis highlight immune regulation and organelle stress responses in ATI pathogenesis.Acute tubular injury (ATI) significantly contributes to many kidney diseases. Here, the authors identify several immune response and cellular stress plasma proteins linked to ATI severity and acute kidney injury, which may aid in non-invasive ATI assessment. [ABSTRACT FROM AUTHOR]

Image inpainting aims to restore the damaged information in images, enhancing their readability and usability. Ancient paintings, as a vital component of traditional art, convey profound cultural and artistic value, yet often suffer from various forms of damage over time. Existing ancient painting inpainting methods are insufficient in extracting deep semantic information, resulting in the loss of high-frequency detail features of the reconstructed image and inconsistency between global and local semantic information. To address these issues, this paper proposes a Generative Adversarial Network (GAN)-based ancient painting inpainting method using multi-layer feature enhancement and frequency perception, named MFGAN. Firstly, we design a Residual Pyramid Encoder (RPE), which fully extracts the deep semantic features of ancient painting images and strengthens the processing of image details by effectively combining the deep feature extraction module and channel attention. Secondly, we propose a Frequency-Aware Mechanism (FAM) to obtain the high-frequency perceptual features by using the frequency attention module, which captures the high-frequency details and texture features of the ancient paintings by increasing the skip connections between the low-frequency and the high-frequency features, and provides more frequency perception information. Thirdly, a Dual Discriminator (DD) is designed to ensure the consistency of semantic information between global and local region images, while reducing the discontinuity and blurring differences at the boundary during image inpainting. Finally, extensive experiments on the proposed ancient painting and Huaniao datasets show that our proposed method outperforms competitive image inpainting methods and exhibits robust generalization capabilities. [ABSTRACT FROM AUTHOR]

Simple Summary: Intervertebral disc degeneration (IDD) occurs due to damage and loss of nucleus pulposus (NP) cells. This study investigated the protective effects of Raphanus sativus Linne (RSL), commonly known as radish, against oxidative stress caused by H2O2 in human NP cells and its ability to inhibit TREM2, a protein that induces apoptosis and degeneration in NP cells. RSL significantly improved cell survival by reducing the apoptosis markers cleaved caspase-3 and Bax and increasing Bcl2. It also enhanced mRNA levels of ACAN and Col2a1, important for NP cell function, and reduced levels of ADAMTS-4, ADAMTS-5, MMP3, and MMP13, which are involved in NP cell degeneration. Additionally, RSL downregulated TREM2 expression, which is elevated by H2O2 and causes disc degeneration. Overall, RSL extracts support human NP cells under oxidative stress and may help prevent IDD by regulating key degeneration pathways, particularly TREM2. Intervertebral disc degeneration (IDD) progresses owing to damage and depletion of nucleus pulposus (NP) cells. Cytoprotection mitigates oxidative stress, nutrient deprivation, and mechanical stress, which lead to cell damage and necrosis. We aimed to examine the protective effect of Raphanus sativus Linne (RSL), common radish, against oxidative stress by H2O2 in human NP cells and whether the RSL extracts can inhibit triggering receptor expressed on myeloid cells 2 (TREM2), an inducer of apoptosis and degeneration in NP cells. We administered hydrogen peroxide (H2O2) to cultured human NP cells treated with RSL extracts. We used immunoblotting and quantitative PCR to investigate expression of the apoptosis-associated proteins in cultured cells. RSL significantly enhanced cell survival by suppressing the activation of cleaved caspase-3 and Bax. In contrast, RSL extract increased Bcl2 concentration to downregulate apoptosis. Additionally, RSL treatment notably enhanced the mRNA levels of ACAN and Col2a1 while significantly reducing those of ADAMTS-4, ADAMTS-5, MMP3, and MMP13, key genes involved in NP degeneration. While H2O2 elevated TREM2 expression, causing disc degeneration, RSL downregulated TREM2 expression. Thus, our findings imply that RSL supports human NP cells under oxidative stress and regulates the pathways underlying disc degeneration, particularly TREM2, and that RSL extracts may potentially prevent IDD. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) affecting 1 in 3500–5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient's DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction. Duchenne muscular dystrophy (DMD) results from mutations in the DMD. Here the authors report using adenine base editing of exon splice sites to restore dystrophin expression and muscle function in a humanized mouse model of DMD with exon 50 and 51 of mouse DMD gene replaced with human exon 50. [ABSTRACT FROM AUTHOR]

Introduction: Spinal muscular atrophy (SMA) is a rare, autosomal recessive, neuromuscular disease that leads to progressive muscular weakness and atrophy. Nusinersen, an antisense oligonucleotide, was approved for SMA in China in February 2019. We report interim results from a post-marketing surveillance phase 4 study, PANDA (NCT04419233), that collects data on the safety, efficacy, and pharmacokinetics of nusinersen in children with SMA in routine clinical practice in China. Methods: Participants enrolled in PANDA will be observed for 2 years following nusinersen treatment initiation. The primary endpoint is the incidence of adverse events (AEs)/serious AEs (SAEs) during the treatment period. Efficacy assessments include World Health Organization (WHO) Motor Milestones assessment, the Hammersmith Infant Neurological Examination (HINE), and ventilation support. Plasma and cerebrospinal fluid (CSF) concentrations of nusinersen are measured at each dose visit. Results: Fifty participants were enrolled as of the January 4, 2023, data cutoff: 10 with infantile-onset (≤ 6 months) and 40 with later-onset (> 6 months) SMA. All 50 participants have received at least one dose of nusinersen; 6 have completed the study. AEs were experienced by 45 (90%) participants and were mostly mild/moderate; no AEs led to nusinersen discontinuation or study withdrawal. Eleven participants experienced SAEs, most commonly pneumonia (n = 9); none were considered related to study treatment. Stability or gain of WHO motor milestone was observed and mean HINE-2 scores improved in both subgroups throughout the study. No serious respiratory events occurred, and no permanent ventilation support was initiated during the study. Pre-dose nusinersen CSF concentrations increased steadily through the loading-dose period, with no accumulation in plasma after multiple doses. Conclusion: Nusinersen was generally well tolerated with an acceptable overall safety profile, consistent with the known safety of nusinersen. Efficacy, safety, and nusinersen exposure are consistent with prior observations. These results support continuing PANDA and evaluation of nusinersen in Chinese participants with SMA. Trial Registration: ClinicalTrials.gov identifier, NCT04419233. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Papillary fibroelastoma is the most common type of benign primary cardiac tumor and is usually asymptomatic. However, tumor fragments or surface thrombus can embolize and cause transient ischemic attacks, strokes, or myocardial infarction. This report describes a 76-year-old woman who presented with dysarthria and rightsided weakness due to a stroke associated with a left atrial papillary fibroelastoma. Case Report: A 76-year-old woman visited the Emergency Department because she had right-sided weakness and dysarthria from 12 h ago. Brain magnetic resonance image was done at the Emergency Department, showing multiple small embolic, acute infarction in left basal ganglia and fronto-temporo-parietal lobes. Transthoracic and transesophageal echocardiogram showed a hypermobile echogenic mass (0.8×1.5 cm) with villous surface on the orifice of left atrial appendage. Twenty-four-hour Holter monitoring was performed to evaluate the cause of cerebral infarction, and there was no paroxysmal atrial fibrillation. Thoracic computed tomography angiography also showed a sea anemone-shaped mass around the left atrial appendage. Cardiac tumor excision was done via a lower partial sternotomy. Histopathologic analysis showed multiple delicate fronds, and the avascular fibroelastic cores were lined by a single layer of CD31-positive endothelial cells. Histopathologic findings were consistent with papillary fibroelastoma. The patient was discharged without any other complications on day 30 of hospitalization. Conclusions: This case highlights the importance of cardiac imaging in patients with acute stroke, including transthoracic and transesophageal echocardiography, which can show the typical imaging features of papillary fibroelastoma and other intracardiac sources of embolus. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) often leads to interstitial lung disease (ILD), significantly affecting patient outcomes. This study explored the diagnostic accuracy of a multi-biomarker approach to offer a more efficient and accessible diagnostic strategy for RA-associated ILD (RA-ILD). Methods: Patients diagnosed with RA, with or without ILD, at Beijing Tiantan Hospital from October 2019 to October 2023 were analyzed. A total of 125 RA patients were included, with 76 diagnosed with RA-ILD. The study focused on three categories of indicators: tumor markers, inflammatory indicators, and disease activity measures. The heatmap correlation analysis was employed to analyze the correlation among these indicators. Logistic regression was used to determine odds ratios (OR) for indicators linked to RA-ILD risk. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of these indicators for RA-ILD. Results: The results of logistic regression analysis showed that tumor markers (carbohydrate antigen 19–9 (CA19-9), carbohydrate antigen 125 (CA125), and cytokeratin 19 fragment (CYFRA21-1)), as well as inflammatory indicators (neutrophil, neutrophil-to-lymphocyte ratio (NLR), platelet, C-reactive protein (CRP)) and disease activity measures (disease activity score-28-CRP (DAS28-CRP), rheumatoid factor (RF), and anti-cyclic peptide containing citrulline (anti-CCP)), were significantly associated with RA-ILD. The correlation coefficients among these indicators were relatively low. Notably, the combination indicator 4, which integrated the aforementioned three categories of biomarkers, demonstrated improved diagnostic accuracy with an AUC of 0.857. Conclusion: The study demonstrated that combining tumor markers, inflammatory indicators, and disease activity measures significantly enhanced the prediction of RA-ILD. Key Points • Multidimensional strategy: Integrated tumor markers, inflammatory indicators, and disease activity measures to enhance early detection of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). • Diagnostic accuracy: Employed heatmap correlation and logistic regression, identifying significant associations and improving diagnostic accuracy with a multidimensional biomarker combination. • Superior performance: The combined multidimensional biomarker strategy demonstrated higher diagnostic precision compared to individual or dual-category indicators. • Clinical relevance: Offers a promising, accessible approach for early detection of RA-ILD in clinical settings, potentially improving patient outcomes. [ABSTRACT FROM AUTHOR]

Rolling bearings are prone to failure due to the complexity and serious operational environment of rotating equipment. Intelligent fault diagnosis based on convolutional neural networks (CNNs) has become an effective tool to ensure the reliable operation of rolling bearings. However, interference caused by environmental noise and variable working conditions can affect the data. To solve this problem, we propose an improved fault diagnosis method called deep convolutional neural network based on multi-scale features and mutual information (MMDCNN). In our approach, a multi-scale convolutional layer is placed at the front end of a 1D_CNN to maximize the retention of the multi-scale initial features. Meanwhile, the key fault features are further enhanced adaptively by introducing a self-attention mechanism. Then, the composite loss function is constructed by maximizing mutual information as an auxiliary loss based on cross-entropy loss; thus, the proposed method can extract robust fault features with high generalization performance. To demonstrate the superiority of MMDCNN, we compared the performance of our scheme with several existing deep learning models on two datasets. The results show that the proposed model successfully achieves bearing fault diagnosis with interference from noise and variable working conditions, possessing a powerful fault feature extraction capability. [ABSTRACT FROM AUTHOR]

In adverse foggy weather conditions, images captured are adversely affected by natural environmental factors, resulting in reduced image contrast and diminished visibility. Traditional image dehazing methods typically rely on prior knowledge, but their efficacy diminishes in practical, complex environments. Deep learning methods have shown promise in single-image dehazing tasks, but often struggle to fully leverage depth and edge information, leading to blurred edges and incomplete dehazing effects. To address these challenges, this paper proposes a deep-guided bilateral grid feature fusion dehazing network. This network extracts depth information through a dedicated module, derives bilateral grid features via Unet, employs depth information to guide the sampling of bilateral grid features, reconstructs features using a dedicated module, and finally estimates dehazed images through two layers of convolutional layers and residual connections with the original images. The experimental results demonstrate the effectiveness of the proposed method on public datasets, successfully removing fog while preserving image details. [ABSTRACT FROM AUTHOR]

The choice of treatment for lumbar spinal stenosis (LSS) depends on symptom severity. When severe motor issues with urinary dysfunction are not present, conservative treatment is often considered to be the priority. One such conservative treatment is epidural injection, which is effective in alleviating inflammation and the pain caused by LSS-affected nerves. In this study, Shinbaro2 (Sh2), pharmacopuncture using natural herbal medicines for patients with disc diseases, is introduced as an epidural to treat LSS in a rat model. The treatment of primary sensory neurons from the rats' dorsal root ganglion (DRG) neurons with Sh2 at various concentrations (0.5, 1, and 2 mg/mL) was found to be safe and non-toxic. Furthermore, it remarkably stimulated axonal outgrowth even under H2O2-treated conditions, indicating its potential for stimulating nerve regeneration. When LSS rats received epidural injections of two different concentrations of Sh2 (1 and 2 mg/kg) once daily for 4 weeks, a significant reduction was seen in ED1+ macrophages surrounding the silicone block used for LSS induction. Moreover, epidural injection of Sh2 in the DRG led to a significant suppression of pain-related factors. Notably, Sh2 treatment resulted in improved locomotor recovery, as evaluated by the Basso, Beattie, and Bresnahan scale and the horizontal ladder test. Additionally, hind paw hypersensitivity, assessed using the Von Frey test, was reduced, and normal gait was restored. Our findings demonstrate that epidural Sh2 injection not only reduced inflammation but also improved locomotor function and pain in LSS model rats. Thus, Sh2 delivery via epidural injection has potential as an effective treatment option for LSS. [ABSTRACT FROM AUTHOR]

Oxidative stress‐induced neuronal damage is a significant factor contributing to spinal cord injury. Although previous research has shown that Fructus Ligustri Lucidi (FLL) has neuroprotective benefits in SH‐SY5Y, BV2, and PC12 cells, its impact on primary spinal cord neurons, which more accurately reflect the characteristics of central nervous system neurons, remains unexplored. This research investigated how FLL can protect rat primary spinal cord neurons from injury triggered by hydrogen peroxide (H2O2)‐mediated oxidative stress. Cell viability, generation of reactive oxygen species (ROS), upregulation of inducible nitric oxide synthase (iNOS), activation of the Nrf2/HO‐1 antioxidant pathway, and mitochondrial superoxide were assessed. Rat primary spinal cord neurons were not adversely affected by concentrations of FLL extract up to 100 μg/mL. Furthermore, FLL extract showed a significant protective effect against H2O2‐induced neuronal toxicity at 10–100 μg/mL. Fluorescence‐activated cell sorting analysis revealed that FLL extract inhibited H2O2‐induced ROS generation in a dose‐dependent manner. Immunocytochemistry and gene expression analysis confirmed that FLL extract reduced the overexpression of iNOS induced by H2O2 and enhanced the stimulation of the Nrf2/HO‐1 pathway, crucial for antioxidant responses. In conclusion, FLL extract demonstrated neuroprotective effects on rat primary spinal cord neurons against the oxidative stress induced by H2O2. FLL extract effectively preserved cell viability, reduced ROS generation, suppressed iNOS overexpression, and activated the Nrf2/HO‐1 antioxidant pathway. These results highlight the capacity of FLL extract as a neuroprotective agent against oxidative stress‐related spinal neuron damage. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the impact of interpersonal sensitivity on the subjective well-being of accompanying children of migrant workers and the role of perception of exclusion and peer support in the process. Methods: A questionnaire survey was conducted among 304 migrant workers' accompanying children and 501 urban children in grades 4– 9 in seven schools in Jiangxi Province, China. Hierarchical regression and bootstrap analysis were used. Results: Interpersonal sensitivity not only had a significant direct negative effect on the subjective well-being of migrant workers' accompanying children (β= − 0.27, 95% CI = [− 0.37, − 0.17]), but also had an indirect effect through perception of exclusion (β= − 0.06, 95% CI = [− 0.11, − 0.03]). Peer support negatively moderated the relationship between interpersonal sensitivity and perception of exclusion (β= − 0.18, 95% CI = [− 0.28, − 0.08]) and the mediating effect of perceptions of exclusion between interpersonal sensitivity and subjective well-being (β = 0.06, CI = [0.02, 0.11]). Conclusion: The subjective well-being of migrant children is indeed lower than that of urban children, and one of the most important reasons is their higher interpersonal sensitivity. Interpersonal sensitivity not only directly reduces their subjective well-being, but also reduces it by triggering their perception of exclusion, while peer support can effectively mitigate this negative effect. Therefore, one way to improve the subjective well-being of these children is to reduce their excessive interpersonal sensitivity. Their parents should help them to adapt to urban life, to develop correct professional values and to deal correctly with "occupational stigma", to overcome feelings of inferiority, while communities can create specialized activity centers to provide more social opportunities and psychological counseling services for these children. [ABSTRACT FROM AUTHOR]

In the VUCA era, organizations that are bound by rigid regulations often find themselves lagging behind in their ability to adapt to the dynamic external environment, consequently missing out on potential opportunities. Organizational innovation often stems from employees' proactive and spontaneous pro-social rule breaking behavior. This study, based on situation-strength theory under the framework of trait activation, investigates the impact of proactive personality on employees' pro-social rule breaking behavior and its underlying mechanisms through a scenario experiment and a questionnaire survey. The results reveal that proactive personality is not significant for pro-social rule breaking behavior, with one positive and one negative effect counteracting each other. Proactive personality positively influences promotion focus, but it also negatively affects pro-social rule breaking behavior through promotion focus. Moreover, psychological safety climate plays a weakening moderating role between promotion focus and pro-social rule breaking behavior. With an increase in the level of psychological safety climate, the negative effect of proactive personality on prosocial rule-breaking behavior through promotion focus gradually attenuates. This study offers novel insights for a more comprehensive comprehension of the role of proactive personality on favorable organizational behavior and deepens the understanding of the effect mechanisms and boundary conditions in the association between proactive personality and pro-social rule-breaking behavior. [ABSTRACT FROM AUTHOR]

Career choice research has attracted the attention of recruiters and young graduates. The study aims to investigate the psychological factors that influence college students’ employment choices. As a result, data for the study were gathered from 250 final-year college students in China via an online questionnaire survey. The study identified the psychological barriers faced by college students during job interviews through interviews with 120 h recruiters. The SPPS tool is used for data analysis. The study identified personal interest, self-efficacy, and self- esteem; social responsibilities; confidence; professional development opportunities; and future orientation as the important psychological factors that influence the career choice of college students. The study also found that the barriers faced by the college students during the interview were anxiety, inferiority complex, cowardice, and pride. Therefore, the study suggests that the college provides job-oriented training for college students’ employment choices. The college should take the initiative to provide students with career opportunities and proper training to avoid psychological barriers during interviews. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are commonly used in the treatment of chronic inflammatory conditions. However, the administration of high doses and long-term use of GCs can induce muscle atrophy (MA) in patients, leading to a decline in quality of life and increased mortality. MA leads to protein degradation in skeletal muscle, resulting in a reduction of muscle mass. This process is triggered by GCs like dexamethasone (DEX), which induce the expression of E3 ubiquitin ligases, namely Atrogin-1 and muscle RING-finger protein-1 (MuRF1). In this study, we examined the anti-MA potential of Luffa cylindrica Roemer (LCR) on DEX-treated primary skeletal myotubes. Primary skeletal myotubes stimulated with LCR alone resulted in a significant upregulation of myotube development, characterized by an increase in both the number and diameter of myotubes. Contrastingly, combined treatment with LCR and DEX reduced the expression of Atrogin-1, while treatment with DEX alone induced the expression of MuRF1. Furthermore, LCR treatment successfully restored the number and diameter of myotubes that had been diminished by DEX treatment. These findings suggest that LCR holds potential for treating MA, as an accelerating effect on muscle development and anti-MA effects on primary skeletal muscle cells were observed. [ABSTRACT FROM AUTHOR]

In this study, the effects of earing in a sheared billet of S25C steel formed during rod shearing in an automatic multi-stage cold forging (AMSCF) process for an automobile wheel nut were experimentally and numerically investigated. Precision forging simulations with an emphasis on rod shearing were conducted using the implicit elastoplastic finite element method with a tetrahedral MINI-element scheme. AMSCF of an automobile wheel nut involves the use of a converging or near-conical die that shows a gradual reduction in its cross-sectional area. Our results showed that the shearing-induced earing plays the role of a pivot during balancing of the material inside the die cavity in the early stroke, before significant material contact. Earing formation resulted in a wobble motion of the material that accompanied the rigid-body motion. This ultimately led to a change in the center of mass of the material and unbalanced loading. Earing had a significant influence on the local high-cycle fatigue (HCF) fracture of die insets, especially in the cold forging of nut-like short products. The stress concentration on the die was attributed to asymmetric localized contact between the material and critical die corner, leading to changes in the mass center. Taken together, our results indicate that sheared billet characterization should account for earings with roll-overs and inclined surfaces to not only better predict the HCF life of die parts but also to optimize the forging outcome, particularly for safety products such as automobile wheel nuts. [ABSTRACT FROM AUTHOR]

Background: Improving the job engagement of health professionals can effectively enhance the quality of their medical services. However, few studies have investigated whether and how perceived professional benefits affect job engagement. Based on resource conservation theory, this study explored the effect of the influence of perceived professional benefits on job engagement, and also examined the mediating role of psychological availability and the moderating role of future perceived professional benefits. Methods: A cross-sectional study was conducted in six tertiary hospitals and seven secondary hospitals in Liu Panshui, a city in western China. A total of 1,406 valid questionnaires were obtained and analysed by using correlation analysis, hierarchical regression analysis, and bootstrap tests. Result: The study found a significant positive association between health professionals' perceived professional benefits and their job engagement. Additionally, psychological availability was found to mediate this relationship. Future perceived professional benefits not only positively moderate this relationship between perceived professional benefits on health professionals' psychological availability but also positively moderate the mediating role of psychological availability between perceived professional benefits and job engagement. Conclusion: Improving health professionals' perceived professional benefits can enhance their job engagement by increasing their psychological availability. However, for health professionals with low future perceived professional benefits, this improvement may disappear. Therefore, it is important to enhance both their current and future perceived professional benefits to improve their job engagement. [ABSTRACT FROM AUTHOR]

Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2–92.2% for deferiprone and 90–100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence. [ABSTRACT FROM AUTHOR]

Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2–92.2% for deferiprone and 90–100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence. [ABSTRACT FROM AUTHOR]

Background: Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment. Objective: To characterize cognitive impairment in SCA3 and investigate the cerebellum–cognition associations. Methods: This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments. Results: Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments. Conclusions: Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s). [ABSTRACT FROM AUTHOR]

Four new alkaloids (1 − 4), together with five known ones (5 − 9), were isolated from the bulbs of Dactylicapnos scandens. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolates were tested for their ability to modulate neuronal Ca2+ mobilization in primary cultured neocortical neurons. Compound 8 inhibited spontaneous Ca2+ oscillations at low micromolar concentrations. [ABSTRACT FROM AUTHOR]

Objective: Analyzing the chemical composition and blood-entry components of Nourishing Blood Diuretic Formula (NBDF) by Liquid Chromatography-Mass Spectrometry (LC-MS), and analyzing the mechanism of NBDF in the treatment of chronic renal failure by combining network pharmacology and molecular docking technology. Methods: The prototype components were obtained by LC-MS, and the targets of the prototype components and the targets for the treatment of chronic renal failure (CRF) were predicted by network pharmacology to obtain the common targets of the drug and the disease, which were then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and molecular docking was carried out between the compounds of the prototype components and the key targets, so as to screen out the active ingredients, the targets and the signaling pathways that were closely related to the efficacy of NBDF. Results: Synthesizing the test information, 125 compounds were identified from the solution of NBDF, and 48 blood-entry components were identified from rat plasma containing the drug, including 6 prototypical components, and 102 potential targets of action, 515 GO entries, and 133 KEGG pathways were obtained from the web-based pharmacological analyses, and molecular docking was performed to obtain the binding of the 6 prototypical component compounds and the 9 key targets, and the formononetin, emodin, epicatechin, chlorogenic acid, sennoside A, and astragaloside III were hypothesized to be the active components of NBDF in the treatment of CRF. Conclusion: This study initially demonstrated that Nourishing Blood and Diuretic Formula exert its therapeutic effects on CRF through multicomponents, multitargets, and multimethods, and elucidated its pharmacological material basis and therapeutic mechanism. [ABSTRACT FROM AUTHOR]

The development of a stable and efficient non‐noble metal catalyst with both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is paramount to achieving the widespread application of Zn‐air batteries (ZABs) but remains a great challenge. Herein, a novel Co3Fe7 alloy nanoparticle dispersed on Se, N co‐doped graphitic carbon (denoted as CoFe/Se@CN) was prepared through a facile hydrothermal and pyrolysis process. The synthesized CoFe/Se@CN exhibits outstanding ORR and OER properties with an ultralow potential gap of 0.625 V, which is mainly attributed to the abundant porous structure, the rich structural defects formed by doping Se atoms, and the strong synergistic effects between the CoFe alloys and graphitic carbon nanosheet. Furthermore, the ZAB fabricated by CoFe/Se@CN shows a high peak power density of 160 mW cm−2 and a large specific capacity of 802 mA h g−1 with favorable cycling stability, outperforming that of Pt/C+RuO2. Our study offers a plausible strategy to explore bifunctional carbon‐based materials with efficient electrocatalytic properties for rechargeable ZABs. [ABSTRACT FROM AUTHOR]

Background: Hereditary spastic paraplegias (HSP) are neurologic disorders characterized by progressive lower‐extremity spasticity. Despite the identification of several HSP‐related genes, many patients lack a genetic diagnosis. Objectives: The aims were to confirm the pathogenic role of biallelic COQ4 mutations in HSP and elucidate the clinical, genetic, and functional molecular features of COQ4‐associated HSP. Methods: Whole exome sequences of 310 index patients with HSP of unknown cause from three distinct populations were analyzed to identify potential HSP causal genes. Clinical data obtained from patients harboring candidate causal mutations were examined. Functional characterization of COQ4 variants was performed using bioinformatic tools, single‐cell RNA sequencing, biochemical assays in cell lines, primary fibroblasts, induced pluripotent stem cell–derived pyramidal neurons, and zebrafish. Results: Compound heterozygous variants in COQ4, which cosegregated with HSP in pedigrees, were identified in 7 patients from six unrelated families. Patients from four of the six families presented with pure HSP, whereas probands of the other two families exhibited complicated HSP with epilepsy or with cerebellar ataxia. In patient‐derived fibroblasts and COQ4 knockout complementation lines, stable expression of these missense variants exerted loss‐of‐function effects, including mitochondrial reactive oxygen species accumulation, decreased mitochondrial membrane potential, and lower ubiquinone biosynthesis. Whereas differentiated pyramidal neurons expressed high COQ4 levels, coq4 knockdown zebrafish displayed severe motor dysfunction, reflecting motor neuron dysregulation. Conclusions: Our study confirms that loss‐of‐function, compound heterozygous, pathogenic COQ4 variants are causal for autosomal recessive pure and complicated HSP. Moreover, reduced COQ4 levels attributable to variants correspond with decreased ubiquinone biosynthesis, impaired mitochondrial function, and higher phenotypic disease severity. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: To explore the influence of postoperative body mass index (BMI) change on postoperative quality of life (QOL) in patients undergoing radical cystectomy (RC) plus modified single stoma cutaneous ureterostomy (MSSCU) or ileal conduit (IC). Methods: Patients were divided into two groups according to different BMI change patterns: patients experiencing an elevated postoperative BMI level, along with a clinically significant increase in their BMI (an increase of more than 10%) were categorized as Group 1, while patients experiencing a decrease postoperative BMI level, along with a clinically significant reduction in their BMI (a decrease of more than 5%) were categorized as Group 2. Spearman correlation analysis was used to examine the correlations between quality‐of‐life scores and postoperative clinical parameters. Results: Spearman correlation analysis showed that postoperative BMI, late complications and catheter‐free state were significantly associated with postoperative global QoL and symptom scale in MSSCU and postoperative global QoL and physical scale in IC patients. Additionally, postoperative BMI, catheter‐free state and the use of adjuvant therapy were associated with bad performance in many scales of QoL like body image, future perspective, social scale, future perspective (MSSCU), and abdominal bloating (IC) (Table 2, p<0.05). Patients in Group 2 with significant weight loss had a better Global QoL, a lower rate of stomal stricture and a higher catheter‐free state compared with those in Group 1 in both IC and MSSCU patients. MSSCU patients in Group 2 could achieve a comparable Global QoL as to IC patients in Group 1. Conclusion: Controlling the substantial increase in body weight after surgery contributes to improving QoL, reducing the occurrence of stomal stricture, and ensuring a postoperative catheter‐free state in BCa patients undergoing MSSCU. [ABSTRACT FROM AUTHOR]

Designing highly active, low-cost, and bifunctional oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) catalysts is urgent for the development of metal–air batteries. Herein, by density functional theory (DFT) calculations, we systematically reported a series of dual-metal atom adsorbed novel two-dimensional (2D) MBenes as efficient bifunctional catalysts for the OER/ORR (namely 2TM/TM1TM2–Mo2B2O2, TM = Mn, Fe, Co, Ni). Our theoretical results show that 2Ni–Mo2B2O2, FeCo–Mo2B2O2 and CoNi–Mo2B2O2 exhibit outstanding OER/ORR catalytic activity with overpotentials of 0.49/0.27 V, 0.38/0.50 V and 0.25/0.51 V, respectively, exceeding those of IrO2(110) for the OER and Pt(111) for the ORR. Additionally, these highly active bifunctional catalysts can effectively suppress the hydrogen evolution reaction (HER), ensuring the absolute preference for the OER/ORR. More importantly, the Bader charge (QTM) of adsorbed dual-metal atoms is used as a descriptor of OER/ORR catalytic activity, which is linearly related to ηORR and volcanically related to −ηOER. Our work not only provides new theoretical guidance for developing noble metal-free bifunctional electrocatalysts but also enriches the application of MBenes in electrocatalysis. [ABSTRACT FROM AUTHOR]

Adherence to iron chelation therapy (ICT) is fundamental for preventing iron overload complications and maintaining health-related quality of life (HRQoL) in transfusion-dependent thalassemia (TDT) patients. This study aimed to evaluate adherence, HRQoL, and their association among Malaysian TDT patients. Cross-sectional research was performed among TDT patients aged 18 years and above in Hospital Ampang, Selangor. The adherence and the HRQoL (SF-36) were evaluated using validated instruments. Correlation analyses were carried out to determine the association between ICT adherence and HRQoL. The study recruited 162 patients, with 46.91% (N=76) of respondents reporting being adherent. The mean SF-36 score for TDT patients is 74.58. Remarkably, adherent patients exhibit significantly higher HRQoL (mean SF-36 score 79.21) assessed by the SF-36 questionnaire versus nonadherent patients (mean SF-36 score 69.47) (p=0.00). The findings also revealed a significant positive correlation between female (p=0.032), employed (p=0.003), and age (p=0.050) factors with the patient's HRQoL. The rate of ICT adherence for adult TDT patients is suboptimal and non-adherent to ICT has significantly compromised HRQoL. Enhancing the rate of ICT adherence through interventions such as patient counseling and support programs may lead to enhanced HRQoL outcomes for the TDT population. [ABSTRACT FROM AUTHOR]

Background: This study aimed to comprehensively evaluate the accuracy and effect of computed tomography (CT) and magnetic resonance imaging (MRI) based on artificial intelligence (AI) algorithms for predicting lymph node metastasis in breast cancer patients. Methods: We systematically searched the PubMed, Embase and Cochrane Library databases for literature from inception to June 2023 using keywords that included ‘artificial intelligence’, ‘CT,’ ‘MRI’, ‘breast cancer’ and ‘lymph nodes’. Studies that met the inclusion criteria were screened and their data were extracted for analysis. The main outcome measures included sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve (AUC). Results: A total of 16 studies were included in the final meta-analysis, covering 4,764 breast cancer patients. Among them, 11 studies used the manual algorithm MRI to calculate breast cancer risk, which had a sensitivity of 0.85 (95% confidence interval [CI] 0.79–0.90; p < 0.001; I2 = 75.3%), specificity of 0.81 (95% CI 0.66–0.83; p < 0.001; I2 = 0%), a positive likelihood ratio of 4.6 (95% CI 4.0–4.8), a negative likelihood ratio of 0.18 (95% CI 0.13–0.26) and a diagnostic odds ratio of 25 (95% CI 17–38). Five studies used manual algorithm CT to calculate breast cancer risk, which had a sensitivity of 0.88 (95% CI 0.79–0.94; p < 0.001; I2 = 87.0%), specificity of 0.80 (95% CI 0.69–0.88; p < 0.001; I2 = 91.8%), a positive likelihood ratio of 4.4 (95% CI 2.7–7.0), a negative likelihood ratio of 0.15 (95% CI 0.08–0.27) and a diagnostic odds ratio of 30 (95% CI 12–72). For MRI and CT, the AUC after study pooling was 0.85 (95% CI 0.82–0.88) and 0.91 (95% CI 0.88–0.93), respectively. Conclusion: Computed tomography and MRI images based on an AI algorithm have good diagnostic accuracy in predicting lymph node metastasis in breast cancer patients and have the potential for clinical application. [ABSTRACT FROM AUTHOR]

Epidural administration is the leading therapeutic option for the management of pain associated with lumbar spinal stenosis (LSS), which is characterized by compression of the nerve root due to narrowing of the spinal canal. Corticosteroids are effective in alleviating LSS-related pain but can lead to complications with long-term use. Recent studies have focused on identifying promising medications administered epidurally to affected spinal regions. In this study, we aimed to investigate the effectiveness of harpagoside (HAS) as an epidural medication in rats with LSS. HAS at various concentrations was effective for neuroprotection against ferrous sulfate damage and consequent promotion of axonal outgrowth in primary spinal cord neurons. When two concentrations of HAS (100 and 200 μg/kg) were administered to the rat LSS model via the epidural space once a day for 4 weeks, the inflammatory responses around the silicone block used for LSS were substantially reduced. Consistently, pain-related factors were significantly suppressed by the epidural administration of HAS. The motor functions of rats with LSS significantly improved. These findings suggest that targeted delivery of HAS directly to the affected area via epidural injection holds promise as a potential treatment option for the recovery of patients with LSS. [ABSTRACT FROM AUTHOR]

Objectives: To diagnose the molecular cause of hereditary spastic paraplegia (HSP) observed in a four‐generation family with autosomal dominant inheritance. Methods: Multiplex ligation‐dependent probe amplification (MLPA), whole‐exome sequencing (WES), and RNA sequencing (RNA‐seq) of peripheral blood leukocytes were performed. Reverse transcription polymerase chain reaction (RT‐PCR) and Sanger sequencing were used to characterize target regions of SPAST. Results: A 121‐bp AluYb9 insertion with a 30‐bp poly‐A tail flanked by 15‐bp direct repeats on both sides was identified in the edge of intron 16 in SPAST that segregated with the disease phenotype. Conclusions: We identified an intronic AluYb9 insertion inducing splicing alteration in SPAST causing pure HSP phenotype that was not detected by routine WES analysis. Our findings suggest RNA‐seq is a recommended implementation for undiagnosed cases by first‐line diagnostic approaches. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Ecological interactions among plants, insect herbivores, and parasitoids are pervasive in nature and play important roles in community assembling, but the codiversification of tri‐trophic interactions has received less attention. Here we compare pairwise codiversification patterns between a set of 22 fig species, their herbivorous pollinating and galling wasps, and their parasitoids. The parasitoid phylogeny showed significant congruence and more cospeciation events with host insects phylogeny than with host plants. These results suggest that parasitoid phylogeny and speciation is more closely related to their host insects than to their host plants. The pollinating wasps hosted more parasitoid species than gallers and indicated a more intense interspecific competition among parasitoids associated with pollinators. Closer matching and fewer evolutionary host shifts were found between parasitoids and galler hosts than between parasitoids and pollinator hosts. These results suggest that interspecific competition among parasitoids, rather than resource availability of host wasps, is the main driver of the codiversification pattern in this community. Therefore, our study highlights the important role of interspecific competition among high trophic level insects in plant–insect tri‐trophic community assembling. [ABSTRACT FROM AUTHOR]

Although the recent stereo matching methods based on deep learning achieve unprecedented state-of-the-art performance, the accuracy of these approaches suffers a drastic drop when dealing with environments much different in context from those observed at training time. In this paper, we propose a novel Scene-Aware Network (SA-Net) that integrates scene information to achieve cross-domain stereo matching. Specifically, we design a Scene-Aware Module (SAM) to extract rich scene details, which can make the network with it have better generalization ability between different domain. In order to use rich scene information to perfectly guide shallow features to realize cost aggregation, we introduce a new Multi-element Feature Fusion Strategy (MFFS). Extensive quantitative and qualitative evaluations on different domain illustrate that our SA-Net achieves competitive performance and in particular obtains better ability of domain generalization. [ABSTRACT FROM AUTHOR]

Epidural injection is one of the most common nonsurgical treatment options for long-term pain relief in lumbar spinal stenosis. Recently, various nerve block injections have been used for pain management. Among them, nerve block through epidural injection is a safe and effective method for the clinical treatment of low back or lower extremity pain. Although the epidural injection method has a long history, the effectiveness of long-term epidural injections in disc diseases has not been scientifically proven. In particular, to verify the safety and efficacy of drugs in preclinical studies, the route and method of drug administration in terms of the clinical application method and duration of use must be established. However, there is no standardized method for long-term epidural injections in a rat model of stenosis to identify the precise efficacy and safety of epidural injections. Therefore, standardizing the epidural injection method is very important for evaluating the efficacy and safety of drugs used for back or lower extremity pain. We describe the first standardized long-term epidural injection method for evaluating the efficacy and safety of drugs according to their route of administration in rats with lumbar spinal stenosis. [ABSTRACT FROM AUTHOR]

An electrochemical oxidative approach to spirooxazolidinones from phenol derivatives via intramolecular dearomative amination reactions is developed. This reaction proceeds without metal catalysts and external chemical oxidants, and shows broad substrate scope and diverse functional group compatibility. The synthetic utility of this strategy is further exhibited by the gram‐scale synthesis and late‐stage functionalization. By slightly tunning the reaction conditions, the alcohols (1°, 2° and 3°) can be afforded from phenol derivatives, which is a good strategy for the deprotection of para‐methoxyphenyl (PMP) group to recover the alcohol function. [ABSTRACT FROM AUTHOR]

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen, characterized by its genetic and antigenic variation. The PRRSV vaccine is widely used, however, the unsatisfied heterologic protection and the risk of reverse virulence raise the requirement to find some new anti-PRRSV strategies for disease control. Tylvalosin tartrate is used to inhibit PRRSV in the field non-specifically, however, the mechanism is still less known. Methods: The antiviral effects of Tylvalosin tartrates from three producers were evaluated in a cell inoculation model. Their safety and efficacy concentrations, and effecting stage during PRRSV infection were analyzed. And, the Tylvalosin tartrates regulated genes and pathways which are potentially related to the anti-viral effect were further explored by using transcriptomics analysis. Last, the transcription level of six anti-virus-related DEGs was selected to confirm by qPCR, and the expression level of HMOX1, a reported anti-PRRSV gene, was proved by western blot. Results: The safety concentrations of Tylvalosin tartrates from three different producers were 40 µg/mL (Tyl A, Tyl B, and Tyl C) in MARC-145 cells and 20 µg/mL (Tyl A) or 40 µg/mL (Tyl B and Tyl C) in primary pulmonary alveolar macrophages (PAMs) respectively. Tylvalosin tartrate can inhibit PRRSV proliferation in a dose-dependent manner, causing more than 90% proliferation reduction at 40 µg/mL. But it shows no virucidal effect, and only achieves the antiviral effect via long-term action on the cells during the PRRSV proliferation. Furthermore, GO terms and KEGG pathway analysis was carried out based on the RNA sequencing and transcriptomic data. It was found that the Tylvalosin tartrates can regulate the signal transduction, proteolysis, and oxidation-reduction process, as well as some pathways such as protein digestion and absorption, PI3K-Akt signaling, FoxO signaling, and Ferroptosis pathways, which might relate to PRRSV proliferation or host innate immune response, but further studies still need to confirm it. Among them, six antivirus-related genes HMOX1, ATF3, FTH1, FTL, NR4A1, and CDKN1A were identified to be regulated by Tylvalosin tartrate, and the increased expression level of HMOX1 was further confirmed by western blot. Conclusions: Tylvalosin tartrate can inhibit PRRSV proliferation in vitro in a dose-dependent manner. The identified DEGs and pathways in transcriptomic data will provide valuable clues for further exploring the host cell restriction factors or anti-PRRSV target. [ABSTRACT FROM AUTHOR]