Who holds the social power? The development of children's social power perceptions in China.

This study examined the development of social power perceptions among Chinese children aged 3-5 years (N = 105). After watching videos about various social power cues, such as resource possession, resource control, goal achievement, permission, giving orders, setting norms and popularity, the children were asked to identify the powerful agents (whom do you believe is the more powerful person?) in the videos and provide explanations (why do you think he (she) is a powerful person?). Three-year-olds can recognize powerful agents who can grant 'permission' to other agents. By the age of 4, children begin to associate 'popularity', 'resource possession' and 'goal achievement' with social power. Five-year olds demonstrated the ability to recognize agents who control resources as being more powerful. Analysis of the reasons the children provided for their judgements revealed that for almost every cue (except giving orders), more than 14% of the responses highlighted 'possession of material resources' as an indicator of power. For children aged 3-5 years, 'resource possession' cues may be their preferred basis for inferring and explaining power differences. These results would facilitate researchers to further unravel the mechanisms underlying the development of children's social power perceptions.

Development and validation of a nomogram integrating marital status for 5-year overall survival of chondrosarcoma: a population-based study.

OBJECTIVES: The objective of this study was to evaluate the influence of marital status on overall survival (OS) and develop a nomogram for predicting 5-year OS in chondrosarcoma (CHS) patients. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify CHS patients diagnosed between 2010 and 2018. Survival rates were calculated using Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analyses. An independent cohort was used for external validation of the nomogram. Performance evaluation of the nomogram was conducted using Harrell's concordance index (C-index), calibration plot, and decision curve analysis (DCA). RESULTS: In the SEER cohort, Kaplan-Meier analysis showed significant differences in OS among CHS patients with different marital statuses (P < 0.001), with widowed patients having the lowest OS. In terms of gender, there were significant survival differences based on marital status in females (P < 0.001), but not in males (P = 0.067). The OS of married and single females is significantly higher than that of married (P < 0.001) and single male (P = 0.006), respectively. Kaplan-Meier curves showed no significant difference in OS between groups stratified by either gender or marital status in the external cohort. Univariate and multivariate analyses confirmed that age at diagnosis, gender, marital status, tumor size, histological type, tumor grade, SEER stage, and surgery were independent prognostic factors for OS. The nomogram demonstrated high internal and external validation C-indexes of 0.818 and 0.88, respectively. Calibration plots, DCA curve, and Kaplan-Meier curve (P < 0.001) confirmed the excellent performance and clinical utility of the nomogram. CONCLUSIONS: Marital status was an independent factor influencing OS in CHS patients, with widowed patients having the worst prognosis. The OS of both married and single females is significantly higher than that of their male counterparts. However, these findings require further validation in a large independent cohort. While the contribution of marital status on predicting OS appears modest, our nomogram accurately predicted 5-year OS and identified high-risk groups, providing a valuable tool for clinical decision-making.

Electrically tunable virtual image Luneburg lens using graphene.

Virtual image lenses play essential roles in various optical devices and applications, including vision correction, photography, and scientific instruments. Here, we introduce an approach for creating virtual image Luneburg lenses (LL) on graphene. Remarkably, the graphene plasmonic lens (GPL) exhibits electrically tunable virtual focusing capabilities. The design principle of the tunability is based on the nonlinear relationship between surface plasmon polariton (SPP) wave mode index and chemical potential of graphene. By controlling the gate voltage of graphene, we can achieve continuous tuning of virtual focus. A ray-tracing technique is employed to determine the required gate voltages for various virtual focal lengths. The proposed GPL facilitates adjustable virtual focusing, promising advancements in highly adaptive and transformative nanophotonic devices.

Effect of fluorine on the photovoltaic properties of 2,1,3-benzothiadiazole-based alternating conjugated polymers by changing the position and number of fluorine atoms.

Fluorination is one of the most effective ways to manipulate molecular packing, optical bandgap and molecular energy levels in organic semiconductor materials. In this work, different number of fluorine atoms was introduced into the acceptor moiety 2,2'-dithiophene linked 2,1,3-benzothiadiazole, utilizing the alkylthiophene modified dithieno[2,3-d:2',3'-d']benzo[1,2-b:4,5-b] (DTBDT) as the donor unit, three polymers: PDTBDT-0F-BTs, PDTBDT-2F-BTs and PDTBDT-6F-FBTs were synthesized. With the number of fluorine atoms in each repeat unit of polymers varying from 0 to 2 and then up to 6, PDTBDT-0F-BTs, PDTBDT-2F-BTs and PDTBDT-6F-FBTs exhibited gradually downshifted energy levels and improved dielectric constants (εr) from 3.4 to 4.3 to 5.8, further successively increased charge transport mobilities. As a result, the power conversion efficiency (PCE) of the bulk heterojunction organic photovoltaic devices (BHJ-OPV) from the blend films of aforementioned polymers paired with PC71BM were gradually increased from 1.69 for PDTBDT-0F-BTs to 1.89 for PDTBDT-2F-BTs and then to 5.28 for PDTBDT-6F-FBTs. The results show that the continuous insertion of fluorine atoms into the repeating units of the benzothiadiazole conjugated polymer leads to the deepening of HOMO energy level, the increase of εr and the increase of charge mobility, which improve the efficiency of charge transfer and electron collection, thus improving the photovoltaic performance of BHJ-OPV.

Can irisin be developed as the molecular evolutionary clock based on the origin and functions?

Irisin, a myokine identified in 2012, has garnered research interest for its capacity to induce browning of adipocytes and improve metabolic parameters. As such, the potential therapeutic applications of this exercise-induced peptide continue to be explored. Though present across diverse animal species, sequence analysis has revealed subtle variation in the irisin protein. In this review, we consider the effects of irisin on disease states in light of its molecular evolution. We summarize current evidence for irisin's influence on pathologies and discuss how sequence changes may inform development of irisin-based therapies. Furthermore, we propose that the phylogenetic variations in irisin could potentially be leveraged as a molecular clock to elucidate evolutionary relationships.

Spatial reconstructed local attention Res2Net with F0 subband for fake speech detection.

The rhythm of bonafide speech is often difficult to replicate, which causes that the fundamental frequency (F0) of synthetic speech is significantly different from that of real speech. It is expected that the F0 feature contains the discriminative information for the fake speech detection (FSD) task. In this paper, we propose a novel F0 subband for FSD. In addition, to effectively model the F0 subband so as to improve the performance of FSD, the spatial reconstructed local attention Res2Net (SR-LA Res2Net) is proposed. Specifically, Res2Net is used as a backbone network to obtain multiscale information, and enhanced with a spatial reconstruction mechanism to avoid losing important information when the channel group is constantly superimposed. In addition, local attention is designed to make the model focus on the local information of the F0 subband. Experimental results on the ASVspoof 2019 LA dataset show that our proposed method obtains an equal error rate (EER) of 0.47% and a minimum tandem detection cost function (min t-DCF) of 0.0159, achieving the state-of-the-art performance among all of the single systems.

In situ one step growth of amorphous tin oxide electron transport layer for high-performance perovskite solar cells.

Tin oxide used in electron transport layer (ETL) exhibits key role in transmitting electrons and blocking holes in perovskite solar cells (PSCs) device. However, crystal tin oxide nanoparticles (NPs) become necessary to form SnO2 film by method of spin-coating, resulting in possible surface defect and cracks among SnO2 NPs, corresponding to unsatisfied performance PSCs. Herein, an amorphous tin oxide thin film is creatively in situ grew onto Fluorine-doped Tin Oxide (FTO) substrate as ETL. The designed solar cell device with structure of FTO/SnO2/MAPbI3/Sprio-OMeTAD/Ag owns a champion photoelectric conversion efficiency (PCE) up to 17.64%, 76.20% of filling coefficient (FF), and 1.09 V of open-circuit voltage (Voc), in comparing with 16.43%, 64.35% and 1.05 V for control group (crystal tin oxide as ETL), respectively. Besides, the champion device keeps 83.33% of initial PCE under nitrogen (N2) condition for one month, in comparison with 76.09% for control group. This work provides a viable strategy for facile preparing amorphous tin oxide film based ETL in perovskite solar cells.

KAT7 enhances the proliferation and metastasis of head and neck squamous carcinoma by promoting the acetylation level of LDHA.

Lysine acetyltransferase 7 (KAT7), a histone acetyltransferase, has recently been identified as an oncoprotein and has been implicated in the development of various malignancies. However, its specific role in head and neck squamous carcinoma (HNSCC) has not been fully elucidated. Our study revealed that high expression of KAT7 in HNSCC patients is associated with poor survival prognosis and silencing KAT7 inhibits the Warburg effect, leading to reduced proliferation, invasion, and metastatic potential of HNSCC. Further investigation uncovered a link between the high expression of KAT7 in HNSCC and tumor-specific glycolytic metabolism. Notably, KAT7 positively regulates Lactate dehydrogenase A (LDHA), a key enzyme in metabolism, to promote lactate production and create a conducive environment for tumor proliferation and metastasis. Additionally, KAT7 enhances LDHA activity and upregulates LDHA protein expression by acetylating the lysine 118 site of LDHA. Treatment with WM3835, a KAT7 inhibitor, effectively suppressed the growth of subcutaneously implanted HNSCC cells in mice. In conclusion, our findings suggest that KAT7 exerts pro-cancer effects in HNSCC by acetylating LDHA and may serve as a potential therapeutic target. Inhibiting KAT7 or LDHA expression holds promise as a therapeutic strategy to suppress the growth and progression of HNSCC.

Bearing Fault Diagnosis via Stepwise Sparse Regularization with an Adaptive Sparse Dictionary.

Vibration monitoring is one of the most effective approaches for bearing fault diagnosis. Within this category of techniques, sparsity constraint-based regularization has received considerable attention for its capability to accurately extract repetitive transients from noisy vibration signals. The optimal solution of a sparse regularization problem is determined by the regularization term and the data fitting term in the cost function according to their weights, so a tradeoff between sparsity and data fidelity has to be made inevitably, which restricts conventional regularization methods from maintaining strong sparsity-promoting capability and high fitting accuracy at the same time. To address the limitation, a stepwise sparse regularization (SSR) method with an adaptive sparse dictionary is proposed. In this method, the bearing fault diagnosis is modeled as a multi-parameter optimization problem, including time indexes of the sparse dictionary and sparse coefficients. Firstly, sparsity-enhanced optimization is conducted by amplifying the regularization parameter, making the time indexes and the number of atoms adaptively converge to the moments when impulses occur and the number of impulses, respectively. Then, fidelity-enhanced optimization is carried out by removing the regularization term, thereby obtaining the high-precision reconstruction amplitudes. Simulations and experiments verify that the reconstruction accuracy of the SSR method outperforms other sparse regularization methods under most noise conditions, and thus the proposed method can provide more accurate results for bearing fault diagnosis.

pH-responsive size-adjustable liposomes induce apoptosis of fibroblasts and macrophages for rheumatoid arthritis treatment.

In rheumatoid arthritis (RA), macrophages infiltrate joints, while fibroblast-like synovial cells proliferate abnormally, forming a barrier against drug delivery, which hinders effective drug delivery to joint focus. Here we firstly designed a pH-responsive size-adjustable nanoparticle, composed by methotrexate (MTX)-human serum albumin (HSA) complex coating with pH-responsive liposome (Lipo/MTX-HSA) for delivering drugs specifically to inflamed joints in acidic environments. We showed in vitro that the nanoparticles can induce mitochondrial dysfunction, promote apoptosis of fibroblast-like synoviocytes and macrophages, further reduce the secretion of inflammatory factors (TNF-α, IL-1ß, MMP-9), and regulate the inflammatory microenvironment. We also demonstrated similar effects in a rat model of arthritis, in which Lipo/MTX-HSA accumulated in arthritic joints, and at low pH, liposome phospholipid bilayer cleavage released small-sized MTX-HSA, which effectively reduced the number of fibroblast-synoviocytes and macrophages in joints, alleviated joint inflammation, and repaired bone erosion. These findings suggest that microenvironment-responsive size-adjustable nanoparticles show promise as a treatment against rheumatoid arthritis. STATEMENT OF SIGNIFICANCE: Abnormal proliferation of fibroblast synoviocytes poses a physical barrier to effective nanoparticle delivery. We designed size-adjustable nano-delivery systems by preparing liposomes with cholesterol hemisuccinate (CHEM), which were subsequently loaded with small-sized albumin nanoparticles encapsulating the cytotoxic drug MTX (MTX-HSA), termed Lipo/MTX-HSA. Upon tail vein injection, Lipo/MTX-HSA could be aggregated at the site of inflammation via the ELVIS effect in the inflamed joint microenvironment. Specifically, intracellular acidic pH-triggered dissociation of liposomes promoted the release of MTX-HSA, which was further targeted to fibroblasts or across fibroblasts to macrophages to exert anti-inflammatory effects. The results showed that liposomes with adjustable particle size achieved efficient drug delivery, penetration and retention in joint sites; the strategy exerted significant anti-inflammatory effects in the treatment of rheumatoid arthritis by inducing mitochondrial dysfunction to promote apoptosis in fibrosynoviocytes and macrophages.

Nickel-catalyzed acylation of vinylpyridine with alkylzincs under 1 atm CO.

A nickel-catalyzed acylation of vinylpyridines with CO at atmospheric pressure is reported, allowing for an expedient approach to synthesize ß-acyl pyridine derivatives with high regio- and chemoselectivity. The electron-withdrawing property of pyridine plays pivotal roles in activating the alkenyl group, thereby facilitating this carbonylative process. In addition to vinylpyridines, other alkenylheterocycles such as thiazole and quinoline were also suitable for this method.

Risk Factors of Hidden Blood Loss in Unilateral Biportal Endoscopic Surgery for Patients with Lumbar Spinal Stenosis.

OBJECTIVE: Unilateral biportal endoscopic (UBE) surgery has recently been used as a minimally invasive procedure for the treatment of lumbar spinal stenosis and is associated with less perioperative blood loss. However, perioperative hidden blood loss (HBL) may be neglected during UBE. This study aimed to examine the volume of HBL and discuss the influential risk factors for HBL during unilateral biportal endoscopic surgery. METHODS: From January 2022 to August 2022, 51 patients underwent percutaneous unilateral biportal endoscopic surgery for lumbar spinal stenosis at the Department of Spinal Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and were enrolled in this study. The data included general indicators (age, sex and body mass index [BMI]), underlying disease (hypertension and diabetes), laboratory test results (prothrombin time [PT], activated partial thromboplastin time [APTT], fibrinogen [Fbg]), and preoperative and postoperative hematocrit and hemoglobin), related imaging parameters (severity of intervertebral disc [IVD] degeneration and soft tissue thickness of the interlaminar approach), number of operated vertebrae and operation time. Total blood loss (TBL) and HBL during surgical procedures were measured via the Gross formula. Influential factors were further analyzed by multivariate linear regression analysis and t-tests. RESULTS: The mean HBL was 257.89 ± 190.66 mL for single-operation patients and 296.58 ± 269.75 mL for two-operation patients. Patients with lower PT (p = 0.044), deeper tissue thickness (p = 0.047), and diabetes mellitus were determined to have more HBL during UBE. The operation time might also be an important factor (p = 0.047). However, sex (p = 0.265), age (p = 0.771/0.624), BMI (p = 0.655/0.664), APTT (p = 0.545/0.751), degree of degenerated IVD (p = 0.932/0.477), and hypertension (p = 0.356/0.896) were not related to HBL. CONCLUSION: This study determined the different influential factors of HBL during UBE. PT, tissue thickness, and diabetes mellitus are the independent risk factors that affect HBL incidence. Long PT may decrease the volume of HBL within a certain range. Tissue thickness and diabetes mellitus can lead to an increased volume of HBL.

Comparison of different criteria for estimating major pathological response in resectable non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy.

BACKGROUND: Major pathological response (MPR) is proposed as a surrogate endpoint for survival in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. However, the criteria for estimating MPR differ between the recommendations of the International Association for the Study of Lung Cancer (IASLC) and the immune-related pathologic response criterion (irPRC). IASLC's criteria focus solely on evaluating the primary tumor, while irPRC's criteria encompass both the primary tumor and lymph node metastasis. Our objective is to compare the prognostic value of different criteria for estimating MPR. METHODS: We conducted a retrospective study on a cohort of 235 patients with NSCLC after neoadjuvant chemoimmunotherapy. The survival endpoint was event-free survival (EFS). The MPR status of each patient was evaluated using both IASLC's criteria and irPRC's criteria. The prognostic value was compared using the Area Under Curve (AUC). RESULTS: The MPR rates were 63.4 % (149/235) and 57.4 % (135/235) according to IASLC's and irPRC's criteria, respectively. Inconsistent cases, characterized by MPR status according to IASLC's criteria but non-MPR status according to irPRC's criteria, constituted 6.0 % (14/235) of the overall cohort and 15.2 % (14/92) of patients with pretreatment N positive disease. Interestingly, all inconsistent patients showed no recurrence during the study period. Although both MPR statuses according to IASLC (p = 0.00039) and irPRC (p = 0.0094) were associated with improved EFS, IASLC's criteria (AUC = 0.65) were superior to irPRC's criteria (AUC = 0.62) with a higher AUC value. CONCLUSION: IASLC's criteria for estimating MPR were superior to irPRC's criteria in predicting EFS for NSCLC after neoadjuvant chemoimmunotherapy.

Microplastics: A potential proxy for tracing extreme flood events in estuarine environments.

The transport of microplastics (MPs) is susceptible to being influenced by catchment hydrology; however, there is a notable lack of research on their retention and responses to flood events in estuarine sedimentary records. Herein, we collected two cores in the Yangtze Estuary to explore their microplastic pollution, influencing factors and linkage to flood events. MP abundance exhibited a decreasing trend from the top to the bottom in both cores. Both plastic production and sediment mean grain size showed a significant positive correlation with MP abundance. The sedimentary record displayed a marked surge in MP abundance during the extreme flood period, suggesting a direct influence of flooding on MP deposition. The resuspension of upstream MPs and erosion of land-based MPs by heavy rain might be responsible for this increase. Furthermore, our study identified significant periodicities in MP abundance, closely aligned with the hydrological patterns of the Yangtze River. This study highlights the role of floods in fluvial MP distribution and proposes MPs as a proxy of extreme floods from the 20th century in estuarine environments.

Cooperative Cu/azodiformate system-catalyzed allylic C-H amination of unactivated internal alkenes directed by aminoquinoline.

Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp3)-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp3)-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity.

SPOCK2 modulates neuropathic pain by interacting with MT1-MMP to regulate astrocytic MMP-2 activation in rats with chronic constriction injury.

BACKGROUND: Neuropathic pain (NP) is a kind of intractable pain. The pathogenesis of NP remains a complicated issue for pain management practitioners. SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (SPOCK2) are members of the SPOCK family that play a significant role in the development of the central nervous system. In this study, we investigated the role of SPOCK2 in the development of NP in a rat model of chronic constriction injury (CCI). METHODS: Sprague-Dawley rats were randomly grouped to establish CCI models. We examined the effects of SPOCK2 on pain hpersensitivity and spinal astrocyte activation after CCI-induced NP. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to reflects the pain behavioral degree. Molecular mechanisms involved in SPOCK2-mediated NP in vivo were examined by western blot analysis, immunofluorescence, immunohistochemistry, and co-immunoprecipitation. In addition, we examined the SPOCK2-mediated potential protein-protein interaction (PPI) in vitro coimmunoprecipitation (Co-IP) experiments. RESULTS: We founded the expression level of SPOCK2 in rat spinal cord was markedly increased after CCI-induced NP, while SPOCK2 downregulation could partially relieve pain caused by CCI. Our research showed that SPOCK2 expressed significantly increase in spinal astrocytes when CCI-induced NP. In addition, SPOCK2 could act as an upstream signaling molecule to regulate the activation of matrix metalloproteinase-2 (MMP-2), thus affecting astrocytic ERK1/2 activation and interleukin (IL)-1ß production in the development of NP. Moreover, in vitro coimmunoprecipitation (Co-IP) experiments showed that SPOCK2 could interact with membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP14) to regulate MMP-2 activation by the SPARC extracellular (SPARC_EC) domain. CONCLUSIONS: Research shows that SPOCK2 can interact with MT1-MMP to regulate MMP-2 activation, thus affecting astrocytic ERK1/2 activation and IL-1ß production to achieve positive promotion of NP.

Rapid and Accurate Quantification of Viable Lactobacillus Cells in Infant Formula by Flow Cytometry Combined with Propidium Monoazide and Signal-Enhanced Fluorescence In Situ Hybridization.

Lactobacillus is an important member of the probiotic bacterial family for regulating human intestinal microflora and preserving its normalcy, and it has been widely used in infant formula. An appropriate and feasible method to quantify viable Lactobacilli cells is urgently required to evaluate the quality of probiotic-fortified infant formula. This study presents a rapid and accurate method to count viable Lactobacilli cells in infant formula using flow cytometry (FCM). First, Lactobacillus cells were specifically and rapidly stained by oligonucleotide probes based on a signal-enhanced fluorescence in situ hybridization (SEFISH) technique. A DNA-binding fluorescent probe, propidium monoazide (PMA), was then used to accurately recognize viable Lactobacillus cells. The entire process of this newly developed PMA-SEFISH-FCM method was accomplished within 2.5 h, which included pretreatment, dual staining, and FCM analysis; thus, this method showed considerably shorter time-to-results than other rapid methods. This method also demonstrated a good linear correlation (R2 = 0.9994) with the traditional plate-based method with a bacterial recovery rate of 91.24%. To the best of our knowledge, the present study is the first report of FCM combined with PMA and FISH for the specific detection of viable bacterial cells.

3D-printed PCL@BG scaffold integrated with SDF-1α-loaded hydrogel for enhancing local treatment of bone defects.

BACKGROUND: The long-term nonunion of bone defects is always a difficult problem in orthopaedics treatment. Artificial bone implants made of polymeric materials are expected to solve this problem due to their suitable degradation rate and good biocompatibility. However, the lack of mechanical strength, low osteogenic induction ability and poor hydrophilicity of these synthetic polymeric materials limit their large-scale clinical application. RESULTS: In this study, we used bioactive glass (BG) (20%, W/W) and polycaprolactone (PCL, 80%, W/W) as raw materials to prepare a bone repair scaffold (PCL@BG20) using fused deposition modelling (FDM) three-dimensional (3D) printing technology. Subsequently, stromal cell-derived factor-1α (SDF-1α) chemokines were loaded into the PCL@BG20 scaffold pores with gelatine methacryloyl (GelMA) hydrogel. The experimental results showed that the prepared scaffold had a porous biomimetic structure mimicking that of cancellous bone, and the compressive strength (44.89 ± 3.45 MPa) of the scaffold was similar to that of cancellous bone. Transwell experiments showed that scaffolds loaded with SDF-1α could promote the recruitment of bone marrow stromal cells (BMSCs). In vivo data showed that treatment with scaffolds containing SDF-1α and BG (PCL@BG-GelMA/SDF-1α) had the best effect on bone defect repair compared to the other groups, with a large amount of new bone and mature collagen forming at the bone defect site. No significant organ toxicity or inflammatory reactions were observed in any of the experimental groups. CONCLUSIONS: The results show that this kind of scaffold containing BG and SDF-1α serves the dual functions of recruiting stem cell migration in vivo and promoting bone repair in situ. We envision that this scaffold may become a new strategy for the clinical treatment of bone defects.

PiRNA hsa_piR_019949 promotes chondrocyte anabolic metabolism by inhibiting the expression of lncRNA NEAT1.

BACKGROUND: Osteoarthritis is a prevalent degenerative joint condition typically found in individuals who are aged 50 years or older. In this study, the focus is on PIWI-interacting RNA (piRNA), which belongs to a category of small non-coding RNAs. These piRNAs play a role in the regulation of gene expression and the preservation of genomic stability. The main objective of this research is to examine the expression of a specific piRNA called hsa_piR_019949 in individuals with osteoarthritis, to understand its impact on chondrocyte metabolism within this condition. METHODS: We analyzed piRNA expression in osteoarthritis cartilage using the GEO database. To understand the impact of inflammatory factors on piRNA expression in chondrocytes, we conducted RT-qPCR experiments. We also investigated the effect of piRNA hsa_piR_019949 on chondrocyte proliferation using CCK-8 and clone formation assays. Furthermore, we assessed the influence of piRNA hsa_piR_019949 on chondrocyte apoptosis by conducting flow cytometry analysis. Additionally, we examined the differences in cartilage matrix composition through safranine O staining and explored the downstream regulatory mechanisms of piRNA using transcriptome sequencing. Lentiviral transfection of NEAT1 and NLRP3 was performed to regulate the metabolism of chondrocytes. RESULTS: Using RNA sequencing technology, we compared the gene expression profiles of 5 patients with osteoarthritis to 3 normal controls. We found a gene called hsa_piR_019949 that showed differential expression between the two groups. Specifically, hsa_piR_019949 was downregulated in chondrocytes when stimulated by IL-1ß, an inflammatory molecule. In further investigations, we discovered that overexpression of hsa_piR_019949 in vitro led to increased proliferation and synthesis of the extracellular matrix in chondrocytes, which are cells responsible for cartilage formation. Conversely, suppressing hsa_piR_019949 expression resulted in increased apoptosis (cell death) and degradation of the extracellular matrix in chondrocytes. Additionally, we found that the NOD-like receptor signaling pathway is linked to the low expression of hsa_piR_019949 in a specific chondrocyte cell line called C28/I2. Furthermore, we observed that hsa_piR_019949 can inhibit the expression of a long non-coding RNA called NEAT1 in chondrocytes. We hypothesize that NEAT1 may serve as a downstream target gene regulated by hsa_piR_019949, potentially influencing chondrocyte metabolism and function in the context of osteoarthritis. CONCLUSIONS: PiRNA hsa_piR_019949 has shown potential in promoting the proliferation of chondrocytes and facilitating the synthesis of extracellular matrix in individuals with osteoarthritis. This is achieved by inhibiting the expression of a long non-coding RNA called NEAT1. The implication is that by using hsa_piR_019949 mimics, which are synthetic versions of the piRNA, as a therapeutic approach, it may be possible to effectively treat osteoarthritis.

Enhancing Nigrosome-1 Sign Identification via Interpretable AI using True Susceptibility Weighted Imaging.

BACKGROUND: Nigrosome 1 (N1), the largest nigrosome region in the ventrolateral area of the substantia nigra pars compacta, is identifiable by the "N1 sign" in long echo time gradient echo MRI. The N1 sign's absence is a vital Parkinson's disease (PD) diagnostic marker. However, it is challenging to visualize and assess the N1 sign in clinical practice. PURPOSE: To automatically detect the presence or absence of the N1 sign from true susceptibility weighted imaging by using deep-learning method. STUDY TYPE: Prospective. POPULATION/SUBJECTS: 453 subjects, including 225 PD patients, 120 healthy controls (HCs), and 108 patients with other movement disorders, were prospectively recruited including 227 males and 226 females. They were divided into training, validation, and test cohorts of 289, 73, and 91 cases, respectively. FIELD STRENGTH/SEQUENCE: 3D gradient echo SWI sequence at 3T; 3D multiecho strategically acquired gradient echo imaging at 3T; NM-sensitive 3D gradient echo sequence with MTC pulse at 3T. ASSESSMENT: A neuroradiologist with 5 years of experience manually delineated substantia nigra regions. Two raters with 2 and 36 years of experience assessed the N1 sign on true susceptibility weighted imaging (tSWI), QSM with high-pass filter, and magnitude data combined with MTC data. We proposed NINet, a neural model, for automatic N1 sign identification in tSWI images. STATISTICAL TESTS: We compared the performance of NINet to the subjective reference standard using Receiver Operating Characteristic analyses, and a decision curve analysis assessed identification accuracy. RESULTS: NINet achieved an area under the curve (AUC) of 0.87 (CI: 0.76-0.89) in N1 sign identification, surpassing other models and neuroradiologists. NINet localized the putative N1 sign within tSWI images with 67.3% accuracy. DATA CONCLUSION: Our proposed NINet model's capability to determine the presence or absence of the N1 sign, along with its localization, holds promise for enhancing diagnostic accuracy when evaluating PD using MR images. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.