Noncoding SNP at rs1663689 represses ADGRG6 via interchromosomal interaction and reduces lung cancer progression.

A previous genome-wide association study (GWAS) revealed an association of the noncoding SNP rs1663689 with susceptibility to lung cancer in the Chinese population. However, the underlying mechanism is unknown. In this study, using allele-specific 4C-seq in heterozygous lung cancer cells combined with epigenetic information from CRISPR/Cas9-edited cell lines, we show that the rs1663689 C/C variant represses the expression of ADGRG6, a gene located on a separate chromosome, through an interchromosomal interaction of the rs1663689 bearing region with the ADGRG6 promoter. This reduces downstream cAMP-PKA signaling and subsequently tumor growth both in vitro and in xenograft models. Using patient-derived organoids, we show that rs1663689 T/T-but not C/C-bearing lung tumors are sensitive to the PKA inhibitor H89, potentially informing therapeutic strategies. Our study identifies a genetic variant-mediated interchromosomal interaction underlying ADGRG6 regulation and suggests that targeting the cAMP-PKA signaling pathway may be beneficial in lung cancer patients bearing the homozygous risk genotype at rs1663689.

Molecular features and evolutionary trajectory of ASCL1+ and NEUROD1+ SCLC cells.

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer without recognised morphologic or genetic heterogeneity. Based on the expression of four transcription factors, ASCL1, NEUROD1, POU2F3, and YAP1, SCLCs are classified into four subtypes. However, biological functions of these different subtypes are largely uncharacterised. METHODS: We studied intratumoural heterogeneity of resected human primary SCLC tissues using single-cell RNA-Seq. In addition, we undertook a series of in vitro and in vivo functional studies to reveal the distinct features of SCLC subtypes. RESULTS: We identify the coexistence of ASCL1+ and NEUROD1+ SCLC cells within the same human primary SCLC tissue. Compared with ASCL1+ SCLC cells, NEUROD1+ SCLC cells show reduced epithelial features and lack EPCAM expression. Thus, EPCAM can be considered as a cell surface marker to distinguish ASCL1+ SCLC cells from NEUROD1+ SCLC cells. We further demonstrate that NEUROD1+ SCLC cells exhibit higher metastatic capability than ASCL1+ SCLC cells and can be derived from ASCL1+ SCLC cells. CONCLUSIONS: Our studies unveil the biology and evolutionary trajectory of ASCL1+ and NEUROD1+ SCLC cells, shedding light on SCLC tumourigenesis and progression.

Lactic acid bacteria in relieving constipation: mechanism, clinical application, challenge, and opportunity.

Constipation is a prevalent gastrointestinal symptom that can considerably affect a patients' quality of life. Although several drugs have been used to treat constipation, they are associated with high costs, side effects, and low universality. Therefore, alternative intervention strategies are urgently needed. Traditional lactic acid bacteria (LAB), such as Bifidobacterium and Lactobacillus, play a vital role in regulating intestinal microecology and have demonstrated favorable effects in constipation; however, a comprehensive review of their constipation relief mechanisms is limited. This review summarizes the pathogenesis of constipation and the relationship between intestinal motility and gut microbiota, elucidates the possible mechanism by which LAB alleviates of constipation through a systematic summary of animal and clinical research, and highlights the challenges and applications of LAB in the treatment of constipation. Our review can improve our understanding of constipation, and advance targeted microecological therapeutic agents, such as LAB.

Associations Between Family Function and Non-suicidal Self-injury Among Chinese Urban Adolescents with and Without Parental Migration.

The study aims to explore the effect of family function on non-suicidal self-injury (NSSI) among Chinese urban adolescents with and without parental migration. Between April 21st to May 12th, 2021, adolescents were recruited from Shenzhen city of Guangdong province, China (n = 124,357). Of all the participants, 22,855 (18.4%) were left-behind children (LBC). Family function, NSSI, depression, and socio-demographic characteristics were assessed using a series of self-reported questionnaires. Urban LBC had a higher NSSI frequency, while a lower level of family function than non-LBC. After controlling for confounders, parental migration was significantly associated with NSSI, and family dysfunction was a robust risk factor for NSSI as well. The protective effect of family function on NSSI of LBC was stronger than non-LBC. This implies that children with higher levels of family function tend to exhibit a lower frequency of NSSI, especially in those with parental migration. In practice, adolescents' NSSI prevention and intervention strategies should focus on improving family function.

Diazabicyclic Electroactive Ionenes for Efficient and Stable Organic Solar Cells.

Electroactive ionenes combining caged-shaped diazabicyclic cations and aromatic diimides were developed as interlayers in organic solar cells (OSCs). These ionenes reduce the work-function of air-stable metal electrodes (e.g., Ag, Cu and Au) by generating strong interfacial dipoles, and their optoelectronic and morphological characters can be modulated by aromatic diimides, leading to high conductivity and good compatibility with active layers. The optimal ionene exhibits superior charge-transport, desirable crystallinity, and weak visible-absorption, boosting the efficiency of benchmark PM6 : Y6-based OSCs up to 17.44 %. The corresponding normal devices show excellent stability at maximum power point test under one sun illumination for 1000 h. Replacing Y6 with L8-BO promotes the efficiency to 18.43 %, one of the highest in binary OSCs. Notably, high efficiencies >16 % are maintained as the interlayer thickness increasing to 105 nm, the best result with interlayer-thickness over 100 nm.

Source localization in the deep ocean using a convolutional neural network.

In deep-sea source localization, some of the existing methods only estimate the source range, while the others produce large errors in distance estimation when estimating both the range and depth. Here, a convolutional neural network-based method with high accuracy is introduced, in which the source localization problem is solved as a regression problem. The proposed neural network is trained by a normalized acoustic matrix and used to predict the source position. Experimental data from the western Pacific indicate that this method performs satisfactorily: the mean absolute percentage error of the range is 2.10%, while that of the depth is 3.08%.

Room-Temperature Phosphorescence Invoked Through Norbornyl-Driven Intermolecular Interaction Intensification with Anomalous Reversible Solid-State Photochromism.

Herein, norbornyl (NB), a bulky annular nonconjugated spacer, is melded into π systems to construct two groups of ladder-type room-temperature phosphorescence (RTP) luminogens. The effect of the NB on π-π interactions, packing modes and RTP performance is explored systematically. The experimental and computational results demonstrate the versatility of NB in reducing π-π distances and synergistically intensifying the intermolecular interactions, which not only induces intersystem crossing from S1 to Tn but also diminishes the nonradiative decay of triplet excitons. Impressively, 1800-fold phosphorescence lifetime enhancement is achieved in comparison with the reference compounds without NB. The molecular packing and RTP performance can be further modulated by the length of the backbones and terminal end-groups. It is quite peculiar that NB-annulated phthalic acid exhibits reversible photochromism in the solid state, likely due to the formation of persistent radical pairs. Our study paves an ingenious avenue towards enhancing intermolecular interactions and provides significant implications for a better comprehensive understanding of the origin of their RTP and the inherent photophysical mechanism.

Analyzing the regulation of miRNAs on protein-protein interaction network in Hodgkin lymphoma.

BACKGROUND: Hodgkin Lymphoma (HL) is a type of aggressive malignancy in lymphoma that has high incidence in young adults and elderly patients. Identification of reliable diagnostic markers and efficient therapeutic targets are especially important for the diagnosis and treatment of HL. Although many HL-related molecules have been identified, our understanding on the molecular mechanisms underlying the disease is still far from complete due to its complex and heterogeneous characteristics. In such situation, exploring the molecular mechanisms underlying HL via systems biology approaches provides a promising option. In this study, we try to elucidate the molecular mechanisms related to the disease and identify potential pharmaceutical targets from a network-based perspective. RESULTS: We constructed a series of network models. Based on the analysis of these networks, we attempted to identify the biomarkers and elucidate the molecular mechanisms underlying HL. Initially, we built three different but related protein networks, i.e., background network, HL-basic network and HL-specific network. By analyzing these three networks, we investigated the connection characteristic of the HL-related proteins. Subsequently, we explored the miRNA regulation on HL-specific network and analyzed three kinds of simple regulation patterns, i.e., co-regulation of protein pairs, as well as the direct and indirect regulation of triple proteins. Finally, we constructed a simplified protein network combined with the regulation of miRNAs on proteins to better understand the relation between HL-related proteins and miRNAs. CONCLUSIONS: We find that the HL-related proteins are more likely to connect with each other compared to other proteins. Moreover, the HL-specific network can be further divided into five sub-networks and 49 proteins as the backbone of HL-specific network make up and connect these 5 sub-networks. Thus, they may be closely associated with HL. In addition, we find that the co-regulation of protein pairs is the main regulatory pattern of miRNAs on the protein network in the HL-specific network. According to the regulation of miRNA on protein network, we have identified 5 core miRNAs as the potential biomarkers for diagnostic of HL. Finally, several protein pathways have been identified to closely associated with HL, which provides deep insights into underlying mechanism of HL.

Quaternary Solar Cells with 12.5% Efficiency Enabled with Non-Fullerene and Fullerene Acceptor Guests to Improve Open Circuit Voltage and Film Morphology.

Designing the bulk-heterojunction structure (binary, ternary and quaternary) is of great fundamental interest for relaxing the trade-off between open circuit voltage (Voc ) and short circuit current density (   Jsc ). Herein, a new quaternary blended material system is reported with a nonfullerene and PC71 BM as the third and fourth component of PBDB-T:ITCT, leading to simultaneously increased Voc and Jsc and maintained fill factor (FF). The guest IT-T-IC has upshifted LUMO energy level helping to obtain a higher Voc . The further addition of 0.2 PC71 BM as the fourth component yields an even higher Voc because the LUMO of PC71 BM is higher than that of ITCT. Interestingly, the blend of PC71 BM leads to the formation of an unprecedented neuron-like morphology, which acts as new centers not only performing light absorption and charge separation but also charge transport through their surrounding donor and acceptor fibers. The increased hole and electron mobilities and the reduced bimolecular loss results in an even larger Jsc and FF. These results indicate that a combination using a structurally similar higher-LUMO-level non-fullerene acceptor and PCBM is a simple yet effective quaternary material approach to simultaneously increase Voc and Jsc while maintaining FF, improving final device performance.

Source localization by matching sound intensity with a vertical array in the deep ocean.

The characteristics of the reliable acoustic path (RAP) have been widely used to estimate source depth in the deep ocean. Here, a passive broadband source localization method that estimates both depth and range using the interference of the broadband signal with a non-synchronous vertical array in the RAP is demonstrated. The acoustic intensity distribution versus frequency and depth, which includes interference characteristics, is calculated from non-synchronous vertical array data and used to locate the source. Simulations and an experiment conducted in the western Pacific show that this method can successfully locate a broadband submerged source in the range of 10-30 km.

Ventricular septal rupture, right ventricular dissection, and tricuspid chordae rupture--A rare complication after inferior and right ventricular infarction.

A 76-year-old man under stable hemodynamic condition was admitted to our hospital for delayed percutaneous coronary intervention following a diagnosis of acute inferior myocardial infarction. Bedside echocardiography revealed ventricular septal rupture at the basal posteroinferior wall with a large left-to-right shunt. Right ventricular free-wall intramyocardial dissection and tricuspid chordae rupture were noted. Coronary angiography demonstrated occlusion of the proximal right coronary artery, which was treated by balloon angioplasty and stenting. While preparing for surgical repair, the patient's overall cardiac and renal function deteriorated and surgery was contraindicated. The patient died 16 days after discharge.

[Echocardiographic diagnoses of congenital atrial appendage aneurysm: from fetus to adult].

OBJECTIVE: To summarize the echocardiograhic features of atrial appendage aneurysm (AAA) in fetuses, children and adults and evaluate the value of echocardiography in the diagnosis of AAA. METHODS: The AAA echocardiographic features of 6 fetuses, 1 child and 4 adults were retrospectively analyzed. And the diagnoses were confirmed by autopsy, postnatal follow-ups, computed tomography (CT) and surgery. RESULTS: Left atrial appendage aneurysm was more common than right atrial appendage aneurysm. AAA had the same echocardiographic characteristics in fetuses, children and adults. And it was usually combined with other complex cardiac malformations in fetuses while single cardiac abnormality was predominant in children and adults. CONCLUSION: Fetuses, children and adults with AAA may be found by echocardiography in time so that echocardigraphy has an important role in diagnosing AAA.

Corrigendum: Double cross-linked graphene oxide hydrogel for promoting healing of diabetic ulcers.

[This corrects the article DOI: 10.3389/fchem.2024.1355646.].

Double cross-linked graphene oxide hydrogel for promoting healing of diabetic ulcers.

This study explores the synthesis and characterization of a novel double cross-linked hydrogel composed of polyvinyl alcohol (PVA), sodium alginate (SA), graphene oxide (GO), and glutathione (GSH), henceforth referred to as PVA/SA/GO/GSH. This innovative hydrogel system incorporates two distinct types of cross-linking networks and is meticulously engineered to exhibit sensitivity to high glucose and/or reactive oxygen species (ROS) environments. A sequential approach was adopted in the hydrogel formation. The initial phase involved the absorption of GSH onto GO, which was subsequently functionalized with boric acid and polyethylene glycol derivatives via a bio-orthogonal click reaction. This stage constituted the formation of the first chemically cross-linked network. Subsequently, freeze-thaw cycles were utilized to induce a secondary cross-linking process involving PVA and SA, thereby forming the second physically cross-linked network. The resultant PVA/SA/GO/GSH hydrogel retained the advantageous hydrogel properties such as superior water retention capacity and elasticity, and additionally exhibited the ability to responsively release GSH under changes in glucose concentration and/or ROS levels. This feature finds particular relevance in the therapeutic management of diabetic ulcers. Preliminary in vitro evaluation affirmed the hydrogel's biocompatibility and its potential to promote cell migration, inhibit apoptosis, and exhibit antibacterial properties. Further in vivo studies demonstrated that the PVA/SA/GO/GSH hydrogel could facilitate the healing of diabetic ulcer sites by mitigating oxidative stress and regulating glucose levels. Thus, the developed PVA/SA/GO/GSH hydrogel emerges as a promising candidate for diabetic ulcer treatment, owing to its specific bio-responsive traits and therapeutic efficacy.

Sleep disturbance and suicidal ideation mediated by psychotic-like experiences in adolescents: a two-wave longitudinal study.

STUDY OBJECTIVES: Sleep disturbance may cause suicidal ideation (SI). This study aimed to examine their co-occurrence rate among adolescents and investigate whether psychotic-like experiences (PLEs) mediate this association. METHODS: A total of 17 722 Chinese adolescents were included in this two-wave longitudinal study. The baseline survey (time 1, T1) was conducted between April 21 and May 12, 2021, and the follow-up survey (time 2, T2) was implemented between December 17 and 26, 2021. At T1, participants completed questionnaires to assess their sleep disturbance, sleep duration, PLEs, SI, depressive symptoms, and sociodemographic characteristics. At T2, participants reported their PLEs, SI, and negative life events. RESULTS: The SI prevalence decreased from 20.2% (T1) to 18.4% (T2). Participants with SI showed significantly higher prevalence of sleep disturbance and short sleep duration compared to those without SI. Baseline sleep disturbance and short sleep duration were both associated with the increased risk of SI 6 months later. These longitudinal links were mediated by PLEs, independent of baseline covariates and negative life events. CONCLUSIONS: These findings provide a novel insight into the mechanism linking sleep problems and suicidality, and stress the significance of assessing and addressing sleep problems and PLEs for adolescent suicide prevention and intervention.

Single-cell RNA-seq reveals the transcriptional program underlying tumor progression and metastasis in neuroblastoma.

Neuroblastoma (NB) is one of the most common childhood malignancies. Sixty percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor outcomes. However, the molecular mechanisms triggering NB metastasis remain largely uncharacterized. In this study, we generated a transcriptomic atlas of 15 447 NB cells from eight NB samples, including paired samples of primary tumors and bone marrow metastases. We used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common 'starter' subpopulation that initiates tumor development and metastasis. The 'starter' population exhibited high expression levels of multiple cell cycle-related genes, indicating the important role of cell cycle upregulation in NB tumor progression. In addition, our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition (p-EMT) along the metastatic route from the primary site to the bone marrow. Our study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis.

Design of a high-performance NIR-II nanoprobe by steric regulation for in vivo vasculature and tumor imaging.

A novel NIR-II nanoprobe was developed through regulating the steric effect of an A-DA'D-A dye. The probe features the properties of strong fluorescence, high stability, and a large Stokes shift, thereby serving as a remarkable contrast agent for the fluorescence imaging of hindlimb vasculature and tumors in live mice.

Oxygen radical absorbance capacity of different varieties of strawberry and the antioxidant stability in storage.

Total antioxidant capacity of different varieties of strawberry (Ningfeng, Ningyu, Zijin 4, Toyonoka, Benihope, Sweet Charlie) in different developmental stages (including green unripe stages, half red stages, and red ripe stages) was investigated by oxygen radical absorbance capacity (ORAC) assay. In addition, effects of the antioxidant properties of strawberry stored at 4 °C or -18 °C for a period of five months were studied. The results showed that antioxidant capacity of strawberry changed based on tested part, developmental stage, variety, and time of collection. Calyces had significantly higher ORAC values compared with fruits. Strawberry fruits had higher ORAC values during the green unripe stages than the half red stages and red ripe stages. Strawberries got higher ORAC values during short-time storage, and then decreased during long-time storage. Samples stored at -18 °C exhibited higher antioxidant capacity than those stored at 4 °C, while vacuum treatment could further increase ORAC values. The results indicated the potential market role of strawberries as a functional food and could provide great value in preventing oxidation reaction in food processing and storage for the dietary industry.

Changes in sleep disturbance among Chinese adolescents: A population-based online survey.

OBJECTIVE: Sleep disturbance is prevalent among adolescents but little is known about the short-term changes among Chinese adolescents. The study aimed to explore the prevalence and change patterns of sleep disturbance and identify its risk and protective factors. METHODS: Data were collected online from April 21st to May 12th, 2021 (Time 1, T1) and December 17th to 26th, 2021 (Time 2, T2). The final sample comprised 34,260 adolescents. Self-administrated questionnaires were used to assess socio-demographic variables, sleep disturbance, depression, anxiety, life events, family function, and resilience. RESULTS: The prevalence of sleep disturbance was 12.0% at T1 and 11.8% at T2, with higher rates in females than males. Four groups of sleep disturbance change patterns were identified: non-sleep disturbance group (80.4%), persistent group (4.2%), new-onset group (7.6%), and remission group (7.8%). Risk factors for new-onset sleep disturbance included being in junior high school (AOR = 1.26, 95%CI = 1.15-1.38), family history of mental disorders (AOR = 1.49, 95%CI = 1.03-2.15), and moderate (AOR = 1.24, 95%CI = 1.13-1.36) and severe (AOR = 1.48, 95%CI = 1.27-1.72) family dysfunction. Risk factors for persistent sleep disturbance included being in junior (AOR = 1.25, 95%CI = 1.08-1.45) and senior (AOR = 1.53, 95%CI = 1.15-2.03) high school, parental currently unmarried status (AOR = 1.34, 95%CI = 1.05-1.73), moderate (AOR = 1.19, 95%CI = 1.02-1.39) and severe (AOR = 1.28, 95%CI = 1.06-1.55) family dysfunction. Medium (AOR = 0.48, 95%CI = 0.43-0.53) and high (AOR = 0.34, 95%CI = 0.29-0.40) levels of resilience were protective factors against new-onset sleep disturbance, as well as against persistent sleep disturbance (medium level: AOR = 0.51, 95%CI = 0.43-0.60; high level: AOR = 0.32, 95%CI = 0.25-0.43). CONCLUSIONS: Interventions aimed at promoting family functions and enhancing resilience may improve sleep disturbance among adolescents.

Antenna Placement Optimization for Distributed MIMO Radar Based on a Reinforcement Learning Algorithm.

This paper studies an optimization problem of antenna placement for multiple heading angles of the target in a distributed multiple-input multiple-output (MIMO) radar system. An improved method to calculate the system's coverage area in light of the changing target heading is presented. The antenna placement optimization problem is mathematically modelled as a sequential decision problem for compatibility with reinforcement learning solutions. A reinforcement learning agent is established, which uses the long short-term memory (LSTM)-based proximal policy optimization (PPO) method as the core algorithm to solve the antenna placement problem. Finally, the experimental findings demonstrate that the method can enhance the coverage area of antenna placement and thus has reference value for providing new ideas for the antenna placement optimization of distributed MIMO radar.