Liquid-liquid phase separation in diseases.

Liquid-liquid phase separation (LLPS), an emerging biophysical phenomenon, can sequester molecules to implement physiological and pathological functions. LLPS implements the assembly of numerous membraneless chambers, including stress granules and P-bodies, containing RNA and protein. RNA-RNA and RNA-protein interactions play a critical role in LLPS. Scaffolding proteins, through multivalent interactions and external factors, support protein-RNA interaction networks to form condensates involved in a variety of diseases, particularly neurodegenerative diseases and cancer. Modulating LLPS phenomenon in multiple pathogenic proteins for the treatment of neurodegenerative diseases and cancer could present a promising direction, though recent advances in this area are limited. Here, we summarize in detail the complexity of LLPS in constructing signaling pathways and highlight the role of LLPS in neurodegenerative diseases and cancers. We also explore RNA modifications on LLPS to alter diseases progression because these modifications can influence LLPS of certain proteins or the formation of stress granules, and discuss the possibility of proper manipulation of LLPS process to restore cellular homeostasis or develop therapeutic drugs for the eradication of diseases. This review attempts to discuss potential therapeutic opportunities by elaborating on the connection between LLPS, RNA modification, and their roles in diseases.

The evaluation and enhancement strategies of core competencies for older adult caregivers in integrated medical and older adult care institutions.

The study aimed to understand the main skills of older adult caregivers and find ways to improve these skills. We selected participants using a method called random cluster sampling, where caregivers from 17 different medical and nursing care facilities across seven districts in Hangzhou were chosen. We collected 492 valid questionnaires and conducted interviews with 150 people. To analyze the data, we used T-tests and Analysis of Variance (ANOVA) to identify what factors affect caregivers' skills. We also performed multiple regression analysis to explore these factors in more depth. The analysis showed that age (p = 0.041), annual income (p < 0.001), and having a training certificate (p < 0.001) significantly influence the skills of older adult caregivers. Specifically, caregivers' age and whether they had a training certificate were linked to how competent they were, with income being a very strong factor. The study highlighted a gap between the caregivers' current skills and the skills needed for high-quality care. This gap shows the need for training programs that are specifically tailored to the caregivers' diverse needs and cultural backgrounds. Medical and eldercare facilities should adjust their work and educational programs accordingly. It's also important to look at how caregivers are paid to make sure their salary reflects their skills and the quality of care they provide. Finally, it's crucial to integrate a comprehensive training program that leads to certification within eldercare organizations.

Design of an optically transparent and broadband absorber based on a multi-objective optimization algorithm.

In this Letter, an optically transparent and broadband absorber designed using a multi-objective genetic algorithm (MOGA) is proposed. The absorption of the multilayer lossy frequency selective surface-based absorber is calculated by multilayer absorption equations and equivalent circuit models. To solve the problem of the unbalanced structure absorption bandwidth and thickness, an algorithm is used for optimizing the geometric and sheet resistance parameters of the structure. A multilayer and optically transparent absorber with 90% absorption bandwidth covering a frequency range of 2-18 GHz (S-band to Ku-band) is developed based on the MOGA design method with optical transmittance of 60%. Its total thickness consists of a wavelength of only 0.095, and it has high oblique incidence stability, which makes it useful in the stealth technology and transparent electromagnetic shielding applications.

Bioinspired Adaptive Microdrugs Enhance the Chemotherapy of Malignant Glioma: Beyond Their Nanodrugs.

Solid nanoparticle-mediated drug delivery systems are usually confined to nanoscale due to the enhanced permeability and retention effect. However, they remain a great challenge for malignant glioma chemotherapy because of poor drug delivery efficiency and insufficient tumor penetration resulting from the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Inspired by biological microparticles (e.g., cells) with excellent adaptive deformation, it is demonstrated that the adaptive microdrugs (even up to 3.0 µm in size) are more efficient than their nanodrugs (less than 200 nm in size) to cross BBB/BBTB and penetrate into tumor tissues, achieving highly efficient chemotherapy of malignant glioma. The distinct delivery of the adaptive microdrugs is mainly attributed to the enhanced interfacial binding and endocytosis via adaptive deformation. As expected, the obtained adaptive microdrugs exhibit enhanced accumulation, deep penetration, and cellular internalization into tumor tissues in comparison with nanodrugs, significantly improving the survival rate of glioblastoma mice. It is believed that the bioinspired adaptive microdrugs enable them to efficiently cross physiological barriers and deeply penetrate tumor tissues for drug delivery, providing an avenue for the treatment of solid tumors.

The association among thriving in life, quality of life, and suicidal ideation in Chinese urban older adults: the moderating effects of attitude toward own aging.

BACKGROUND: As the global trend of population aging intensifies, the health and well-being of the older population has gradually become a focus of attention for the global community. This study assessed the status of thriving in life among Chinese urban older adults and identified its relationship with attitude toward own aging and quality of life (QoL). It also tested whether attitude toward own aging moderates the association between thriving in life and Qol or between thriving in life and suicidal ideation. METHODS: Primary data were collected through a cross-sectional survey among urban older adults from three provinces in China. They were invited to complete an anonymous survey using face-to-face interviews from December 2019 to January 2020. Data from 764 older adults were analyzed. RESULTS: Approximately 44.39% of participants reported positive responses toward the four domains of thriving in life. Thriving in life and attitude toward own aging had a significant association with QoL. Thriving in life was a protective factor for suicidal ideation for older adults. Moreover, attitude toward own aging moderated the association between thriving in life and QoL and that between thriving in life and suicidal ideation. CONCLUSIONS: Chinese urban older adults were reportedly thriving in life, which contributed to increased QoL and reduced suicidal ideation. Notably, the study revealed that more positive attitudes towards own aging were associated with higher levels of thriving in life, better QoL, and reduced suicidal ideation. Targeted interventions for older adults should be devised to promote thriving in life and prevent negative attitudes of older people towards their own aging, further raising QoL and reducing suicidal ideation.

Identification of candidate genes for Fusarium head blight resistance from QTLs using RIL population in wheat.

Fusarium head blight (FHB) stands out as one of the most devastating wheat diseases and leads to significantly grain yield losses and quality reductions in epidemic years. Exploring quantitative trait loci (QTL) for FHB resistance is a critical step for developing new FHB-resistant varieties. We previously constructed a genetic map of unigenes (UG-Map) according to the physical positions using a set of recombinant-inbred lines (RILs) derived from the cross of 'TN18 × LM6' (TL-RILs). Here, the number of diseased spikelets (NDS) and relative disease index (RDI) for FHB resistance were investigated under four environments using TL-RILs, which were distributed across 13 chromosomes. A number of 36 candidate genes for NDS and RDI from of 19 stable QTLs were identified. The average number of candidate genes per QTL was 1.89, with 14 (73.7%), two (10.5%), and three (15.8%) QTLs including one, two, and 3-10 candidate genes, respectively. Among the 24 candidate genes annotated in the reference genome RefSeq v1.1, the homologous genes of seven candidate genes, including TraesCS4B02G227300 for QNds/Rdi-4BL-4553, TraesCS5B02G303200, TraesCS5B02G303300, TraesCS5B02G303700, TraesCS5B02G303800 and TraesCS5B02G304000 for QNds/Rdi-5BL-9509, and TraesCS7A02G568400 for QNds/Rdi-7AL-14499, were previously reported to be related to FHB resistance in wheat, barely or Brachypodium distachyon. These genes should be closely associated with FHB resistance in wheat. In addition, the homologous genes of five genes, including TraesCS1A02G037600LC for QNds-1AS-2225, TraesCS1D02G017800 and TraesCS1D02G017900 for QNds-1DS-527, TraesCS1D02G018000 for QRdi-1DS-575, and TraesCS4B02G227400 for QNds/Rdi-4BL-4553, were involved in plant defense responses against pathogens. These genes should be likely associated with FHB resistance in wheat.

A Comparative Study of Prevalence and Associated Factors of Social Support Among Chinese Shidu Parents and Non-Shidu Parents.

The number of parents in China who have lost their only child, referred to as shidu parents, currently exceeds one million and is increasing by approximately 76,000 annually. Shidu parents face a unique challenge in long-term care, primarily stemming from the sudden and tragic loss of their only child, which leads to a substantial decrease in their social support network. A multi-stage, stratified, and cluster sampling method was employed across various economic belts. Linear regression analysis was utilized to examine factors associated with the social support status of shidu and non-shidu parents. The level of social support decreases as the severity of depression increases. Shidu parents with grandchildren tend to have good social support. The city of Hangzhou exhibits relatively high levels of social support. Married individuals typically report higher levels of social support. It is recommended to prioritize shidu parents without grandchildren as a primary focus for government and societal support. Key recommendations include strengthening social skills training and developing social support networks. Drive economic development, particularly in relatively underdeveloped regions. Strengthen social organizations and community development. Enhancing access to support services, leveraging technology, and encouraging volunteerism for non-married parents.

Cloning a novel reduced-height (Rht) gene TaOSCA1.4 from a QTL in wheat.

Reducing plant height (PH) is one of the core contents of the "Green Revolution", which began in the 1960s in wheat. A number of 27 reduced-height (Rht) genes have been identified and a great number of quantitative trait loci (QTLs) for PH have been mapped on all 21 chromosomes. Nonetheless, only several genes regulated PH have been cloned. In this study, we found the interval of QTL QPh-1B included an EST-SSR marker swes1079. According to the sequence of swes1079, we cloned the TaOSCA1.4 gene. We developed a CAPS marker to analyze the variation across a natural population. The result showed that the PH was significantly different between the two haplotypes of TaOSCA1.4-1B under most of the 12 environments and the average values of irrigation and rainfed conditions. This result further demonstrated that TaOSCA1.4 was associated with PH. Then, we validated the TaOSCA1.4 via RNAi technology. The average PHs of the wild-type (WT), RNAi lines 1 (Ri-1) and 2 (Ri-2) were 94.6, 83.6 and 79.2 cm, respectively, with significant differences between the WT and Ri-1 and Ri-2. This result indicated that the TaOSCA1.4 gene controls PH. TaOSCA1.4 is a constitutively expressed gene and its protein localizes to the cell membrane. TaOSCA1.4 gene is a member of the OSCA gene family, which regulates intracellular Ca2+ concentration. We hypothesized that knock down mutants of TaOSCA1.4 gene reduced regulatory ability of Ca2+, thus reducing the PH. Furthermore, the cell lengths of the knock down mutants are not significantly different than that of WT. We speculate that TaOSCA1.4 gene is not directly associated with gibberellin (GA), which should be a novel mechanism for a wheat Rht gene.

YTHDC1-Mediated lncRNA MSC-AS1 m6A Modification Potentiates Laryngeal Squamous Cell Carcinoma Development via Repressing ATXN7 Transcription.

Laryngeal squamous cell carcinoma (LSCC) has the highest mortality rate among head and neck squamous cell carcinoma. This study was designed to investigate the biological effect of long noncoding RNA (lncRNA) MSC antisense RNA 1 (MSC-AS1) on LSCC development and the underlying mechanism. The expression and prognostic value of lncRNAs in head and neck squamous cell carcinoma were predicted in the bioinformatics tools. The overexpression of MSC-AS1 in LSCC patients predicted a poor prognosis. Depletion of MSC-AS1 using shRNA repressed the malignant phenotype of AMC-HN-8 and TU-177 cells. MSC-AS1, mainly localized in the nucleus, interacted closely with the transcription factor CCCTC-binding factor (CTCF). CTCF played anti-tumor effects in vitro and in vivo. Ataxin-7 (ATXN7) was predicted to be a downstream target of CTCF, whose expression was negatively controlled by MSC-AS1. MSC-AS1 was found to block the expression of CTCF, thereby repressing ATXN7. Finally, MSC-AS1 overexpression in LSCC was governed by YTH domain-containing protein 1 (YTHDC1)-mediated m6A modification. In summary, our research identified the YTHDC1/MSC-AS1/CTCF/ATXN7 axis in LSCC development, which indicated that MSC-AS1 is an attractive biomarker in the LSCC treatment.

Developing defined starter culture for reproducible profile of flavour compound in Chinese xiaoqu baijiu fermentation.

Defined starter cultures, containing selected microbes could reduce the complexity of natural starter, are beneficial for controllable food fermentations. However, there are challenges in identifying key microbiota and constructing synthetic microbiota for traditional food fermentations. Here, we aimed to develop a defined starter culture for reproducible profile of flavour compounds, using Chinese Xiaoqu Baijiu fermentation as a case. We classified all microbes into 4 modules using weighted correlation network analysis. Module 3 presented significant correlations with flavour compounds (P < 0.05) and the highest gene abundance related with flavour compound production. 13 dominant species in module 3 were selected for mixed culture fermentation, and each species was individually deleted to analyse the effect on flavour compound production. Ten species, presenting significant effects (P < 0.05) on flavour compound production, were selected for developing the starter culture, including Rhizopus oryzae, Rhizopus microsporus, Saccharomyces cerevisiae, Pichia kudriavzevii, Wickerhamomyces anomalus, Lactobacillus acetotolerans, Levilactobacillus brevis, Weissella paramesenteroides, Pediococcus acidilactici, and Leuconostoc pseudomesenteroides. After optimising the structure of the starter culture, the profile similarity of flavour compounds produced by the starter culture reached 81.88% with that by the natural starter. This work indicated feasibility of reproducible profile of flavour compounds with defined starter culture for food fermentations.

Theoretical insights into selective extraction of Am(III) from Cm(III) and Eu(III) with asymmetric N-heterocyclic ligands.

Separation of lanthanide (Ln) and minor actinide (MA) elements and mutual separation between minor actinide elements (e.g. Am(III) and Cm(III)) represent a crucial undertaking. However, separating these elements poses a significant challenge owing to their highly similar physicochemical properties. Asymmetric N-heterocyclic ligands such as N-ethyl-6-(1H-pyrazol-3-yl)-N-(p-tolyl)picolinamide (Et-p-Tol-A-PzPy) and N-ethyl-N-(p-tolyl)-1,10-phenanthroline-2-carboxamide (ETPhenAm) have recently received considerable attention in the separation of MAs over Ln from acid solutions. By changing the central skeleton structures of these ligands and introducing substituents with different properties on the side chains, their complexation behavior with Am(III), Cm(III), and Eu(III) may be affected. In this work, we explore four different asymmetric N-containing heterocyclic ligands, namely Et-p-Tol-A-PzPy (L1), N-ethyl-6'-(1H-pyrazol-3-yl)-N-(p-tolyl)-[2,2'-bipyridine]-6-carboxamide (L2), N-ethyl-9-(1H-pyrazol-3-yl)-N-(p-tolyl)-1,10-phenanthroline-2-carboxamide (L3), and ETPhenAm (L4) using density functional theory (DFT). The calculated results demonstrate the potential of ligands L1-L4 for the extraction and separation of Am(III), Cm(III), and Eu(III). Ligand analysis shows that ligand L3 binds more easily to the central metal atom, in line with the stronger extraction capacity of L3. In spite of the higher covalence between the side chain and the central metal atom for complexes with L1-L3, the main chain seems to control the stability of the extraction complexes. The preorganized 1,10-phenanthroline backbone also further enhances the extraction performance of L3 and L4. The difference in coordination ability between the side chain donors of these ligands and metal ions may affect their separation efficiency. This work presents theoretical insights into synthesizing novel ligands for separating trivalent actinides by adjusting N-heterocyclic ligands.

Tuning the Dynamic Reaction Balance of CRISPR/Cas12a and RPA in One Pot: A Key to Switch Nucleic Acid Quantification.

Excavating nucleic acid quantitative capabilities by combining clustered regularly interspaced short palindromic repeats (CRISPR) and isothermal amplification in one pot is of common interest. However, the mutual interference between CRISPR cleavage and isothermal amplification is the primary obstacle to quantitative detection. Though several works have demonstrated enhanced detection sensitivity by reducing the inhibition of CRISPR on amplification in one pot, few paid attention to the amplification process and even dynamic reaction processes between the two. Herein, we find that DNA quantification can be realized by regulating either recombinase polymerase amplification (RPA) efficiency or CRISPR/Cas12a cleaving efficiency (namely, tuning the dynamic reaction balance) in one pot. The sensitive quantification is realized by utilizing dual PAM-free crRNAs for CRISPR/Cas12a recognition. The varied RPA primer concentration with stabilized CRISPR systems significantly affects the amplification efficiency and quantitative performances. Alternatively, quantitative detection can also be achieved by stabilizing the amplification process while regulating the CRISPR/Cas12a concentration. The quantitative capability is proved by detecting DNA targets from Lactobacillus acetotolerans and SARS-CoV-2. The quantitative performance toward real samples is comparable to quantitative real-time PCR for detecting L. acetotolerans spiked in fermented food samples and SARS-CoV-2 clinical samples. We expect that the presented method will be a powerful tool for quantifying other nucleic acid targets.

The Changes in Fecal Bacterial Communities in Goats Offered Rumen-Protected Fat.

Leizhou goats are famous for their delicious meat but have inferior growth performance. There is little information on rumen-protected fat (RPF) from the Leizhou goat. Hence, we observed the effects of RPF on growth, fecal short-chain fatty acids, and bacteria community with respect to Leizhou goats. Twelve goats (13.34 ± 0.024 kg) were selected and assigned randomly to one of two treatments: (1) a control diet (CON) and (2) 2.4% RPF with a control diet (RPF). The final body weight and average daily gain (ADG) were greater (p < 0.05), and the dry matter intake (DMI): ADG was lower (p < 0.05) in the RPF group than in the CON group. There were no differences in DMI between the CON and RPF groups. The concentrations of total short-chain fatty acids, acetate, propionate, and butyrate were lower (p < 0.05) in the RPF group than in the CON group. The relative abundances of Ruminococcus, Rikenellaceae_RC9_gut_group, Treponema, norank_f__norank_o__RF39, Eubacterium_siraeum_group, and Ruminococcus_torques_group were lower (p < 0.05) in the RPF group than in the CON group. The relative abundances of Bacteroides, norank_f__norank_o__Clostridia_UCG-014, norank_f__Eubacterium_coprostanoligenes_group, Eubacterium_ruminantium_group, norank_f__Oscillospirale-UCG-010, Oscillospiraceae_UCG-002, and Family_XIII_AD3011_group were greater (p < 0.05) in the RPF group than in the CON group. It was concluded that RPF could improve the goats' growth performance by regulating their fecal bacteria communities.

Complex-Amplitude Programmable Versatile Metasurface Platform Driven by Guided Wave.

Metasurfaces have shown unparalleled controllability of electromagnetic (EM) waves. However, most of the metasurfaces need external spatial feeding sources, which renders practical implementation quite challenging. Here, a low-profile programmable metasurface with 0.05λ0 thickness driven by guided waves is proposed to achieve dynamic control of both amplitude and phase simultaneously. The metasurface is fed by a guided wave traveling in a substrate-integrated waveguide, avoiding external spatial sources and complex power divider networks. By manipulating the state of the p-i-n diodes embedded in each meta-atom, the proposed metasurface enables 1-bit amplitude switching between radiating and nonradiating states, as well as a 1-bit phase switching between 0° and 180°. As a proof of concept, two advanced functionalities, namely, low sidelobe-level beam scanning and Airy beam generation, are experimentally demonstrated with a single platform operating in the far- and near-field respectively. Such complex-amplitude, programmable, and low-profile metasurfaces can overcome integration limitations of traditional metasurfaces, and open up new avenues for more accurate and advanced EM wave control within an unprecedented degree of freedom.

Mediating effect of depressive symptoms on the relationship of chronic pain and cardiovascular diseases among Chinese population: Evidence from the CHARLS.

OBJECTIVE: Few studies have examined the direct or indirect effect of chronic pain on cardiovascular diseases (CVD) within Chinese population. The objective aimed to investigate the mediating role of depressive symptoms between chronic pain and CVD. METHODS: 6522 participants from China Health and Retirement Longitudinal Study were included in this retrospective cohort study. The main endpoint was the occurrence of CVD. Weighted multivariate logistic regression was used to assess the association between chronic pain and depressive symptoms. Distribution-of-product method was employed to examine the mediation effect of depressive symptoms. Subgroup analyses were performed. RESULTS: 219 developed CVD at the end of follow-up period. After adjusting all confounding variables, chronic pain was associated with increased risk of depressive symptoms in total population [odds ratio (OR) = 3.85, 95%confidence interval (CI): 3.35-4.42]. Among total population, there was a positive association of chronic pain and CVD [risk ratio (RR)a = 2.00, 95% CI: 1.33-3.00] (total effect). After further adjusting depressive symptoms, the association between chronic pain and CVD was significant (RRb = 1.67, 95% CI: 1.16-2.41) (direct effect). According to the distribution-of-product test, we observed a mediating effect of depressive symptoms on the relationship between chronic pain and CVD with the percentage of mediation of 32.8%. The mediating effect of depression was observed in individuals of aged45-65 years old, female participants, participants who never drinking and not have hypertension. CONCLUSION: Chronic pain was positively associated with CVD for Chinese population, and depressive symptoms was considered to mediate the association between chronic pain and CVD.

YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS.

N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, has not been previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells and asthmatic patients and that it influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid-liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules. Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and interleukin-1ß secretion leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation.

Optimization of Chinese land spatial pattern in the transformation process of resource-based cities: a case study in Tongling City, China.

Optimizing the spatial layout of the national territory is crucial for realizing the transformation and development of resource-oriented cities in the context of high-quality development in the new period. This paper takes Tongling City as a case study, based on the analysis of the historical development foundation, then uses the SD-FLUS comprehensive model to carry out a systematic analysis of the transformation in five dimensions of economy, society, population, science and technology, resources and environment, and discusses the optimization of spatial pattern under the contextual simulation. The conclusions are as follows: ① The hierarchical framework of "system-indicator-element" is not only internally interconnected, but also inextricably linked with the relationship between the various categories of the land use system. ② Decrease of cropland, forest, water, grassland, and barren decreases from the economic development, social progress, and comprehensive development, and there is a small increase in the area under the scenario of resource and environmental protection, and the direction of the change of the impervious is in the opposite direction. ③ Cultivated land is retained in situ and concentrated to a small extent, forested land is reduced to a small extent while the status quo is maintained, and the Yangtze River water system will be retained and protected to a large extent, but part of the waters of Zongyang County will give way to the expansion of construction land under the development objectives of the new county. Building land will be expanded and extended to the northeast in the original site area, while the southwest corner of the original county center will be expanded to some extent in Zongyang County to promote the county's economic development.

Oridonin inhibited epithelial-mesenchymal transition of laryngeal carcinoma by positively regulating LKB1/AMPK signaling.

Oridonin is the main bioactive component of Rabdosia rubescens, and its anticancer activity has been reported in a variety of cancers. However, the molecular mechanism of oridonin in laryngeal carcinoma remains unclear. In the present study, the cytotoxic effect of oridonin on laryngeal carcinoma Hep-2 and TU212 cell lines were initially detected by modified MTT assay. The results showed that oridonin had a dose-dependent anti-proliferative effect on laryngeal carcinoma Hep-2 and TU212 cells. Next, we found that oridonin significantly inhibited the migration and invasion of human laryngeal carcinoma Hep-2 and TU212 cell lines by wound healing assay and transwell assay. Subsequently, the results of quantitative real-time PCR assay and western blotting assay confirmed that oridonin upregulated the expression of E-cadherin while downregulated the expression of N-cadherin in a concentration-dependent manner at mRNA and protein levels. In addition, phosphorylation levels of liver kinase B1 (p-LKB1) and AMP-activated protein kinase (p-AMPK) were also elevated upon oridonin treatment. To further verify the role of LKB1/AMPK signaling pathway in laryngeal carcinoma, overexpression of LKB1 was constructed by plasmid transfection. The data exhibited that overexpression of LKB1 could further reinforce the increase of E-cadherin level and decrease of N-cadherin level mediated by oridonin. Additionally, AMPK inhibitor compound C could reverse anti-metastatic effect of oridonin on laryngeal carcinoma, and antagonise EMT expression. In contrast, AMPK activator AICAR presented the opposite effect. In conclusion, our study revealed that oridonin could remarkably reverse the epithelial-mesenchymal transition of laryngeal carcinoma by positively regulating LKB1/AMPK signaling pathway, which suggested that oridonin may be a potential candidate for the treatment of laryngeal carcinoma in the future.

4f/5d Hybridization Induced Single-Electron Delocalization in an Azide-Bridged Dicerium Complex.

Dilanthanide complexes with one-electron delocalization are important targets for understanding the specific 4f/5d-bonding feature in lanthanide chemistry. Here, we report an isolable azide-bridged dicerium complex 3 [{(TrapenTMS)Ce}2(µ-N3)]• [Trapen = tris (2-aminobenzyl)amine; TMS = SiMe3], which is synthesized by the reaction of tripodal ligand-supported (TrapenTMS)CeIVCl complex 2 with NaN3. The structure and bonding nature of 3 are fully characterized by X-ray crystal diffraction analysis, electron paramagnetic resonance (EPR), magnetic measurement, cyclic voltammetry, X-ray absorption spectroscopy, and quantum-theoretical studies. Complex 3 presents a trans-bent central Ce-N3-Ce unit with a single electron of two mixed-valent Ce atoms. The unique low-temperature (2 K) anisotropic EPR signals [g = 1.135, 2.003, and 3.034] of 3 indicate that its spin density is distributed on the central Ce-N3-Ce unit with marked electron delocalization. Quantum chemical analyses show strong 4f/5d orbital mixing in the singly occupied molecular orbital of 3, which allows for the unpaired electron to extend throughout the cerium-azide-cerium unit via a multicentered one-electron (Ce-N3-Ce) interaction. This work extends the family of mixed-valent dilanthanide complexes and provides a paradigm for understanding the bonding motif of ligand-bridged dilanthanide complexes.

Development and Validation of a Deep-Learning Network for Detecting Congenital Heart Disease from Multi-View Multi-Modal Transthoracic Echocardiograms.

Early detection and treatment of congenital heart disease (CHD) can significantly improve the prognosis of children. However, inexperienced sonographers often face difficulties in recognizing CHD through transthoracic echocardiogram (TTE) images. In this study, 2-dimensional (2D) and Doppler TTEs of children collected from 2 clinical groups from Beijing Children's Hospital between 2018 and 2022 were analyzed, including views of apical 4 chamber, subxiphoid long-axis view of 2 atria, parasternal long-axis view of the left ventricle, parasternal short-axis view of aorta, and suprasternal long-axis view. A deep learning (DL) framework was developed to identify cardiac views, integrate information from various views and modalities, visualize the high-risk region, and predict the probability of the subject being normal or having an atrial septal defect (ASD) or a ventricular septaldefect (VSD). A total of 1,932 children (1,255 healthy controls, 292 ASDs, and 385 VSDs) were collected from 2 clinical groups. For view classification, the DL model reached a mean [SD] accuracy of 0.989 [0.001]. For CHD screening, the model using both 2D and Doppler TTEs with 5 views achieved a mean [SD] area under the receiver operating characteristic curve (AUC) of 0.996 [0.000] and an accuracy of 0.994 [0.002] for within-center evaluation while reaching a mean [SD] AUC of 0.990 [0.003] and an accuracy of 0.993 [0.001] for cross-center test set. For the classification of healthy, ASD, and VSD, the model reached the mean [SD] accuracy of 0.991 [0.002] and 0.986 [0.001] for within- and cross-center evaluation, respectively. The DL models aggregating TTEs with more modalities and scanning views attained superior performance to approximate that of experienced sonographers. The incorporation of multiple views and modalities of TTEs in the model enables accurate identification of children with CHD in a noninvasive manner, suggesting the potential to enhance CHD detection performance and simplify the screening process.