A single photoreceptor splits perception and entrainment by cotransmission.

Vision enables both image-forming perception, driven by a contrast-based pathway, and unconscious non-image-forming circadian photoentrainment, driven by an irradiance-based pathway1,2. Although two distinct photoreceptor populations are specialized for each visual task3-6, image-forming photoreceptors can additionally contribute to photoentrainment of the circadian clock in different species7-15. However, it is unknown how the image-forming photoreceptor pathway can functionally implement the segregation of irradiance signals required for circadian photoentrainment from contrast signals required for image perception. Here we report that the Drosophila R8 photoreceptor separates image-forming and irradiance signals by co-transmitting two neurotransmitters, histamine and acetylcholine. This segregation is further established postsynaptically by histamine-receptor-expressing unicolumnar retinotopic neurons and acetylcholine-receptor-expressing multicolumnar integration neurons. The acetylcholine transmission from R8 photoreceptors is sustained by an autocrine negative feedback of the cotransmitted histamine during the light phase of light-dark cycles. At the behavioural level, elimination of histamine and acetylcholine transmission impairs R8-driven motion detection and circadian photoentrainment, respectively. Thus, a single type of photoreceptor can achieve the dichotomy of visual perception and circadian photoentrainment as early as the first visual synapses, revealing a simple yet robust mechanism to segregate and translate distinct sensory features into different animal behaviours.

Biospecific Chemistry for Covalent Linking of Biomacromolecules.

Interactions among biomacromolecules, predominantly noncovalent, underpin biological processes. However, recent advancements in biospecific chemistry have enabled the creation of specific covalent bonds between biomolecules, both in vitro and in vivo. This Review traces the evolution of biospecific chemistry in proteins, emphasizing the role of genetically encoded latent bioreactive amino acids. These amino acids react selectively with adjacent natural groups through proximity-enabled bioreactivity, enabling targeted covalent linkages. We explore various latent bioreactive amino acids designed to target different protein residues, ribonucleic acids, and carbohydrates. We then discuss how these novel covalent linkages can drive challenging protein properties and capture transient protein-protein and protein-RNA interactions in vivo. Additionally, we examine the application of covalent peptides as potential therapeutic agents and site-specific conjugates for native antibodies, highlighting their capacity to form stable linkages with target molecules. A significant focus is placed on proximity-enabled reactive therapeutics (PERx), a pioneering technology in covalent protein therapeutics. We detail its wide-ranging applications in immunotherapy, viral neutralization, and targeted radionuclide therapy. Finally, we present a perspective on the existing challenges within biospecific chemistry and discuss the potential avenues for future exploration and advancement in this rapidly evolving field.

Rapid and Repeated Climate Adaptation Involving Chromosome Inversions following Invasion of an Insect.

Following invasion, insects can become adapted to conditions experienced in their invasive range, but there are few studies on the speed of adaptation and its genomic basis. Here, we examine a small insect pest, Thrips palmi, following its contemporary range expansion across a sharp climate gradient from the subtropics to temperate areas. We first found a geographically associated population genetic structure and inferred a stepping-stone dispersal pattern in this pest from the open fields of southern China to greenhouse environments of northern regions, with limited gene flow after colonization. In common garden experiments, both the field and greenhouse groups exhibited clinal patterns in thermal tolerance as measured by critical thermal maximum (CTmax) closely linked with latitude and temperature variables. A selection experiment reinforced the evolutionary potential of CTmax with an estimated h2 of 6.8% for the trait. We identified 3 inversions in the genome that were closely associated with CTmax, accounting for 49.9%, 19.6%, and 8.6% of the variance in CTmax among populations. Other genomic variations in CTmax outside the inversion region were specific to certain populations but functionally conserved. These findings highlight rapid adaptation to CTmax in both open field and greenhouse populations and reiterate the importance of inversions behaving as large-effect alleles in climate adaptation.

Endocytosis triggers V-ATPase-SYK-mediated priming of cGAS activation and innate immune response.

The current view of nucleic acid-mediated innate immunity is that binding of intracellular sensors to nucleic acids is sufficient for their activation. Here, we report that endocytosis of virus or foreign DNA initiates a priming signal for the DNA sensor cyclic GMP-AMP synthase (cGAS)-mediated innate immune response. Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H+ pump (V-ATPase), where SYK is activated and then phosphorylates human cGASY214/215 (mouse cGasY200/201) to prime its activation. Upon binding to DNA, the primed cGAS initiates robust cGAMP production and mediator of IRF3 activation/stimulator of interferon genes-dependent innate immune response. Consistently, blocking the V-ATPase-SYK axis impairs DNA virus- and transfected DNA-induced cGAMP production and expression of antiviral genes. Our findings reveal that V-ATPase-SYK-mediated tyrosine phosphorylation of cGAS following endocytosis of virus or other cargos serves as a priming signal for cGAS activation and innate immune response.

Salivary Proteome and Intact N-Glycopeptides Analysis Reveal Specific Signatures in Periodontitis.

Periodontitis is a prevalent oral inflammatory disease that can result in tooth loss and is closely linked to type 2 diabetes (T2D). In this study, we analyzed the salivary proteome and intact N-glycopeptides (IGPs) of individuals with mild-moderate, severe, aggressive periodontitis, and periodontitis with T2D, including those treated with antidiabetic drugs, to identify specific signatures associated with the disease. Our results revealed that salivary proteins and glycoproteins were altered in all periodontitis groups (PRIDE ID: 1-20230612-72345), with fucose- and sialic acid-containing N-glycans showing the greatest increase. Additionally, differentially expressed proteins were classified into 9 clusters, including those that were increased in all periodontitis groups and those that were only altered in certain types of periodontitis. Interestingly, treatment with antidiabetic drugs reversed many of the changes observed in the salivary proteome and IGPs in T2D-related periodontitis, suggesting a potential therapeutic approach for managing periodontitis in patients with T2D. Consistent with MS/MS results, the expression of salivary IGHA2 and Fucα1-3/6GlcNAc (AAL) was significantly increased in MP. These findings provide new insights into the pathogenesis of periodontitis and highlight the potential of salivary biomarkers for diagnosis, prognosis, and monitoring of disease progression and treatment response.

Tadpole-Like Polar Molecule Encapsulated in a Two-in-One Supramolecular Cage: Molecular Motion, Phase Transition and Ferroelectricity.

Molecule-inclusive closed cage compounds present a unique platform for molecular motion in an isolated environment. This study showcases the incorporation of a tadpole-like polar molecule (1-propyl-1H-imidazole, PIm) into a supramolecular cage formed by duad semicage p-tert-butylcalix[4]arene. The ferroelectric phase transition as well as the cage-confined motion of encapsulated PIm was studied in detail. The unusual quadrastable state of the PIm in the paraelectric phase allows for the modulation of dipolar polarization over a broad temperature/frequency range. This compound represents the first example of a clathrate molecular ferroelectric featuring a molecule-inclusive supramolecular cage, and it also contributes to the understanding of cage-confined molecular dynamics.

Phase Engineering of Zirconium MOFs Enables Efficient Osmotic Energy Conversion: Structural Evolution Unveiled by Direct Imaging.

Creating structural defects in a controlled manner within metal-organic frameworks (MOFs) poses a significant challenge for synthesis, and concurrently, identifying the types and distributions of these defects is also a formidable task for characterization. In this study, we demonstrate that by employing 2-sulfonylterephthalic acid as the ligand for synthesizing Zr (or Hf)-based MOFs, a crystal phase transformation from the common fcu topology to the rare jmt topology can be easily facilitated using a straightforward mixed-solvent strategy. The jmt phase, characterized by an extensively open framework, can be considered a derivative of the fcu phase, generated through the introduction of missing-cluster defects. We have explicitly identified both MOF phases, their intermediate states, and the novel core-shell structures they form using ultralow-dose high-resolution transmission electron microscopy. In addition to facilitating phase engineering, the incorporation of sulfonic groups in MOFs imparts ionic selectivity, making them applicable for osmotic energy harvesting through mixed matrix membrane fabrication. The membrane containing the jmt-phase MOF exhibits an exceptionally high peak power density of 10.08 W m-2 under a 50-fold salinity gradient (NaCl: 0.5 M|0.01 M), which surpasses the threshold of 5 W m-2 for commercial applications and can be attributed to the combination of large pore size, extensive porosity, and abundant sulfonic groups in this novel MOF material.

DNA Nanospheres Assisted Spatial Confinement Signal Amplification for MicroRNA Imaging in Live Cancer Cells.

DNA assemblies are commonly used in biosensing, particularly for the detection and imaging of microRNAs (miRNAs), which are biomarkers associated with tumor progression. However, the difficulty lies in the exploration of high-sensitivity analytical techniques for miRNA due to its limited presence in living cells. In this study, we introduced a DNA nanosphere (DS) enhanced catalytic hairpin assembly (CHA) system for the detection and imaging of intracellular miR-21. The single-stranded DNA with four palindromic portions and extending sequences at the terminal was annealed for assembling DS, which avoided the complex sequence design and high cost of long DNA strands. Benefiting from the multiple modification sites of DS, functional hairpins H1 (modified with Cy3 and BHQ2) and H2 were grafted onto the surface of DS for assembling DS-H1-H2 using a hybridization reaction. The DS-H1-H2 system utilized spatial confinement and the CHA reaction to amplify fluorescence signals of Cy3. This enabled highly sensitive and rapid detection of miR-21 in the range from 0.05 to 3.5 nM. The system achieved a limit of determination (LOD) of 2.0 pM, which was 56 times lower than that of the control CHA circuit with freedom hairpins. Additionally, the sensitivity was improved by 8 times. Moreover, DS-H1-H2 also showed an excellent imaging capability for endogenous miR-21 in tumor cells. This was due to enhanced cell internalization efficiency, accelerated reaction kinetics, and improved biostability. The imaging strategy was shown to effectively monitor the dynamic content of miR-21 in live cancer cells and differentiate various cells. In general, the simple nanostructure DS not only enhanced the detection and imaging capability of the conventional probe but also could be easily integrated with the reported DNA-free probe, indicating a wide range of potential applications.

Heterogeneous Analysis of Extracellular Vesicles for Osteosarcoma Diagnosis.

Osteosarcoma (OS) is the most prevalent primary tumor of bones, often diagnosed late with a poor prognosis. Currently, few effective biomarkers or diagnostic methods have been developed for early OS detection with high confidence, especially for metastatic OS. Tumor-derived extracellular vesicles (EVs) are emerging as promising biomarkers for early cancer diagnosis through liquid biopsy. Here, we report a plasmonic imaging-based biosensing technique, termed subpopulation protein analysis by single EV counting (SPASEC), for size-dependent EV subpopulation analysis. In our SPASEC platform, EVs are accurately sized and counted on plasmonic sensor chips coated with OS-specific antibodies. Subsequently, EVs are categorized into distinct subpopulations based on their sizes, and the membrane proteins of each size-dependent subpopulation are profiled. We measured the heterogeneous expression levels of the EV markers (CD63, BMP2, GD2, and N-cadherin) in each of the EV subsets from both OS cell lines and clinical plasma samples. Using the linear discriminant analysis (LDA) model, the combination of four markers is applied to classify the healthy donors (n = 37), nonmetastatic OS patients (n = 13), and metastatic patients (n = 12) with an area under the curve of 0.95, 0.92, and 0.99, respectively. SPASEC provides accurate EV sensing technology for early OS diagnosis.

Stress Mitigation of Nanosilicon Anode to Achieve Energy-Dense and Highly-Stable Full Cell.

Nanosilicon (nano-Si) anode is subjected to significant stress concentration, which is caused by extrusion deformation of expanded Si nanoparticles with uneven distribution. The low-strength binder and adhesive interface are unable to withstand the stress, resulting in exfoliation and impeding the use of nano-Si anodes. This work aims to mitigate stress in a Si anode with flexible copper (Cu) skeletons that are metallurgically bonded to uniformly distributed Si nanoparticles. It is worth noting that the proposed porous Si-Cu anode exhibits improved high-load cycling performance and promising potential in the full cell, with an energy density of 463 Wh kg-1 at 0.5 C and retention of 81% after 500 cycles at 2 C. Chemo-mechanical simulation and in (ex) situ observation demonstrate that expansion stress is reduced and more evenly distributed in the anode due to uniform distribution of Si nanoparticles, flexible Cu skeletons, and adequate pores. More importantly, the stress is primarily distributed in the flexible Cu skeletons and bonding interface, preventing anode exfoliation, and ensuring efficient lithium ion/electron transference. This work sheds light on the structure construction of an alloy-type anode.

The double flower variant of yellowhorn is due to a LINE1 transposon-mediated insertion.

As essential organs of reproduction in angiosperms, flowers, and the genetic mechanisms of their development have been well characterized in many plant species but not in the woody tree yellowhorn (Xanthoceras sorbifolium). Here, we focused on the double flower phenotype in yellowhorn, which has high ornamental value. We found a candidate C-class gene, AGAMOUS1 (XsAG1), through bovine serum albumin sequencing and genetics analysis with a Long Interpersed Nuclear Elements 1 (LINE1) transposable element fragment (Xsag1-LINE1-1) inserted into its second intron that caused a loss-of-C-function and therefore the double flower phenotype. In situ hybridization of XsAG1 and analysis of the expression levels of other ABC genes were used to identify differences between single- and double-flower development processes. These findings enrich our understanding of double flower formation in yellowhorn and provide evidence that transposon insertions into genes can reshape plant traits in forest trees.

Clinical and genetic characteristics in a Chinese cohort of complex spastic paraplegia type 4.

Spastic paraplegia type 4 (SPG4), caused by SPAST mutations, is the most predominant subtype of hereditary spastic paraplegia. Most documented SPG4 patients present as pure form, with the complex form rarely reported. We described the clinical and genetic features of 20 patients with complex phenotypes of SPG4 and further explored the genotype-phenotype correlations. We collected detailed clinical data of all SPG4 patients and assessed their phenotypes. SPAST gene mutations were identified by Multiplex ligation-dependent probe amplification in combination with whole exome sequencing. We further performed statistical analysis in genotype and phenotype among patients with various manifestations and different variants. Out of 90 SPG4 patients, 20 patients (male:female = 16:4) with additional neurologic deficits, namely complex form, were included in our study. The bimodal distribution of age of onset at 0-10 and 21-40 years old is concluded. On cranial MRI, obvious white matter lesions can be observed in five patients. We identified 9 novel and 8 reported SPAST mutations, of which 11 mutations were located in AAA (ATPase associated with various cellular activities) domain. The AAA cassette of spastin is the hottest mutated region among complex SPG4. All patients with cognitive impairment (CI) are males (n = 9/9). Additionally, 80% patients with ataxia are due to frameshift mutations (n = 4/5). Overall, our study summarized and analyzed the genetic and phenotypic characteristics of complex SPG4, making up over 1/5 of in-house SPG4 cohort, among which CI and ataxia are the most common features. Further studies are expected to explore the underlying mechanisms.

Laparoscopic liver resection versus radiofrequency ablation for small hepatocellular carcinoma: randomized clinical trial.

BACKGROUND: The aim of this study was to compare the efficacy of laparoscopic liver resection versus radiofrequency ablation for treatment of small hepatocellular carcinoma. METHODS: This single-centre RCT was conducted at a tertiary referral centre in China. Patients with small hepatocellular carcinoma who had a single nodule no larger than 5 cm, or up to three nodules of 3 cm or smaller, were eligible. Patients were assigned randomly in a 1 : 1 ratio to either laparoscopic liver resection or radiofrequency ablation. Blinding was not attempted. Sample size calculations led to 75 patients per group. The primary outcome was overall survival, and the secondary outcome was recurrence-free survival. RESULTS: Seventy-five patients were included in each group. Overall survival (HR 1.26, 95% c.i. 0.69 to 2.30; P = 0.451) and recurrence-free survival (HR 1.34, 0.86 to 2.08; P = 0.189) did not differ between the resection and ablation groups. The 1-, 3- and 5-year overall survival rates were 94.7, 80.0, and 74.7% respectively after laparoscopic liver resection versus 93.3, 78.7, and 67.9% after radiofrequency ablation. Corresponding recurrence-free survival rates were 78.7, 61.3, and 51.6%, and 69.3, 53.3, and 41.0%, respectively. CONCLUSION: For small hepatocellular carcinoma, percutaneous radiofrequency ablation provides therapeutic effects similar to those of laparoscopic liver resection. REGISTRATION NUMBER: NCT02243384 (http://www.clinicaltrials.gov).

Percutaneous radiofrequency ablation may provide similar therapeutic effects to laparoscopic liver resection for patients with small hepatocellular carcinoma. This study compared the two treatments. Survival was similar after the two treatments. The choice of treatment may depend on the patient's preference and local availability.

Charge-Assisted Ionic Hydrogen-Bonded Organic Frameworks: Designable and Stabilized Multifunctional Materials.

Hydrogen-bonded organic frameworks (HOFs) are a class of crystalline framework materials assembled by hydrogen bonds. HOFs have the advantages of high crystallinity, mild reaction conditions, good solution processability, and reproducibility. Coupled with the reversibility and flexibility of hydrogen bonds, HOFs can be assembled into a wide diversity of crystalline structures. Since the bonding energy of hydrogen bonds is lower than that of ligand and covalent bonds, the framework of HOFs is prone to collapse after desolventisation and the stability is not high, which limits the development and application of HOFs. In recent years, numerous stable and functional HOFs have been developed by π-π stacking, highly interpenetrated networks, charge-assisted, ligand-bond-assisted, molecular weaving, and covalent cross-linking. Charge-assisted ionic HOFs introduce electrostatic attraction into HOFs to improve stability while enriching structural diversity and functionality. In this paper, we review the development, the principles of rational design and assembly of charge-assisted ionic HOFs, and introduces the different building block construction modes of charge-assisted ionic HOFs. Highlight the applications of charge-assisted ionic HOFs in gas adsorption and separation, proton conduction, biological applications, etc., and prospects for the diverse design of charge-assisted ionic HOFs structures and multifunctional applications.

Clinical and Genetic Spectrum in a Large Cohort of Hereditary Spastic Paraplegia.

BACKGROUND: Next-generation sequencing-based molecular assessment has benefited the diagnosis of hereditary spastic paraplegia (HSP) subtypes. However, the clinical and genetic spectrum of HSP due to large fragment deletions/duplications has yet to be fully defined. OBJECTIVE: We aim to better characterize the clinical phenotypes and genetic features of HSP and to provide new thoughts on diagnosis. METHODS: Whole-exome sequencing (WES) was performed in patients with clinically suspected HSP, followed by multiple ligation-dependent probe amplification (MLPA) sequentially carried out for those with negative findings in known causative genes. Genotype-phenotype correlation analyses were conducted under specific genotypes. RESULTS: We made a genetic diagnosis in 60% (162/270) of patients, of whom 48.9% (132/270) had 24 various subtypes due to point mutations (SPG4/SPG11/SPG35/SPG7/SPG10/SPG5/SPG3A/SPG2/SPG76/SPG30/SPG6/SPG9A/SPG12/SPG15/SPG17/SPG18/SPG26/SPG49/SPG55/SPG56/SPG57/SPG62/SPG78/SPG80). Thirty patients were found to have causative rearrangements by MLPA (11.1%), among which SPG4 was the most prevalent (73.3%), followed by SPG3A (16.7%), SPG6 (3.3%), SPG7 (3.3%), and SPG11 (3.3%). Clinical analysis showed that some symptoms were often related to specific subtypes, and rearrangement-related SPG3A patients seemingly had later onset. We observed a presumptive anticipation among SPG4 and SPG3A families due to rearrangement. CONCLUSIONS: Based on the largest known Asian HSP cohort, including the largest subgroup of rearrangement-related pedigrees, we gain a comprehensive understanding of the clinical and genetic spectrum of HSP. We propose a diagnostic flowchart to sequentially detect the causative genes in practice. Large fragment mutations account for a considerable proportion of HSP, and thus, MLPA screening acts as a beneficial supplement to routine WES. © 2024 International Parkinson and Movement Disorder Society.

The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China.

BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R)-related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated. OBJECTIVE: The objective of the study is to clarify the core features and influence factors of CRD patients in China. METHODS: Clinical and genetic-related data of CRD patients in China were collected. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations. RESULTS: A total of 103 patients were included, with a male-to-female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients. CONCLUSIONS: The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society.

Remodeling the Electronic Structure of Metallic Nickel and Ruthenium via Alloying in a Molecular Template for Sustainable Hydrogen Evolution.

The reasonably constructed high-performance electrocatalyst is crucial to achieve sustainable electrocatalytic water splitting. Alloying is a prospective approach to effectively boost the activity of metal electrocatalysts. However, it is a difficult subject for the controllable synthesis of small alloying nanostructures with high dispersion and robustness, preventing further application of alloy catalysts. Herein, we propose a well-defined molecular template to fabricate a highly dispersed NiRu alloy with ultrasmall size. The catalyst presents superior alkaline hydrogen evolution reaction (HER) performance featuring an overpotential as low as 20.6 ± 0.9 mV at 10 mA·cm-2. Particularly, it can work steadily for long periods of time at industrial-grade current densities of 0.5 and 1.0 A·cm-2 merely demanding low overpotentials of 65.7 ± 2.1 and 127.3 ± 4.3 mV, respectively. Spectral experiments and theoretical calculations revealed that alloying can change the d-band center of both Ni and Ru by remodeling the electron distribution and then optimizing the adsorption of intermediates to decrease the water dissociation energy barrier. Our research not only demonstrates the tremendous potential of molecular templates in architecting highly active ultrafine nanoalloy but also deepens the understanding of water electrolysis mechanism on alloy catalysts.

Phenethyl isothiocyanate inhibits metastasis potential of non-small cell lung cancer cells through FTO mediated TLE1 m6A modification.

N6-methyladenosine (m6A) modification is a prevalent RNA epigenetic modification, which plays a crucial role in tumor progression including metastasis. Isothiocyanates (ITCs) are natural compounds and inhibit the tumorigenesis of various cancers. Our previous studies show that ITCs inhibit the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells, and have synergistic effects with chemotherapy drugs. In this study, we investigated the molecular mechanisms underlying the inhibitory effects of ITCs on cancer cell metastasis. We showed that phenethyl isothiocyanate (PEITC) dose-dependently inhibited the cell viability of both NSCLC cell lines H1299 and H226 with IC50 values of 17.6 and 15.2 µM, respectively. Furthermore, PEITC dose-dependently inhibited the invasion and migration of H1299 and H226 cells. We demonstrated that PEITC treatment dose-dependently increased m6A methylation levels and inhibited the expression of the m6A demethylase fat mass and obesity-associated protein (FTO) in H1299 and H226 cells. Knockdown of FTO significantly increased m6A methylation in H1299 and H226 cells, impaired their abilities of invasion and migration in vitro, and enhanced the inhibition of PEITC on tumor growth in vivo. Overexpression of FTO promoted the migration of NSCLC cells, and also mitigated the inhibitory effect of PEITC on migration of NSCLC cells. Furthermore, we found that FTO regulated the mRNA m6A modification of a transcriptional co-repressor Transducin-Like Enhancer of split-1 (TLE1) and further affected its stability and expression. TCGA database analysis revealed TLE1 was upregulated in NSCLC tissues compared to normal tissues, which might be correlated with the metastasis status. Moreover, we showed that PEITC suppressed the migration of NSCLC cells by inhibiting TLE1 expression and downstream Akt/NF-κB pathway. This study reveals a novel mechanism underlying ITC's inhibitory effect on metastasis of lung cancer cells, and provided valuable information for developing new therapeutics for lung cancer by targeting m6A methylation.

Momentary skills use predicts decreased binge eating and purging early in day treatment: An ecological momentary assessment study.

OBJECTIVE: Emerging research indicates that skills acquisition may be important to behavior change in cognitive behavior therapy (CBT) for eating disorders. This study investigated whether skills use assessed in real time during the initial 4 weeks of CBT-based day treatment was associated with momentary eating disorder behavior change and rapid response to treatment. METHODS: Participants with DSM-5 bulimia nervosa or purging disorder (N = 58) completed ecological momentary assessments (EMA) several times daily for the first 28 days of treatment. EMA assessed skills use, the occurrence of binge eating and/or purging, and state negative affect. Rapid response was defined as abstinence from binge eating and/or purging in the first 4 weeks of treatment. RESULTS: Greater real-time skills use overall, and use of "planning ahead," "distraction," "social support," and "mechanical eating" skills in particular, were associated with a lower likelihood of engaging in binge eating or purging during the same period. After controlling for baseline group differences in overall difficulties with emotion regulation, rapid and non-rapid responders did not differ in overall skills use, or skills use at times of higher negative affect, during the EMA period. DISCUSSION: Momentary use of skills appears to play an important role in preventing binge eating and purging, and certain skills appear to be particularly helpful. These findings contribute to the literature elucidating the processes by which CBT treatments for eating disorders work by providing empirical evidence that skills use helps to prevent binge eating and purging behaviors. PUBLIC SIGNIFICANCE: Individuals with eating disorders learn new skills during treatment to help them improve their symptoms. This study shows that for people with eating disorders, using skills helps prevent eating disorder behaviors in the moment. Certain skills may be particularly helpful, including planning ahead, distracting activities, support from others, and focusing on eating meals and snacks regardless of how one is feeling. These findings help us better understand how treatments work.

Effect of esketamine on postoperative analgesia and postoperative delirium in elderly patients undergoing gastrointestinal surgery.

OBJECTIVE: To investigate the analgesic effect of esketamine combined with low-dose sufentanil in elderly patients after gastrointestinal surgery, and whether the anti-inflammatory effect of esketamine is involved in the mechanism of postoperative delirium. METHOD: We enrolled sixty elderly patients (age ≥ 65 years old, American Society of Anesthesiologists (ASA) grade I-III) who underwent gastrointestinal surgery. Patients were randomly assigned to Group C (control group) who received sufentanil 2 ug/kg, and Group E (experimental group) who received sufentanil 1.5 ug/kg + esketamine 1 mg/kg, with 30 patients in each group. All patients underwent total intravenous anesthesia during the surgery and were connected to a patient-controlled intravenous analgesia (PCIA) pump after surgery. The primary outcome was the evaluation of pain at 4, 24, 48 h after surgery which was evaluated by NRS scores. In secondary outcomes, inflammation was assessed by measuring IL-6 levels using ELISA. The postoperative delirium and the occurrence of adverse reactions were observed on the 1st and 3rd day after surgery. RESULTS: The NRS scores at 4, 24, and 48 h after surgery in the experimental group [(4.53 ± 1.22), (3.46 ± 0.73), (1.37 ± 0.99)] were lower than that in the control group [(5.23 ± 1.16), (4.46 ± 0.77), (2.13 ± 0.78)] (P < 0.05). The concentration of serum IL-6 in the experimental group at 24 and 48 h after operation [(15.96 ± 4.65), (11.8 ± 3.24)] were lower than that in the control group [(23.07 ± 4.86), (15.41 ± 4.01)] (P < 0.05); the incidence of postoperative delirium in the experimental group was less than that in the control group (P < 0.05); there was no significant difference in the incidence of postoperative nausea and vomiting between the two groups (P > 0.05), and neither group had nightmares or delirium. CONCLUSION: Esketamine may enhance postoperative pain management compare with sufentanil, and esketamine has anti-inflammatory effects that reduce the incidence of postoperative delirium. TRIAL REGISTRATION: Full name of the registry: Chinese Clinical Trial Registry. TRIAL REGISTRATION NUMBER: ChiCTR2300072374. Date of registration:2023/06/12.