Injectable hydrogels activated with copper sulfide nanoparticles for enhancing spatiotemporal sterilization and osteogenesis in periodontal therapy.

Developing biomaterials capable of promoting bone regeneration in bacteria-infected sites is of utmost urgency for periodontal disease therapies. Here we produce a hybrid hydrogel by integrating CuS nanoparticles (CuSNPs), which could kill bacteria through photothermal therapy (PTT) triggered by a near infrared (NIR) light, and a gelatin methacryloyl (GelMA) hydrogel, which is injectable and biocompatible. Specifically, CuSNPs were precipitated by chitosan (CS) firstly, then grafted with methacrylic anhydride (MA) to form CuSNP@CS-MA, which was photo-crosslinked with GelMA to synthesize hybrid hydrogels (GelMA/CuSNP). The hybrid hydrogels exhibited a broad-spectrum antibacterial property that could be spatiotemprorally manipulated through applying a NIR light. Their mechanical properties were adjustable by controlling the concentration of CuSNPs, enabling the hydrogels to become more adapted to the oral diseases. Meanwhile, the hybrid hydrogels showed good cytocompatibility in vitro and improved hemostasis in vivo. Moreover, they accelerated alveolar osteogenesis and vascular genesis, successfully treating periodontis in four weeks in a rat model. GelMA/CuSNP hydrogels showed a broad-spectrum sterilization ability via PTT in vitro and outstanding antibacterial property in vivo, suggesting that the hybrid hydrogels could function in the challenging, bacteria-rich, oral environment. Such injectable hybrid hydrogels, capable of achieving both facilitated osteogenesis and NIR-inducible sterilization, represent a new biomaterial for treating periodontitis.

Ideal cardiovascular health index and high-normal blood pressure in elderly people: evidence based on real-world data.

Limited information is available on the cardiovascular health (CVH) index and risk of high-normal blood pressure (HNBP) in elderly people. Randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used in this study analyze the relationship between CVH index and HNBP in the elderly. 1089 non-hypertensive residents aged 65 years or older completed the study. The positive rate of HNBP was 75.85% (male vs. female: 76.13% vs. 75.64%, P = 0.852); The ideal rate of CVH (ideal CVH index ≥ 5 items) was 14.51% (male vs. female: 15.91% vs. 13.46%, P = 0.256). Compared with people with 0-2 ideal CVH index, the risk of HNBP in people with 4 ideal indexes and ≥ 5 ideal indexes decreased by 50% and 63%, respectively, and their OR (95% CI) were 0.50 (0.31, 0.81) and 0.37 (0.21, 0.66), respectively. The results of the trend test showed that the risk of HNBP decreased by 32% for every increase in the ideal CVH index (trend P < 0.001) and TyG index does not play a mediating role in this relationship. That is, increasing the number of ideal CVH index may effectively reduce the risk of HNBP in elderly by one-third.

A DNA tetrahedron-based nanosuit for efficient delivery of amifostine and multi-organ radioprotection.

Unnecessary exposure to ionizing radiation (IR) often causes acute and chronic oxidative damages to normal cells and organs, leading to serious physiological and even life-threatening consequences. Amifostine (AMF) is a validated radioprotectant extensively applied in radiation and chemotherapy medicine, but the short half-life limits its bioavailability and clinical applications, remaining as a great challenge to be addressed. DNA-assembled nanostructures especially the tetrahedral framework nucleic acids (tFNAs) are promising nanocarriers with preeminent biosafety, low biotoxicity, and high transport efficiency. The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity. We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection (tFNAs@AMF, also termed nanosuit). By establishing the mice models of accidental total body irradiation (TBI) and radiotherapy model of Lewis lung cancer, we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress. In the accidental total body irradiation (TBI) mice model, the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents, and functional recovery of hematopoietic system, reducing IR-induced pathological damages of multi-organ and safeguarding mice from lethal radiation. More importantly, the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer. Based on a conveniently available DNA tetrahedron-based nanocarrier, this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs. Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.

Structural studies of intrinsically disordered MLL-fusion protein AF9 in complex with peptidomimetic inhibitors.

AF9 (MLLT3) and its paralog ENL(MLLT1) are members of the YEATS family of proteins with important role in transcriptional and epigenetic regulatory complexes. These proteins are two common MLL fusion partners in MLL-rearranged leukemias. The oncofusion proteins MLL-AF9/ENL recruit multiple binding partners, including the histone methyltransferase DOT1L, leading to aberrant transcriptional activation and enhancing the expression of a characteristic set of genes that drive leukemogenesis. The interaction between AF9 and DOT1L is mediated by an intrinsically disordered C-terminal ANC1 homology domain (AHD) in AF9, which undergoes folding upon binding of DOT1L and other partner proteins. We have recently reported peptidomimetics that disrupt the recruitment of DOT1L by AF9 and ENL, providing a proof-of-concept for targeting AHD and assessing its druggability. Intrinsically disordered proteins, such as AF9 AHD, are difficult to study and characterize experimentally on a structural level. In this study, we present a successful protein engineering strategy to facilitate structural investigation of the intrinsically disordered AF9 AHD domain in complex with peptidomimetic inhibitors by using maltose binding protein (MBP) as a crystallization chaperone connected with linkers of varying flexibility and length. The strategic incorporation of disulfide bonds provided diffraction-quality crystals of the two disulfide-bridged MBP-AF9 AHD fusion proteins in complex with the peptidomimetics. These successfully determined first series of 2.1-2.6 Å crystal complex structures provide high-resolution insights into the interactions between AHD and its inhibitors, shedding light on the role of AHD in recruiting various binding partner proteins. We show that the overall complex structures closely resemble the reported NMR structure of AF9 AHD/DOT1L with notable difference in the conformation of the ß-hairpin region, stabilized through conserved hydrogen bonds network. These first series of AF9 AHD/peptidomimetics complex structures are providing insights of the protein-inhibitor interactions and will facilitate further development of novel inhibitors targeting the AF9/ENL AHD domain.

Investigation of ENO2 as a promising novel marker for the progression of colorectal cancer with microsatellite instability-high.

BACKGROUND: Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. METHODS: Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. RESULTS: This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. CONCLUSION: Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.

Gender Impacted Gut Microbiota and Growth Performance in the Blotched Snakehead (Channa maculata).

The blotched snakehead Channa maculata is an important economical freshwater species in East Asia. However, there has been relatively little research conducted on the correlation between gender and gut microbes. In this study, 36 of 1000 blotched snakeheads were randomly selected for growth performance measurement and gut microbiota high-throughput sequencing. Results showed that microbial diversity, composition, and metabolic functions were altered by gender and growth performance except the microbial network. In our study, Proteobacteria were the most abundant phylum, with Fusobacteria showing enrichment in males and Bacteroidetes in females. Notably, phylum Deinococcus-Thermus was identified as a significant biomarker. The Cetobacterium was the most abundant genus-level taxon. Furthermore, gut microbes specializing in the production of gut-healthy substances, such as coenzymes and vitamins, were identified as biomarkers in the fast-growing group. Our investigation highlighted the impact of gender on the composition and abundance of gut microbial biomarkers in both males and females, thereby influencing differential growth performance through the modulation of specific metabolic functions.

Unveiling the impact of microplastics with distinct polymer types and concentrations on tidal sediment microbiome and nitrogen cycling.

Microplastics (MPs) are distributed widely in the ocean surface waters and sediments. Increasing MPs contamination in intertidal zone profoundly impacts microbial ecosystem services and biogeochemical process. Little is known about the response of tidal sediment microbiome to MPs. We conducted a 30-day laboratory microcosm study using five polymers (PE, PBS, PC, PLA and PET) at three concentrations (1 %, 2 % and 5 %, w/w). High throughput sequencing of 16 S rRNA, qPCR and enzyme activity test were applied to demonstrate the response of microbial community and nitrogen cycling functional genes to MPs. MPs reduced the microbial alpha diversity and the microbial dissimilarity while the effects of PLA-MPs were concentration dependent. LEfSe analysis indicated that the Proteobacteria predominated for all MP treatments. Mantel's test, RDA and correlation analysis implied that pH may be the key environmental factor for causing microbial alterations. MPs enhanced nitrogen fixation in tidal sediment. PLA levels of 1 % but not 5 % produced the most significant effects in nitrogen cycling functional microbiota and genes. PLS-PM revealed that impacts of MPs on tidal sediment microbial communities and nitrogen cycling were dominated by indirect effects. Our study deepened understanding and filled the knowledge gap of MP contaminants affecting tidal sediment microbial nitrogen cycling.

Dose finding for ZSP1601 in patients with nonalcoholic steatohepatitis using population pharmacokinetics and exposure-response approach.

INTRODUCTION: ZSP1601 is a novel pan-phosphodiesterase inhibitor developed in China specifically for the treatment of nonalcoholic fatty liver disease (NAFLD). AIM: The aim is to develop a population pharmacokinetic (pop PK) model for ZSP1601 by integrating data from two clinical studies. This undertaking aims to deepen our understanding of the clinical factors that influence ZSP1601 exposure while simultaneously investigating exposure-response (ER) relationships related to efficacy and safety. The goal is to guide formulating optimal dosage strategies in the subsequent phases of clinical trials. METHODS: Analysis of pooled concentration-time data from 95 subjects, with 2647 observations from two clinical trials involving healthy volunteers and NAFLD patients, employed a nonlinear mixed-effects modeling approach to characterize ZSP1601 pharmacokinetics. Covariate impact on ZSP1601 pharmacokinetics was investigated, and relationships between ZSP1601 exposure, efficacy and safety endpoints were explored. RESULTS: A two-compartment model featuring sequential zero-order then first-order absorption and first-order elimination effectively described ZSP1601's pharmacokinetic profile. Covariate analyses identified body weight as a statistically significant factor affecting drug central volume, while FED (food consumption) influenced absorption rate constant and duration. The Sigmoid Emax model aptly captured exposure-response relationships for ALT (alanine aminotransferase), AST (aspartate aminotransferase), and LFC (liver fat content) percentage changes relative to baseline and ZSP1601 exposure levels (AUCss) on the 29th day. ZSP1601 exposure levels (Cmax1) exhibited a significant exposure-response relationship with headaches (p < 0.001). CONCLUSION: The PopPK model and ER analysis, based on available data, comprehensively characterizes ZSP1601's pharmacokinetic, safety and efficacy profile, aiding informed decisions regarding dosage selection for the drug's complete developmental trajectory. The exposure-response (ER) analysis yields quantitative insights into the optimal balance of efficacy and safety within different dosage regimens for patient administration. In light of these findings, the dose regimen of 100 mg administered twice daily is proposed for subsequent clinical investigations.

Endoscopic Balloon Dilatation of the Eustachian Tube via the Soft Palate Approach in Miniature Pigs.

The eustachian tube (ET) is one of the most complex organs in the human body, and its dysfunction may lead to a variety of diseases. In recent years, an increasing number of scholars have opted to conduct ET-related studies using large experimental animals such as miniature pigs or sheep, yielding promising results. Typically, conventional endoscopic procedures are performed through the nasal approach for large experimental animals. However, due to the elongated and narrow nasal cavity in these animals, transnasal surgeries are challenging. To address this issue, we explored an ET surgery approach via the soft palate. The animal was placed in a supine position. After endotracheal intubation under general anesthesia, a mouth opener was used to fully expose the upper palate. Local infiltration with diluted adrenal fluid was performed for anesthesia of the area. A sickle knife was then used to make a longitudinal soft palate incision at the junction of the soft and hard palates. After hemostasis, an endoscope was inserted into the nasopharynx cavity, allowing the visualization of the pharyngeal opening of the ET on the posterior lateral wall of the nasal cavity. Subsequently, a specialized pusher was used to insert a balloon into ET. The balloon was inflated, maintained at 10 bar for 2 min, and then removed. The incision in the soft palate was then sutured to ensure proper alignment. The soft palate healed well after the operation. This surgical approach is suitable for ET-related procedures in large experimental animals (e.g., miniature pigs, sheep, and dogs). The surgical procedure is simple, with a short surgical time, and wound healing is rapid. Under endoscopy, the pharyngeal opening of the ET is visible, and it is thus a good choice for procedures such as balloon dilation of the ET.

Efficient gold recovery by a thiazolyl covalent organic framework.

Here, we report a thiazoyl covalent organic framework, namely ECUT-COF-29, for gold recovery. Under visible light irradiation, this material can reduce Au3+ to Au0 in a short time, and the adsorption capacity is as high as 3714 mg g-1, showing great potential in gold recovery.

Revisiting the hydrological legacy of revegetation on China's Loess Plateau using Eagleson's ecohydrological perspective.

Revegetation has resulted in a trend of increasing vegetation greenness on the Chinese Loess Plateau. However, it remains unclear whether the regional vegetation coverage exceeds hydroclimatic limitations in the context of revegetation, and the hydrological effects of greening are controversial. Eagleson's optimality hypothesis can explain some of the hydrological effects on the Loess Plateau. Here, building on previous research, the geospatial vegetation states were estimated for pre- and post-revegetation periods on the Loess Plateau from 1982 to 2015 using Eagleson's ecological optimality theory. Additionally, a drought composite analysis approach was utilized to investigate the hydrological effects related to drought (including sensitivity and partitioning) under various vegetation states. It was found that revegetation increased the proportion of catchments in the equilibrium state and decreased the proportion in the disturbed state, owing to a wetter climate compared with the pre-revegetation period. Root-zone soil drought, driven by precipitation (P) deficit, asymmetrically triggered hydrological effects for both the pre- and post-revegetation periods, with reduced runoff (Q) for both periods and a decrease in evapotranspiration (ET) during the pre-revegetation period but an increase in ET during the post-revegetation period. Moreover, catchments in an equilibrium state exhibited lower sensitivity between ET and P, and more stable partitioning of ET with regards to P, compared with those in a disturbed state. These results underscore the theoretical framework that an equilibrium state is crucial for maintaining ecosystem ET. Our results highlight the necessity of considering the hydrologic regulation of vegetation states when assessing the hydrological effects of vegetation change.

USP5 promotes tumorigenesis by activating Hedgehog/Gli1 signaling pathway in osteosarcoma.

Changes in protein ubiquitination have been linked to cancer. Deubiquitinating enzymes (DUBs) counteract E3 ligase activities and have emerged as promising targets for cancer treatment. Ubiquitin-specific peptidase 5 (USP5) is a member of the DUBs family and has been implicated in promoting tumorigenesis in numerous cancers. However, the clinical significance and biological function of USP5 in osteosarcoma (OS) remains unclear. Here, we found elevated USP5 expression in OS tissues compared with normal bone tissues. Furthermore, we observed significant associations of elevated USP5 levels with increased mortality and more malignant phenotypes in OS patients. Moreover, our results revealed that USP5 could facilitate metastasis and cell progression in OS by activating the hedgehog (Hh) signaling pathway using cultured cells and animal tumor models. Mechanistically, USP5 appeared to stabilize and deubiquitinate Gli1, a key mediator of the Hh signaling pathway. Additionally, the oncogenic effect of USP5 in OS was dependent on Gli1 stability. Our findings support the model where USP5 contributes to OS pathogenesis by activating the Hh/Gli1 signaling pathway, making USP5 a potential diagnostic and therapeutic target for OS.

Diagnosis and management of intraspinal tuberculoma with osseous involvement: a case report.

Introduction and importance: Intraspinal tuberculoma is rare and challenging situation, which results in serious neurological dysfunctions. Case presentation: This case report shows an intraspinal tuberculoma with osseous involvement in a 31-year-old male patient with subacute progressing neurologic deficit. His medical history included tuberculosis of pulmonary and intestinal 8 years previously, at which time he had been treated with intestinal obstruction operation and antituberculosis treatment. A quadruple antituberculosis treatment was carried out after admission; however, his neurological condition was steadily worsening. He underwent debulking of mass for decompression and pathological analysis revealed intraspinal tuberculoma. The patient was prescribed a 12-month course of antituberculosis therapy, and a good clinical outcome was obtained subsequently. Clinical discussion: This case was treated by microsurgical resection and antituberculosis therapy, and the outcome was favourable. Conclusion: Intraspinal tuberculoma should be considered when an intraspinal mass is found with a history of tuberculosis, it can be effectively diagnosed by MRI and treated by the combination of medical and surgical treatments.

Effects of the ferroptosis inducer erastin on osteogenic differentiation and biological pathways of primary osteoblasts.

BACKGROUND: Periodontitis is a chronic destructive inflammatory disease exacerbated by osteoblast dysfunction. Ferroptosis has emerged as a significant factor that could contribute to the pathological changes observed in periodontitis. However, the impact of ferroptosis on osteogenic differentiation and gene expression patterns of primary osteoblasts remain elusive. METHODS: In this study, osteoblasts were osteogenically induced for specific durations with and without the ferroptosis inducer erastin. Subsequently, cell proliferation, ferroptosis-related molecules, and osteogenic differentiation capacity were assessed. Furthermore, the differences in transcriptome expression following erastin treatment were analyzed by RNA sequencing. RESULTS: The results demonstrated that erastin treatment induced ferroptosis, resulting in suppressed cell proliferation and impaired osteogenic differentiation. Transcriptomic analysis revealed significant alterations in processes such as hydrogen peroxide catabolism, response to lipid peroxidation, and metal iron binding, as well as BMP receptor activity and collagen type XI trimer. CONCLUSION: The ferroptosis inducer erastin inhibited osteoblast proliferation and differentiation. Our study provides novel insights into the effect of ferroptosis on osteogenesis, suggesting that targeting ferroptosis may present a promising approach in the treatment of periodontitis.

High-reliability infrared broadband thin-film polarizing beam splitter with ZnSe compensation layers.

Thin-film polarizing beam splitters (PBSs) fulfill a pivotal role in laser beam splitting, modulation, shaping and isolation. In this study, a high-reliability infrared broadband thin-film PBS was developed. To correct for tensile stress in Ge/YbF3 multilayer coatings, ZnSe compensation layers were incorporated in the multilayer design. The effects of different symmetrical periods on the spectral properties of the infrared PBS were systematically discussed. The infrared PBS operated at 45° and in the long-wave infrared (LWIR) band. Using the percent of optical extrema monitoring (POEM) strategy combined with the high-temperature optical constants (HTOC) of Ge film, the infrared PBS was precisely fabricated on ZnSe substrates. Subsequently, the spectral performance and film reliability of the infrared PBS were carefully characterized. Specifically, the transmittance of p-polarization surpassed 96%, while the extinction ratio exceeded 100:1 within the 10.6 ± 0.15 µm band. The infrared PBS demonstrated commendable environmental reliability, in addition to exhibiting excellent spectral characteristics.

Wavelength division multiplexing based on the coupling effect of helical edge states in two-dimensional dielectric photonic crystals.

Photonic topological insulators with topologically protected edge states featuring one-way, robustness and backscattering-immunity possess extraordinary abilities to steer and manipulate light. In this work, we construct a topological heterostructure (TH) consisting of a domain of nontrivial pseudospin-type topological photonic crystals (PCs) sandwiched between two domains of trivial PCs based on two-dimensional all-dielectric core-shell PCs in triangle lattice. We consider three THs with different number of layers in the middle nontrivial domain (i.e., one-layer, two-layer, three-layer) and demonstrate that the projected band diagrams of the three THs host interesting topological waveguide states (TWSs) with properties of one-way, large-area, broad-bandwidth and robustness due to coupling effect of the helical edge states associated with the two domain-wall interfaces. Moreover, taking advantage of the tunable bandgap between the TWSs by the layer number of the middle domain due to the coupling effect, a topological Y-splitter with functionality of wavelength division multiplexing is explicitly demonstrated exploiting the unique feature of the dispersion curves of TWSs in the three THs. Our work not only offers a new method to realize pseudospin-polarized large-area TWSs with tunable mode-width, but also could provide new opportunities for practical applications in on-chip multifunctional (i.e., wavelength division multiplexing) photonic devices with topological protection and information processing with pseudospin-dependent transport.

A network meta-analysis on the effects of different exercise types on COPD patients.

Objective: This study aimed to compare and rank the effects of aerobic exercise (AE), resistance training (RT), endurance training (ET), and high-intensity interval training (HIIT) in chronic obstructive pulmonary disease (COPD) by network meta-analysis (NMA).Methods: PubMed, Cochrane, Embase, and Web of Science were searched to identify randomized controlled trials investigating the effects of exercise training on COPD. The search period began on the date of database establishment and ended in April 8, 2023. Two reviewers independently screened the retrieved articles, extracted relevant data, and assessed the risk of bias in the included studies. NMA was performed using Stata 15.1 and R 4.2.1.Results: This study included a total of 27 studies involving 1415 patients. The NMA findings indicated that HIIT was the most effective intervention for improving 6-Minute Walk Distance (6MWD) with a SUCRA (Surface Under the Cumulative Ranking) score of 87.68%. In addition, HIIT showed the highest efficacy in improving Forced Expiratory Volume in 1 second (FEV1) with a SUCRA score of 73.17%, FEV1/FVC% with a SUCRA score of 79.52%, and St. George's Respiratory Questionnaire (SGRQ) score with a SUCRA score of 73.88%. Conversely, ET was found to be the most effective for ameliorating Forced Vital Capacity (FVC) with a SUCRA score of 73.39%.Conclusion: The findings of this study suggest that HIIT may be more effective than endurance exercise, resistance exercise, and AE in improving the 6MWD, FEV1, FEV1/FVC ratio, and SGRQ scores in patients with COPD. Additionally, ET may be better than resistance exercise, AE, and HIIT in improving FVC in COPD patients. However, due to the limited number of studies conducted on HIIT, more high-quality randomized controlled trials (RCTs) are required to verify these conclusions.

Sedentary behavior, physical activity, sleep duration and obesity risk: Mendelian randomization study.

BACKGROUND: Observational studies have suggested associations between sedentary behaviors (SB), physical activity (PA), sleep duration (SD), and obesity, but the causal relationships remain unclear. METHODS: We used Mendelian randomization (MR) with genetic variation as instrumental variables (IVs) to assess the causality between SB/PA/SD and obesity. Genetic variants associated with SB/PA/SD were obtained from Genome-wide association study (GWAS), and obesity data came from FinnGen. The primary MR analysis used the instrumental variable weighted (IVW) method, with sensitivity tests including Cochran Q, MR-Egger intercepts, and MR-Radial. Expression Quantitative Trait Loci (eQTL) analysis was applied to identify significant genetic associations and biological pathways in obesity-related tissues. RESULTS: The MR analysis revealed causal relationships between four SB-related lifestyle patterns and obesity. Specifically, increased genetic liability to television watching (IVW MR Odds ratio [OR] = 1.55, [95% CI]:[1.27, 1.90], p = 1.67×10-5), computer use ([OR] = 1.52, [95% CI]:[1.08, 2.13], p = 1.61×10-2), leisure screen time (LST) ([OR] = 1.62, [95% CI] = [1.43, 1.84], p = 6.49×10-14, and driving (MR [OR] = 2.79, [95% CI]:[1.25, 6.21], p = 1.23×10-2) was found to increase the risk of obesity. Our findings indicate that no causal relationships were observed between SB at work, sedentary commuting, PA, SD, and obesity. The eQTL analysis revealed strong associations between specific genes (RPS26, TTC12, CCDC92, NICN1) and SNPs (rs10876864, rs2734849, rs4765541, rs7615206) in both subcutaneous and visceral adipose tissues, which are associated with these SBs. Enrichment analysis further revealed that these genes are involved in crucial biological pathways, including cortisol synthesis, thyroid hormone synthesis, and insulin secretion. CONCLUSIONS: Our findings support a causal relationship between four specific SBs (LST, television watching, computer use, driving) and obesity. These results provide valuable insights into potential interventions to address obesity effectively, supported by genetic associations in the eQTL and enrichment analysis. Further research and public health initiatives focusing on reducing specific SBs may be warranted.

Polymerized carbon dots with high electrochemiluminescence efficiency and long wavelength ECL emission for ultrasensitive detection of MicroRNA-222.

Herein, a new electrochemiluminescence (ECL) biosensor was constructed with highly efficient polymerized carbon dots (PCDs) as ECL emitter and the improved localized catalytic hairpin assembly (L-CHA) as signal amplifier for ultrasensitive detection of microRNA-222 (miRNA-222). Impressively, compared to the traditional carbon dots with inefficient blue region ECL emission, PCDs with N, O co-dope and large conjugated π-system showed high electrical conductivity, narrow band gap and strong radiative transition, which could exhibit high ECL efficiency to improve the sensitivity of detection and long wavelength ECL emission to achieve deep tissue penetration for reducing biological damage. Furthermore, the trace target miRNA-222 could be efficiently converted into large amounts of output DNA labelled with the quencher dopamine (S-DA) through the L-CHA reaction to significantly enhance the target amplification efficiency for further improving the sensitivity of detection. Thus, the ECL biosensor could achieve the ultrasensitive detection of miRNA-222 from 100 aM to 100 pM with the detection limit of 76 aM. Therefore, this work proposed a novel CDs with high ECL efficiency and long wavelength ECL emission, which not only was used to build an ultrasensitive biosensor for biomolecules detection in clinical diagnosis, but also served as a potential emitter for ECL bioimaging.