An Injectable Black Phosphorus Hydrogel for Rapid Tooth Extraction Socket Healing.

The excess production of reactive oxygen species (ROS) will delay tooth extraction socket (TES) healing. In this study, we developed an injectable thermosensitive hydrogel (NBP@BP@CS) used to treat TES healing. The hydrogel formulation incorporated black phosphorus (BP) nanoflakes, recognized for their accelerated alveolar bone regeneration and ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator aimed at enhancing angiogenesis. In vivo investigations strongly demonstrated that NBP@BP@CS improved TES healing due to antioxidation and promotion of alveolar bone regeneration by BP nanoflakes. The sustained release of NBP from the hydrogel promoted neovascularization and vascular remodeling. Our results demonstrated that the designed thermosensitive hydrogel provided great opportunity not only for ROS elimination but also for the promotion of osteogenesis and angiogenesis, reflecting the "three birds with one stone" concept, and has tremendous potential for rapid TES healing.

Dual Challenge-Response Systems of a Three-Dimensional "Bionic" Fluorescent Physically Unclonable Function Label.

Inspired by the light and dark variations observed in natural cloud clusters under sunlight, we propose a three-dimensional (3D) "bionic" fluorescent physically unclonable function (PUF) label. The minimalist preparation process eliminates the need for expensive traditional instruments, thus offering new insight into the widespread adoption of 3D PUF labels. The Eu(CCA)3(H2O)2 powder, which is the first to propose its secondary building unit, was chosen as the fluorescent material. Its 3D morphology is preserved in the resin to mimic cloud-like structures. Furthermore, the luminescent properties are elucidated through experimental tests and first-principles calculations. To overcome the coding capacity limitation of traditional two-dimensional (2D) fluorescent PUF labels, a dual challenge-response system model is proposed. The shallow and deep models provide anticounterfeiting information from macro and micro perspectives, respectively. This successfully increases the encoding capacity from 210×10 to 2100×10000 for a 10 × 10 pixel binary code. Therefore, 3D "bionic" fluorescent PUF labels strike a balance between the simple usage of PUF labels and enhanced label security.

Construction and validation of log odds of positive lymph nodes (LODDS)-based nomograms for predicting overall survival and cancer-specific survival in ovarian clear cell carcinoma patients.

Background: Ovarian clear cell carcinoma (OCCC) is one of the special histologic subtypes of ovarian cancer. This study aimed to construct and validate log odds of positive lymph nodes (LODDS)-based nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC. Methods: Patients who underwent surgical treatment between 2010 and 2016 were extracted from the Surveillance Epidemiology and End Results (SEER) database and the data of OCCC patients from the First Affiliated Hospital of Dalian Medical University were used as the external validation group to test the validity of the prognostic model. The best-fitting models were selected by stepwise Cox regression analysis. Survival probability was calculated by the Kaplan-Meier method, and the differences in survival time between subgroups were compared using the log-rank test. Each nomogram's performance was assessed by the calibration plots, decision curve analysis (DCA), and receiver operating characteristics (ROC) curves. Results: T stage, distant metastasis, marital status, and LODDS were identified as significant risk factors for OS. A model with four risk factors (age, T stage, stage, and LODDS value) was obtained for CSS. Nomograms were constructed by incorporating the prognostic factors to predict 1-, 3- and 5-year OS and CSS for OCCC patients, respectively. The area under the curve (AUC) range of our nomogram model for OS and CSS prediction ranged from 0.738-0.771 and 0.769-0.794, respectively, in the training cohort. The performance of this model was verified in the internal and external validation cohorts. Calibration plots illustrated nomograms have good prognostic reliability. Conclusion: Predictive nomograms were constructed and validated to evaluate the OS and CSS of OCCC patients. These nomograms may provide valuable prognostic information and guide postoperative personalized care in OCCC.

Building Haplotype-Resolved 3D Genome Maps of Chicken Skeletal Muscle.

Haplotype-resolved 3D chromatin architecture related to allelic differences in avian skeletal muscle development has not been addressed so far, although chicken husbandry for meat consumption has been prevalent feature of cultures on every continent for more than thousands of years. Here, high-resolution Hi-C diploid maps (1.2-kb maximum resolution) are generated for skeletal muscle tissues in chicken across three developmental stages (embryonic day 15 to day 30 post-hatching). The sequence features governing spatial arrangement of chromosomes and characterize homolog pairing in the nucleus, are identified. Multi-scale characterization of chromatin reorganization between stages from myogenesis in the fetus to myofiber hypertrophy after hatching show concordant changes in transcriptional regulation by relevant signaling pathways. Further interrogation of parent-of-origin-specific chromatin conformation supported that genomic imprinting is absent in birds. This study also reveals promoter-enhancer interaction (PEI) differences between broiler and layer haplotypes in skeletal muscle development-related genes are related to genetic variation between breeds, however, only a minority of breed-specific variations likely contribute to phenotypic divergence in skeletal muscle potentially via allelic PEI rewiring. Beyond defining the haplotype-specific 3D chromatin architecture in chicken, this study provides a rich resource for investigating allelic regulatory divergence among chicken breeds.

Biomimetic nanocarriers loaded with temozolomide by cloaking brain-targeting peptides for targeting drug delivery system to promote anticancer effects in glioblastoma cells.

Glioma is the leading cancer of the central nervous system (CNS). The efficacy of glioma treatment is significantly hindered by the presence of the blood-brain barrier (BBB) and blood-brain tumour barrier (BBTB), which prevent most drugs from entering the brain and tumours. Hence, we established a novel drug delivery nanosystem of brain tumour-targeting that could self-assemble the method using an amphiphilic Zein protein isolated from corn. Zein's amphiphilicity prompted it to self-assembled into NPs, efficiently containing TMZ. This allowed us to investigate temozolomide (TMZ) for glioblastoma (GBM) treatment. To construct TMZ-encapsulated NPs (TMZ@RVG-Zein NPs), the NPs' Zein was clocked to rabies virus glycoprotein 29 (RVG29). To verify that the NPs could penetrate the BBB and precisely target and kill the GBM cancer cell line, in vitro studies were performed. The process of NPs penetrating cancer cell membranes was investigated using enzyme-linked immunosorbent assays (ELISAs) to measure the expressions of nicotinic acetylcholine receptors (nAChRs) on the U87 cell line. Therefore, effective targeted brain cancer treatment is possible by forming NP clocks, a cell-penetrating natural Zein protein with an RVG29. These NPs can penetrate the blood-brain barrier (BBB) and enter the glioblastoma (U87) cell line to release TMZ. These NPs have a distinct cocktail of biocompatibility and brain-targeting abilities, making them ideal for involving brain diseases.

Transcriptomic and metabolomic analysis provides insight into imazethapyr toxicity to non-target plants.

Imazethapyr is a widely used imidazolinone herbicide worldwide, and its potential adverse effects on non-target plants have raised concerns. Understanding the mechanisms of imazethapyr phytotoxicity is crucial for its agro-ecological risk assessment. Here, the comprehensive molecular responses and metabolic alterations of Arabidopsis in response to imazethapyr were investigated. Our results showed that root exposure to imazethapyr inhibited shoot growth, reduced chlorophyll contents, induced photoinhibition and decreased photosynthetic activity. By non-target metabolomic analysis, we identified 75 metabolites that were significantly changed after imazethapyr exposure, and they are mainly enriched in carbohydrate, lipid and amino acid metabolism. Transcriptomic analysis confirmed that imazethapyr significantly downregulated the genes involved in photosynthetic electron transport and the carbon cycle. In detail, 48 genes in the photosynthetic lightreaction and 11 genes in Calvin cycle were downregulated. Additionally, the downregulation of genes related to electron transport in mitochondria provides strong evidence for imazethapyr inhibiting photosynthetic carbon fixation and cellular energy metabolism as one of mechanisms of toxicity. These results revealed the molecular and metabolic basis of imazethapyr toxicity on non-target plants, contributing to environmental risk assessment and mitigate negative impact of imazethapyr residues in agricultural soils.

Giant magnetocaloric effect in spin supersolid candidate Na2BaCo(PO4)2.

Supersolid, an exotic quantum state of matter that consists of particles forming an incompressible solid structure while simultaneously showing superfluidity of zero viscosity1, is one of the long-standing pursuits in fundamental research2,3. Although the initial report of 4He supersolid turned out to be an artefact4, this intriguing quantum matter has inspired enthusiastic investigations into ultracold quantum gases5-8. Nevertheless, the realization of supersolidity in condensed matter remains elusive. Here we find evidence for a quantum magnetic analogue of supersolid-the spin supersolid-in the recently synthesized triangular-lattice antiferromagnet Na2BaCo(PO4)2 (ref. 9). Notably, a giant magnetocaloric effect related to the spin supersolidity is observed in the demagnetization cooling process, manifesting itself as two prominent valley-like regimes, with the lowest temperature attaining below 100 mK. Not only is there an experimentally determined series of critical fields but the demagnetization cooling profile also shows excellent agreement with the theoretical simulations with an easy-axis Heisenberg model. Neutron diffractions also successfully locate the proposed spin supersolid phases by revealing the coexistence of three-sublattice spin solid order and interlayer incommensurability indicative of the spin superfluidity. Thus, our results reveal a strong entropic effect of the spin supersolid phase in a frustrated quantum magnet and open up a viable and promising avenue for applications in sub-kelvin refrigeration, especially in the context of persistent concerns about helium shortages10,11.

Exploring the pathogenesis and key genes associated of acute myocardial infarction complicated with Alzheimer's disease.

Despite mounting evidence linking Acute Myocardial Infarction (AMI) to Alzheimer's disease (AD), the shared mechanism of these two conditions' occurrence remains unclear. This research aims to delve deeper into the molecular process of the occurrence of the two diseases. We retrieved the gene expression profiles of AD (GSE5281) and AMI (GSE66360) from the Gene Expression Omnibus database. Then, a total of 22 common differentially expressed genes (DEGs) including one downregulated gene and 21 upregulated genes were chosen for further analysis. Following the discovery of the common DEGs between AMI and AD, we performed protein-protein interaction analysis and hub gene identification analysis. Next, ten important hub genes were identified. Additionally, the key genes were identified by the least absolute shrinkage and selection operator and support vector machine-recursive feature elimination and multivariable logistic regression analysis. The BCL6 was identified to be the most connected with AMI and AD. Finally, the BCL6 gene was validated in the GSE40680 (AMI) and GSE122063 (AD) datasets. Our research indicates that AMI and AD share a comparable pathophysiology. The Hub genes, especially BCL6, were essential in developing AMI and AD. In addition, these hub genes and shared pathways can offer fresh perspectives for additional mechanism investigation.

High-resolution mass spectrometry-based non-targeted metabolomics reveals toxicity of naphthalene on tall fescue and intrinsic molecular mechanisms.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous at relatively high concentrations by atmospheric deposition, and they are threatening to the environment. In this study, the toxicity of naphthalene on tall fescue and its potential responding mechanism was first studied by integrating approaches. Tall fescue seedlings were exposed to 0, 20, and 100 mg L-1 naphthalene in a hydroponic environment for 9 days, and toxic effects were observed by the studies of general physiological studies, chlorophyll fluorescence, and root morphology. Additionally, Ultra Performance Liquid Chromatography - Electrospray Ionization - High-Resolution Mass Spectrometry (UPLC-ESI-HRMS) was used to depict metabolic profiles of tall fescue under different exposure durations of naphthalene, and the intrinsic molecular mechanism of tall fescue resistance to abiotic stresses. Tall fescue shoots were more sensitive to the toxicity of naphthalene than roots. Low-level exposure to naphthalene inhibited the electron transport from the oxygen-evolving complex (OEC) to D1 protein in tall fescue shoots but induced the growth of roots. Naphthalene induced metabolic change of tall fescue roots in 12 h, and tall fescue roots maintained the level of sphingolipids after long-term exposure to naphthalene, which may play important roles in plant resistance to abiotic stresses.

BRAF - a tumour-agnostic drug target with lineage-specific dependencies.

In June 2022, the FDA granted Accelerated Approval to the BRAF inhibitor dabrafenib in combination with the MEK inhibitor trametinib for the treatment of adult and paediatric patients (≥6 years of age) with unresectable or metastatic BRAFV600E-mutant solid tumours, except for BRAFV600E-mutant colorectal cancers. The histology-agnostic approval of dabrafenib plus trametinib marks the culmination of two decades of research into the landscape of BRAF mutations in human cancers, the biochemical mechanisms underlying BRAF-mediated tumorigenesis, and the clinical development of selective RAF and MEK inhibitors. Although the majority of patients with BRAFV600E-mutant tumours derive clinical benefit from BRAF inhibitor-based combinations, resistance to treatment develops in most. In this Review, we describe the biochemical basis for oncogenic BRAF-induced activation of MAPK signalling and pan-cancer and lineage-specific mechanisms of intrinsic, adaptive and acquired resistance to BRAF inhibitors. We also discuss novel RAF inhibitors and drug combinations designed to delay the emergence of treatment resistance and/or expand the population of patients with BRAF-mutant cancers who benefit from molecularly targeted therapies.

Ethical perspective on AI hazards to humans: A review.

This article explores the potential ethical hazards of artificial intelligence (AI) on society from an ethical perspective. We introduce the development and application of AI, emphasizing its potential benefits and possible negative impacts. We particularly examine the application of AI in the medical field and related ethical and legal issues, and analyze potential hazards that may exist in other areas of application, such as autonomous driving, finance, and security. Finally, we offer recommendations to help policymakers, technology companies, and society as a whole address the potential hazards of AI. These recommendations include strengthening regulation and supervision of AI, increasing public understanding and awareness of AI, and actively exploring how to use the advantages of AI to achieve a more just, equal, and sustainable social development. Only by actively exploring the advantages of AI while avoiding its negative impacts can we better respond to future challenges.

PPARγ agonist treatment reduces fibroadipose tissue in secondary lymphedema by exhausting fibroadipogenic PDGFRα+ mesenchymal cells.

Secondary lymphedema occurs in up to 20% of patients after lymphadenectomy performed for the surgical management of tumors involving the breast, prostate, uterus, and skin. Patients develop progressive edema of the affected extremity due to retention of protein-rich lymphatic fluid. Despite compression therapy, patients progress to chronic lymphedema in which noncompressible fibrosis and adipose tissue are deposited within the extremity. The presence of fibrosis led to our hypothesis that rosiglitazone, a PPARγ agonist that inhibits fibrosis, would reduce fibrosis in a mouse model of secondary lymphedema after hind limb lymphadenectomy. In vivo, rosiglitazone reduced fibrosis in the hind limb after lymphadenectomy. Our findings verified that rosiglitazone reestablished the adipogenic features of TGF-ß1-treated mesenchymal cells in vitro. Despite this, rosiglitazone led to a reduction in adipose tissue deposition. Single-cell RNA-Seq data obtained from human tissues and flow cytometric and histological evaluation of mouse tissues demonstrated increased presence of PDGFRα+ cells in lymphedema; human tissue analysis verified these cells have the capacity for adipogenic and fibrogenic differentiation. Upon treatment with rosiglitazone, we noted a reduction in the overall quantity of PDGFRα+ cells and LipidTOX+ cells. Our findings provide a framework for treating secondary lymphedema as a condition of fibrosis and adipose tissue deposition, both of which, paradoxically, can be prevented with a pro-adipogenic agent.

Association of coffee and caffeine consumption with risk and prognosis of endometrial cancer and its subgroups: a Mendelian randomization.

Background: Previous studies have not established potential causal associations between coffee and caffeine consumption in endometrial cancer (EC) and its subgroups. Therefore, we used a two-sample MR method to assess the causal association between coffee and caffeine consumption and EC risk. We also evaluated the association between these genetically predicted exposures and EC prognosis. Materials and methods: This study used 12 and two independent single-nucleotide polymorphisms (SNPs) associated with coffee and caffeine consumption as instrumental variables at a genome-wide significance level of p < 5 × 10-8. The EC Association Consortium (ECAC) performed a genome-wide association study (GWAS) analysis of 12,906 cases and 108,979 controls. FinnGen Consortium performed a GWAS analysis of 1,967 EC cases and 167,189 controls. The primary technique we employed was inverse-variance weighted, followed by the weighted median, MR-Egger regression, and MR robust adjusted profile score methods. We used the MR pleiotropy residual sum, Outlier test, and MR-Egger regression to assess Outlier and pleiotropic variants. We also conducted a sensitivity analysis through the leave-one-out method. Results: Genetically predicted coffee consumption was not associated with EC and its subgroups in the ECAC, and the association was consistent in the FinnGen consortium. After excluding eight SNPs with confounding factors, the study performed sensitivity analyses, delivering consistent results. We also observed that caffeine consumption was not correlated with EC risk. As confirmed by MR analysis, selected SNPs determined that most do not significantly impact the likelihood of developing EC. Conclusion: Our study indicated no convincing evidence supports coffee and caffeine consumption causing EC or impacting its prognosis. More studies are needed to validate the results.

Effects of low-intensity ultrasound opening the blood-brain barrier on Alzheimer's disease-a mini review.

Due to the complex pathological mechanisms of Alzheimer's disease (AD), its treatment remains a challenge. One of the major difficulties in treating AD is the difficulty for drugs to cross the blood-brain barrier (BBB). Low-intensity ultrasound (LIUS) is a novel type of ultrasound with neuromodulation function. It has been widely reported that LIUS combined with intravenous injection of microbubbles (MB) can effectively, safely, and reversibly open the BBB to achieve non-invasive targeted drug delivery. However, many studies have reported that LIUS combined with MB-mediated BBB opening (LIUS + MB-BBBO) can improve pathological deposition and cognitive impairment in AD patients and mice without delivering additional drugs. This article reviews the relevant research studies on LIUS + MB-BBBO in the treatment of AD, analyzes its potential mechanisms, and summarizes relevant ultrasound parameters.

Characteristics of paraspinal muscle degeneration in patients with adult degenerative scoliosis.

INTRODUCTION: Adult degenerative scoliosis (ADS) is a 3D deformity that greatly affects the quality of life of patients and is closely related to the quality of paraspinal muscles (PSMs), but the specific degenerative characteristics have not been described. METHODS: This study included ADS patients who were first diagnosed in our hospital from 2018 to 2022. Muscle volume (MV) and fat infiltration (FI) of PSM were measured by 3D reconstruction, and spinal parameters were assessed by X-ray. The values of convex side (CV) and concave side (CC) were compared. RESULTS: Fifty patients were enrolled with a mean age of 64.1 ± 5.8 years old. There were significant differences in MV, FI, and Cobb angle between male and female groups. The MV of MF and PS on the CC was significantly larger than that on the CV. In the apex and the segments above the apex, the FI of the MF on the CC is greater than the CV, and in the CV of the segment below the apex, the FI of the MF is greater than the CC. Besides, there was a significant positive correlation between the FI and Cobb angle in the MF of the CC-CV. CONCLUSION: There were significant differences in the MV and FI of PSM on both sides of the spine in ADS patients. It was determined that the PSM of ADS showed different degrees of degeneration in different levels of the lumbar spine and were positively correlated with Cobb angle.

Metabolic syndrome and risk of ovarian cancer: a systematic review and meta-analysis.

Background: MetS is associated with greater morbidity and mortality in relation to a number of malignancies, but its association with ovarian cancer remains contested. The present study was a systematic review and meta-analysis of case-control and cohort studies examining the association between MetS and ovarian cancer risk. Methods: The study was registered on the PROSPERO platform in January 2023 (CRD42023391830). Up until February 13, 2023, a complete search was undertaken in PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials. On the basis of inclusion and exclusion criteria, eligible studies for meta-analysis were screened to determine the association between MetS and ovarian cancer risk. Results: Five studies were included in total, including three cohort studies and two case-control studies. Meta-analysis showed no significant correlation between metabolic syndrome and ovarian cancer (OR=1.29, 95% CI: 0.90-1.84). Significant heterogeneity (I2 = 92.6, P<0.05) existed between the included studies. We performed a subgroup analysis of the risk of bias and showed that only unadjusted stratification of risk of bias for smoking (OR= 3.19, 95% CI: 2.14-4.76) and hysterectomy (OR= 3.19, 95% CI: 2.14-4.76) demonstrated a relationship between metabolic syndrome and ovarian cancer risk. The meta-regression analysis revealed that smoking and hysterectomy excision were substantially linked with heterogeneity (p < 0.05). Conclusion: Our research revealed no statistically significant association between MetS and ovarian cancer risk. The prevalence of metabolic syndrome has highlighted the need of enhancing and controlling women's metabolic health. However, the evaluation of metabolic syndrome as a cancer risk factor may be deceptive and etiologically uninformative.