The BET PROTAC inhibitor GNE-987 displays anti-tumor effects by targeting super-enhancers regulated gene in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. METHODS: We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. RESULTS: In this study, we found that extremely low concentrations of GNE-987(2-10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. CONCLUSIONS: This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Radiological Features of Primary Pulmonary Invasive Mucinous Adenocarcinoma Based on 312 Consecutive Patients.

BACKGROUND: The aim of this study is to investigate the radiological features of primary pulmonary invasive mucinous adenocarcinoma (IMA) in a relatively large population to help improve its further understanding and its accuracy of initial diagnosis. METHODS: This retrospective study included consecutive patients with pathologically confirmed primary pulmonary IMA from January 2019 to December 2021. According to tumor morphology, IMAs were divided into regular nodule/mass, irregular, and large consolidative types. According to tumor density, IMAs were divided into solid, halo, part-solid, pure ground-glass, and cystic types. ANOVA, chi-square, or Fisher exact tests were used to analyze the differences in radiological and clinicopathological characteristics of IMA according to morphological and density subtypes. RESULTS: We analyzed 312 patients. Pulmonary IMA tended to occur in the elderly, with a slightly higher number of women than men. IMA showed a predominance in the lower lobe and adjacent to pleura. IMA of regular nodule/mass, irregular, and large consolidative types accounted for 80.8% (252/312), 13.8% (43/312), and 5.4% (17/312), respectively. Solid, halo, part-solid, pure ground-glass, and cystic IMAs accounted for 55.8% (174/312), 28.2% (88/312), 11.2% (35/312), 1.3% (4/312), and 3.5% (11/312), respectively. The lobulated (76.9%), spiculated (63.5%), and air bronchogram (56.7%) signs were common in IMA. Dead branch sign (88.2%), angiogram sign (88.2%), and satellite nodules/skipping lesions (47.1%) were common in large-consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations were common (56.1%), whereas epidermal growth factor receptor mutations were relatively rare (2.3%). CONCLUSIONS: Pulmonary IMA of regular nodule/mass type and solid type were the most common at the initial diagnosis. Detailed radiological features can aid in the differential diagnosis of IMA.

Identification of hub genes associated with neutrophils in chronic rhinosinusitis with nasal polyps.

Neutrophil infiltration plays a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, pertinent mechanisms remain poorly elucidated. Here, we obtained the data from gene expression omnibus (GEO) and gene set enrichment analysis (GSEA) to identify and validate neutrophil-associated hub genes in CRSwNP. We found that four neutrophil-associated hub genes, namely ICAM1, IL-1ß, TYROBP, and BCL2A1, were markedly upregulated and positively correlated with neutrophil infiltration levels in patients with CRSwNP. Subsequently, this was confirmed by real-time quantitative PCR. In conclusion, we identified the role of neutrophil infiltration in the pathophysiology of CRSwNP, which may be the potential targets for the diagnosis and treatment of CRSwNP.

Impact of corticosteroids on initiation and half-year durability of humoral response in COVID-19 survivors.

Background: The impact of corticosteroids on humoral responses in coronavirus disease 2019 (COVID-19) survivors during the acute phase and subsequent 6-month period remains unknown. This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset. Methods: We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020, which involved adults hospitalized with severe COVID-19 (LOTUS, ChiCTR2000029308). Antibody samples were collected from 192 patients during hospitalization, and kinetic antibodies were monitored at all available time points after recruitment. Additionally, plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit. The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group. Results: From illness onset to day 30, the median antibody titre areas under the receiver operating characteristic curve (AUCs) of nucleoprotein (N), spike protein (S), and receptor-binding domain (RBD) immunoglobulin G (IgG) were significantly lower in the corticosteroids group. The AUCs of N-, S-, and RBD-IgM as well as neutralizing antibodies (NAbs) were numerically lower in the corticosteroids group compared with the non-corticosteroid group. However, peak titres of N, S, RBD-IgM and -IgG and NAbs were not influenced by corticosteroids. During 6-month follow-up, we observed a delayed decline for most binding antibodies, except N-IgM (ß -0.05, 95% CI [-0.10, 0.00]) in the corticosteroids group, though not reaching statistical significance. No significant difference was observed for NAbs. However, for the half-year seropositive rate, corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-, S-, and RBD-IgG or NAbs. Additionally, corticosteroids group showed a trend towards delayed viral clearance compared with the non-corticosteroid group, but the results were not statistically significant (adjusted hazard ratio 0.71, 95% CI 0.50-1.00; P = 0.0508). Conclusion: Our findings suggested that corticosteroid therapy was associated with impaired initiation of the antibody response but this did not compromise the peak titres of binding and neutralizing antibodies. Throughout the decay phase, from the acute phase to the half-year follow-up visit, short-term and low-dose corticosteroids did not significantly affect humoral responses, except for accelerating the waning of short-lived antibodies.

Mapping and Characterization of Local Structures of CsPbBr3.

Inorganic perovskite CsPbBr3 is a promising material for optoelectronic applications and high-energy radiation detection due to its excellent photophysical properties, high carrier mobility, large carrier diffusion length, and higher stability than organic perovskite materials. Understanding phase transitions at the atomic level is crucial for optimizing its applications. Here, we employ experimental characterizations and molecular dynamics simulations to study the phase transitions in CsPbBr3 as a function of temperature. The simulation results are compared with the experimental results, which include X-ray diffraction (XRD). Our simulations provide new insights into the electronic structure and dynamic behavior of the Cs, Pb, and Br atoms as a function of temperature. We observe distinct phase transitions from monoclinic to cubic and analyze the associated changes in the local environment through atomic density contour maps. Our analysis of the atomic density distributions of the Pb, Br, and Cs atoms provides information about the crystal symmetry as a function of temperature. The tilt and rotation angles of [PbBr6] octahedra are increasing with the temperature increase and are found nonzero above 410 K when the structure is cubic, exhibiting the presence of dynamic tilting. Overall, our findings shed light on the thermal stability and structural dynamics of CsPbBr3, contribute to the fundamental understanding of its phase behavior, and provide a crucial pivot for guiding the design of next-generation optoelectronic and radiation detection devices.

A prediction model based on computed tomography characteristics for identifying malignant from benign sub-centimeter solid pulmonary nodules.

Background: Distinguishing benign from malignant sub-centimeter solid pulmonary nodules (SSPNs) continues to be challenging in clinical practice. Earlier diagnosis is crucial for improving patient survival and prognosis. This study aimed to investigate the risk factors of malignant SSPNs and establish and validate a prediction model based on computed tomography (CT) characteristics to assist in their early diagnosis. Methods: A total of 261 consecutive participants with 261 SSPNs were retrospectively recruited between January 2012 and July 2023 from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Center 1), including 161 malignant lesions and 100 benign lesions. Patients were randomly assigned to the training set (n=183) and validation set (n=78) according to a 7:3 ratio. Malignant nodules were confirmed by pathology; and benign nodules were confirmed by follow-up or pathology. Clinical data and CT features were collected to estimate the independent predictors of malignancy of SSPN with multivariate logistic analysis. A clinical prediction model was subsequently established by logistic regression. Furthermore, an additional 69 consecutive patients with 69 SSPNs from The Fourth Hospital of Hebei Medical University (Center 2) between January 2022 and December 2022 were retrospectively included as an external cohort to validate the predictive efficacy of the model. The performance of the prediction model was assessed by sensitivity, specificity, and the area under the receiver operating characteristic curve. Results: There were 113 (61.7%), 48 (61.5%) and 28 (40.6%) malignant SSPNs in the training, internal and external validation sets, respectively. Multivariate logistic analysis revealed four independent predictors of malignant SSPNs: tumor-lung interface (P=0.002), spiculation (P=0.04), air bronchogram (P=0.047), and invisible at the mediastinal window (P=0.003). The area under the curve (AUC) for the prediction model in the training set was 0.875 [95% confidence interval (CI): 0.818, 0.933]; and the sensitivity and specificity were 94.7% and 68.6%, respectively. The AUCs in the internal and external validation set were (0.781; 95% CI: 0.664, 0.897) and (0.873; 95% CI: 0.791, 0.955), respectively; the sensitivity and specificity were 66.7% and 83.3% for the internal validation data, and 100.0% and 61.0% for the external validation data, respectively. Conclusions: The prediction model based on CT characteristics could be helpful for distinguishing malignant SSPNs from benign ones.

Observation of spectral splitting of whispering-gallery modes in asymmetrical photonic molecules.

This Letter investigates mode splitting via whispering gallery modes (WGMs) in asymmetrical photonic molecules (PMs) composed of size-mismatched dual microspheres fabricated from fused silica. The characteristics of asymmetrical PMs were analyzed both numerically and experimentally, focusing specifically on the separation and intensity differences of splitting peaks. The splitting spectra exhibited a redshift, and the separation of two splitting peaks reached a maximum in symmetrical PMs, with a minimal difference in intensity also observed. It was noted that the splitting peaks shifted in opposite directions for the same PMs when coupling points with the tapered fibers were varied. This phenomenon can be applied to select similarly sized microparticles and to recognize PMs in optical devices.

MASS cohort: Multicenter, longitudinal, and prospective study of the role of microbiome in severe pneumonia and host susceptibility.

The MASS cohort comprises 2000 ICU patients with severe pneumonia, covering community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, sourced from 19 hospitals across 10 cities in three provinces. A wide array of samples including bronchoalveolar lavage fluid, sputum, feces, and whole blood are longitudinally collected throughout patients' ICU stays. The cohort study seeks to uncover the dynamics of lung and gut microbiomes and their associations with severe pneumonia and host susceptibility, integrating deep metagenomics and transcriptomics with detailed clinical data.

ALOX5 contributes to glioma progression by promoting 5-HETE-mediated immunosuppressive M2 polarization and PD-L1 expression of glioma-associated microglia/macrophages.

BACKGROUND: Oxylipin metabolism plays an essential role in glioma progression and immune modulation in the tumor microenvironment. Lipid metabolic reprogramming has been linked to macrophage remodeling, while the understanding of oxylipins and their catalyzed enzymes lipoxygenases in the regulation of glioma-associated microglia/macrophages (GAMs) remains largely unexplored. METHODS: To explore the pathophysiological relevance of oxylipin in human glioma, we performed Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) analysis in human glioma and non-tumor brain tissues. To comprehensively investigate the role of arachidonate lipoxygenase 5 (ALOX5) in glioma, we performed in vivo bioluminescent imaging, immunofluorescence staining and flow cytometry analysis on tumors from orthotopic glioma-bearing mice. We developed an ALOX5-targeted nanobody, and tested its anti-glioma efficacy of combination therapy with α-programmed cell death protein-1 (PD-1). RESULTS: In this study, we found that ALOX5 and its oxylipin 5-hydroxyeicosatetraenoic acid (5-HETE) are upregulated in glioma, accumulating programmed death-ligand 1 (PD-L1)+ M2-GAMs and orchestrating an immunosuppressive tumor microenvironment. Mechanistically, 5-HETE derived from ALOX5-overexpressing glioma cells, promotes GAMs migration, PD-L1 expression, and M2 polarization by facilitating nuclear translocation of nuclear factor erythroid 2-related factor 2. Additionally, a nanobody targeting ALOX5 is developed that markedly suppresses 5-HETE efflux from glioma cells, attenuates M2 polarization of GAMs, and consequently ameliorates glioma progression. Furthermore, the combination therapy of the ALOX5-targeted nanobody plus α-PD-1 exhibits superior anti-glioma efficacy. CONCLUSIONS: Our findings reveal a pivotal role of the ALOX5/5-HETE axis in regulating GAMs and highlight the ALOX5-targeted nanobody as a potential therapeutic agent, which could potentiate immune checkpoint therapy for glioma.

Advances in nucleic acid therapeutics: structures, delivery systems, and future perspectives in cancer treatment.

Cancer has emerged as a significant threat to human health. Nucleic acid therapeutics regulate the gene expression process by introducing exogenous nucleic acid fragments, offering new possibilities for tumor remission and even cure. Their mechanism of action and high specificity demonstrate great potential in cancer treatment. However, nucleic acid drugs face challenges such as low stability and limited ability to cross physiological barriers in vivo. To address these issues, various nucleic acid delivery vectors have been developed to enhance the stability and facilitate precise targeted delivery of nucleic acid drugs within the body. In this review article, we primarily introduce the structures and principles of nucleic acid drugs commonly used in cancer therapy, as well as their cellular uptake and intracellular transportation processes. We focus on the various vectors commonly employed in nucleic acid drug delivery, highlighting their research progress and applications in recent years. Furthermore, we propose potential trends and prospects of nucleic acid drugs and their carriers in the future.

Global diversity and ecological functions of viruses inhabiting oil reservoirs.

Oil reservoirs, being one of the significant subsurface repositories of energy and carbon, host diverse microbial communities affecting energy production and carbon emissions. Viruses play crucial roles in the ecology of microbiomes, however, their distribution and ecological significance in oil reservoirs remain undetermined. Here, we assemble a catalogue encompassing viral and prokaryotic genomes sourced from oil reservoirs. The catalogue comprises 7229 prokaryotic genomes and 3,886 viral Operational Taxonomic Units (vOTUs) from 182 oil reservoir metagenomes. The results show that viruses are widely distributed in oil reservoirs, and 85% vOTUs in oil reservoir are detected in less than 10% of the samples, highlighting the heterogeneous nature of viral communities within oil reservoirs. Through combined microcosm enrichment experiments and bioinformatics analysis, we validate the ecological roles of viruses in regulating the community structure of sulfate reducing microorganisms, primarily through a virulent lifestyle. Taken together, this study uncovers a rich diversity of viruses and their ecological functions within oil reservoirs, offering a comprehensive understanding of the role of viral communities in the biogeochemical cycles of the deep biosphere.

Deep-sea microorganisms-driven V5+ and Cd2+ removal from vanadium smelting wastewater: Bacterial screening, performance and mechanism.

The disorderly discharge of industrial wastewater containing heavy metals has caused serious water pollution and ecological environmental risks, ultimately threatening human life and health. Biological treatment methods have obvious advantages, but the existing microorganisms exhibit issues such as poor resistance, adaptability, colonization ability, and low activity. However, a wide variety of microorganisms in deep-sea hydrothermal vent areas are tolerant to heavy metals, possessing the potential for efficient treatment of heavy metal wastewater. Based on this, the study obtained a group of deep-sea microbial communities dominated by Burkholderia-Caballeronia-Paraburkholderia through shake flask experiments from the sediments of deep-sea hydrothermal vents, which can simultaneously achieve the synchronous removal of vanadium and cadmium heavy metals through bioreduction, biosorption, and biomineralization. Through SEM-EDS, XRD, XPS, and FT-IR analyses, it was found that V(V) was reduced to V(IV) through a reduction process and subsequently precipitated. Glucose oxidation accelerated this process. Cd(II) underwent biomineralization to form precipitates such as cadmium hydroxide and cadmium carbonate. Functional groups on the microbial cell surface, such as -CH2, C=O, N-H, -COOH, phosphate groups, amino groups, and M-O moieties, participated in the bioadsorption processes of V(V) and Cd(II) heavy metals. Under optimal conditions, namely a temperature of 40 °C, pH value of 7.5, inoculation amount of 10%, salinity of 4%, COD concentration of 600 mg/L, V5+ concentration of 300 mg/L, and Cd2+ concentration of 40 mg/L, the OD600 can reach its highest at 72 h, with the removal efficiency of V5+, Cd2+, and COD in simulated vanadium smelting wastewater reaching 86.32%, 59.13%, and 61.63%, respectively. This study provides theoretical insights and practical evidence for understanding the dynamic changes in microbial community structure under heavy metal stress, as well as the resistance mechanisms of microbial treatment of industrial heavy metal wastewater.

Species-level understanding of the bacterial community in Daqu based on full-length 16S rRNA gene sequences.

Daqu is used as the fermentation starter of Baijiu and contributes diversified functional microbes for saccharifying grains and converting sugars into ethanol and aroma components in Baijiu products. Daqu is mainly classified into three types, namely low (LTD), medium (MTD) and high (HTD) temperature Daqu, according to the highest temperatures reached in their fermentation processes. In this study, we used the PacBio small-molecule real-time (SMRT) sequencing technology to determine the full-length 16 S rRNA gene sequences from the metagenomes of 296 samples of different types of Daqu collected from ten provinces in China, and revealed the bacterial diversity at the species level in the Daqu samples. We totally identified 310 bacteria species, including 78 highly abundant species (with a relative abundance >0.1% each) which accounted for 91.90% of the reads from all the Daqu samples. We also recognized the differentially enriched bacterial species in different types of Daqu, and in the Daqu samples with the same type but from different provinces. Specifically, Lactobacillales, Enterobacterales and Bacillaceae were significantly enriched in the LTD, MTD and HTD groups, respectively. The potential co-existence and exclusion relationships among the bacteria species involved in all the Daqu samples and in the LTD, MTD and HTD samples from a specific region were also identified. These results provide a better understanding of the bacterial diversity in different types of Daqu at the species level.

Astragaloside IV protects renal tubular epithelial cells against oxidative stress-induced injury by upregulating CPT1A-mediated HSD17B10 lysine succinylation in diabetic kidney disease.

Tubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high-glucose-stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta-hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl-transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high-glucose-induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress-associated proximal tubular injury by upregulating CPT1A-mediated K99 succinylation of HSD17B10 to maintain RNase P activity.

MuCoCP: a priori chemical knowledge-based multimodal contrastive learning pre-trained neural network for the prediction of cyclic peptide membrane penetration ability.

MOTIVATION: There has been a burgeoning interest in cyclic peptide therapeutics due to their various outstanding advantages and strong potential for drug formation. However, it is undoubtedly costly and inefficient to use traditional wet lab methods to clarify their biological activities. Using artificial intelligence instead is a more energy-efficient and faster approach. MuCoCP aims to build a complete pre-trained model for extracting potential features of cyclic peptides, which can be fine-tuned to accurately predict cyclic peptide bioactivity on various downstream tasks. To maximize its effectiveness, we use a novel data augmentation method based on a priori chemical knowledge and multiple unsupervised training objective functions to greatly improve the information-grabbing ability of the model. RESULTS: To assay the efficacy of the model, we conducted validation on the membrane-permeability of cyclic peptides which achieved an accuracy of 0.87 and R-squared of 0.503 on CycPeptMPDB using semi-supervised training and obtained an accuracy of 0.84 and R-squared of 0.384 using a model with frozen parameters on an external dataset. This result has achieved state-of-the-art, which substantiates the stability and generalization capability of MuCoCP. It means that MuCoCP can fully explore the high-dimensional information of cyclic peptides and make accurate predictions on downstream bioactivity tasks, which will serve as a guide for the future de novo design of cyclic peptide drugs and promote the development of cyclic peptide drugs. AVAILABILITY AND IMPLEMENTATION: All code used in our proposed method can be found at https://github.com/lennonyu11234/MuCoCP.

An Apoptosis-Related Specific Risk Model for Breast Cancer: From Genomic Analysis to Precision Medicine.

BACKGROUND: Breast cancer (BC) ranks as the most prevalent malignancy affecting women globally, with apoptosis playing a pivotal role in its pathological progression. Despite the crucial role of apoptosis in BC development, there is limited research exploring the relationship between BC prognosis and apoptosis-related genes (ARGs). Therefore, this study aimed to establish a BC-specific risk model centered on apoptosis-related factors, presenting a novel approach for predicting prognosis and immune responses in BC patients. METHODS: Utilizing data from The Cancer Gene Atlas (TCGA), Cox regression analysis was employed to identify differentially prognostic ARGs and construct prognostic models. The accuracy and clinical relevance of the model, along with its efficacy in predicting immunotherapy outcomes, were evaluated using independent datasets, Receiver Operator Characteristic (ROC) curves, and nomogram. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were used to predict potential mechanical pathways. The CellMiner database is used to assess drug sensitivity of model genes. RESULTS: A survival risk model comprising eight prognostically relevant apoptotic genes (PMAIP1, TP53AIP1, TUBA3D, TUBA1C, BCL2A1, EMP1, GSN, F2) was established based on BC patient samples from TCGA. Calibration curves validated the ROC curve and nomogram, demonstrating excellent accuracy and clinical utility. In samples from the Gene Expression Omnibus (GEO) datasets and immunotherapy groups, the low-risk group (LRG) demonstrated enhanced immune cell infiltration and improved immunotherapy responses. Model genes also displayed positive associations with sensitivity to multiple drugs, including vemurafenib, dabrafenib, PD-98059, and palbociclib. CONCLUSIONS: This study successfully developed and validated a prognostic model based on ARGs, offering new insights into prognosis and immune response prediction in BC patients. These findings hold promise as valuable references for future research endeavors in this field.

Predictive value of an ultrasound-based radiomics model for central lymph node metastasis of papillary thyroid carcinoma.

Purpose: We aimed to explore the predictive value of an ultrasound-based radiomics model for the central lymph node metastasis of papillary thyroid carcinoma. Methods: A total of 126 patients with papillary thyroid carcinoma treated between February 2021 and February 2023 were retrospectively enrolled and assigned into metastasis group (n=59, with cervical central lymph node metastasis) or non-metastasis group (n=67, without metastasis) based on surgical and pathological findings. Intergroup comparisons were conducted on the results of contrast-enhanced ultrasonography, preoperative conventional ultrasonography, as well as real-time shear wave elastography. Results: The maximum lesion diameter, echo, margin, capsule invasion, calcification, average elasticity modulus (Eavg), rising time (RT), and peak intensity (PI) had diagnostic value for papillary thyroid carcinoma, and their combination exhibited higher diagnostic value (area under the curve: 0.817). The logistic regression model was built, and the maximum lesion diameter, hypoechoic/extremely hypoechoic, lobulated or irregular margin (95% confidence interval: 1.451-6.755), capsule invasion, microcalcification/macrocalcification or peripheral calcification, high-level Eavg, low-level RT and high-level PI served as risk elements affecting papillary thyroid carcinoma from the aspect of central lymph node metastasis (odds ratio>1, P<0.05). According to the logistic regression model, the model was reliable and stable (area under the curve: 0.889, P<0.05). Conclusion: The established ultrasound-based radiomics model can be utilized for early identifying the central lymph node metastasis of papillary thyroid carcinoma.

Global Highly Cited Publication Trends and Research Hotspots in Osteoporosis and Bone Metabolic Cells: A Bibliometric and Visualization Analysis from 2013 to 2023.

BACKGROUND: Bone metabolic diseases such as osteoporosis are caused by disruption of the metabolic balance between osteoblasts and osteoclasts. Thousands of papers have been published on osteoporosis and bone metabolizing cells. The purpose of this study is to draw the publication trend of highly cited literature in this field through bibliometrics and to explore the research hotspot analysis. OBJECTIVE: This paper provides a comprehensive analysis of the impact of countries/regions, research institutions, authors, keywords, relevant journals, and references in the field of osteoporosis and bone metabolic cells research, with a specific focus on the theme of "Osteoporosis and bone metabolic cells". Furthermore, utilizing bibliometric methods, the study aims to offer valuable insights and references for future research endeavors, as well as clinical prevention and treatment strategies in this domain. METHODS: The Web of Science [WOS] Core Collection database was examined in order to identify articles with high citation counts from 2013 to 31 October 2023. The citation counts, authors, year of publication, source, journal, geographical origin, subject, article type, and level of evidence were further analyzed using the R bibliometric package. The VOSviewer software was utilized to visualize word co-occurrence in a total of 251 articles. RESULTS: Our search strategy included 251 highly cited articles published between 2013 and 2023 in the field of osteoporosis and bone metabolic cells. The number of publications in this field remains consistently high, indicating ongoing research interest. Notably, the United States has made significant achievements and contributions in this area. Xie Hui, Cao Xu, and Goodman, Stewart are among the main contributors to these advancements. NATURE MEDICINE has the highest journal impact factor of 82.9, highlighting its prominence. The JOURNAL OF BONE AND MINERAL RESEARCH ranks first with 1,322 citations. Keyword research topics in this field include osteoclast differentiation, osteoblast differentiation, and mesenchymal stem cells. Through citation analysis, we found that 195 articles have been cited more than 100 times, demonstrating their significance and impact. CONCLUSION: This study analyzed the relationship between osteoporosis and bone metabolic cells using a bibliometric method. The results of these analyses can help researchers gain a more direct and scientific understanding of trends in the field. Additionally, it can provide guidance in identifying hot research directions and offer new ideas for the prevention and treatment of osteoporosis.

Research Advances of Lipid Nanoparticles in the Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is a common type of gastrointestinal tract (GIT) cancer and poses an enormous threat to human health. Current strategies for metastatic colorectal cancer (mCRC) therapy primarily focus on chemotherapy, targeted therapy, immunotherapy, and radiotherapy; however, their adverse reactions and drug resistance limit their clinical application. Advances in nanotechnology have rendered lipid nanoparticles (LNPs) a promising nanomaterial-based drug delivery system for CRC therapy. LNPs can adapt to the biological characteristics of CRC by modifying their formulation, enabling the selective delivery of drugs to cancer tissues. They overcome the limitations of traditional therapies, such as poor water solubility, nonspecific biodistribution, and limited bioavailability. Herein, we review the composition and targeting strategies of LNPs for CRC therapy. Subsequently, the applications of these nanoparticles in CRC treatment including drug delivery, thermal therapy, and nucleic acid-based gene therapy are summarized with examples provided. The last section provides a glimpse into the advantages, current limitations, and prospects of LNPs in the treatment of CRC.