Optomechanical Frequency Comb Based on Multiple Nonlinear Dynamics.

Phonon-based frequency combs that can be generated in the optical and microwave frequency domains have attracted much attention due to the small repetition rates and the simple setup. Here, we experimentally demonstrate a new type of phonon-based frequency comb in a silicon optomechanical crystal cavity including both a breathing mechanical mode (∼GHz) and flexural mechanical modes (tens of MHz). We observe strong mode competition between two approximate flexural mechanical modes, i.e., 77.19 and 90.17 MHz, resulting in only one preponderant lasing, while maintaining the lasing of the breathing mechanical mode. These simultaneous observations of two-mode phonon lasing state and significant mode competition are counterintuitive. We have formulated comprehensive theories to elucidate this phenomenon in response to this intriguing outcome. In particular, the self-pulse induced by the free carrier dispersion and thermo-optic effects interacts with two approximate flexural mechanical modes, resulting in the repetition rate of the comb frequency-locked to exact fractions of one of the flexural mechanical modes and the mode hopping between them. This phonon-based frequency comb has at least 260 comblines and a repetition rate as low as a simple fraction of the flexural mechanical frequency. Our demonstration offers an alternative optomechanical frequency comb for sensing, timing, and metrology applications.

Metal-Organic Framework-Based Nanovaccine for Relieving Immunosuppressive Tumors via Hindering Efferocytosis of Macrophages and Promoting Pyroptosis and Cuproptosis of Cancer Cells.

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability to produce an effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) and XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal-organic framework to in situ-generate therapeutic vaccination. Once inside the early endosome, the alkaline phosphatase overexpressed in the tumor cells' membrane activates the in situ type I photodynamic effect of Cu-THBQ/AX for generating •O2-, and the Cu-THBQ/AX catalyzes O2 and H2O2 to •O2- and •OH via semiquinone radical catalysis and Fenton-like reactions. This surge of ROS in early endosomes triggers caspase-3-mediated proinflammatory pyroptosis via activating phospholipase C. Meanwhile, Cu-THBQ/AX can also induce the oligomerization of dihydrolipoamide S-acetyltransferase to trigger tumor cell cuproptosis. The production of •OH could also trigger the release of XMD8-92 for effectively inhibiting the efferocytosis of macrophages to convert immunosuppressive apoptosis of cancer cells into proinflammatory secondary necrosis. The simultaneous induction of pyroptosis, cuproptosis, and secondary necrosis effectively converts the tumor microenvironment from "cold" to "hot" conditions, making it an effective antigen pool. This transformation successfully activates the antitumor immune response, inhibiting tumor growth and metastasis.

Defect-rich sonosensitizers based on CeO2 with Schottky heterojunctions for boosting sonodynamic/chemodynamic synergistic therapy.

Sonodynamic therapy (SDT) has been recognized as a promising treatment for cancer due to its advantages of superior specificity, non-invasiveness, and deep tissue penetration. However, the antitumor effect of SDT remains restricted by the limited generation of reactive oxygen species (ROS) due to the lack of highly efficient sonosensitizers. In this work, we developed the novel sonosensitizer Pt/CeO2-xSx by constructing oxygen defects through S doping and Pt loading in situ. Large amounts of oxygen defects have been obtained by S doping, endowing Pt/CeO2-xSx with the ability to suppress electron-hole recombination, further promoting ROS production. Moreover, the introduction of Pt nanoparticles can not only produce oxygen in situ for relieving hypoxia but also form a Schottky heterojunction with CeO2-xSx for further inhibiting electron-hole recombination. In addition, Pt/CeO2-xSx could effectively deplete overexpressed glutathione (GSH) via redox reactions, amplifying oxidative stress in the tumor microenvironment (TME). Combined with the excellent POD-mimetic activity, Pt/CeO2-xSx can achieve highly efficient synergistic therapy of SDT and chemodynamic therapy (CDT). All these findings demonstrated that Pt/CeO2-xSx has great potential for cancer therapy, and this work provides a promising direction for designing and constructing efficient sonosensitizers.

GLIMS: A two-stage gradual-learning method for cancer genes prediction using multi-omics data and co-splicing network.

Identifying cancer genes is vital for cancer diagnosis and treatment. However, because of the complexity of cancer occurrence and limited cancer genes knowledge, it is hard to identify cancer genes accurately using only a few omics data, and the overall performance of existing methods is being called for further improvement. Here, we introduce a two-stage gradual-learning strategy GLIMS to predict cancer genes using integrative features from multi-omics data. Firstly, it uses a semi-supervised hierarchical graph neural network to predict the initial candidate cancer genes by integrating multi-omics data and protein-protein interaction (PPI) network. Then, it uses an unsupervised approach to further optimize the initial prediction by integrating the co-splicing network in post-transcriptional regulation, which plays an important role in cancer development. Systematic experiments on multi-omics cancer data demonstrated that GLIMS outperforms the state-of-the-art methods for the identification of cancer genes and it could be a useful tool to help advance cancer analysis.

Multisource working condition recognition via nonlinear kernel learning and p-Laplacian manifold learning.

Effectively utilizing information from multiple sources and fewer labeled operating condition samples from a sucker-rod pumping system for oil production can improve the recognition effects and engineering practicability. Nevertheless, this is a challenging energy environment scientific application research subject, and therefore, this study proposes an operating state recognition scheme that relies on multisource nonlinear kernel learning and p-Laplacian high-order manifold regularization logistic regress. Specifically, three measured features are selected and extracted, i.e., wellhead temperature signal, electrical power signal, and ground dynamometer cards, based on mechanism analysis, expert experience, and prior knowledge. Finally, we establish the operating condition recognition model to recognize by the multisource p-Laplacian regularization kernel logistic regress algorithm. The experimental data are derived from 60 wells of a common high-pressure and low-permeability thin oil reservoir block of an oil field in China. The corresponding trials highlight that our scheme outperforms traditional recognition methods by exploiting single-source and multiple-feature data. In the context of fewer labeled samples, the proposed method has a greater recognition effect, engineering practicability, and better model robustness than the existing schemes based on other high-order manifold learning, verifying our method's effectiveness.

Chronic exposure to PM10 induces anxiety-like behavior via exacerbating hippocampal oxidative stress.

As one of the most environmental concerns, inhaled particulate matter (PM10) causes numerous health problems. However, the associations between anxiety behavior and toxicity caused by PM10 have rarely been reported so far. To investigate the changes of behavior after PM10 exposure and to identify the potential mechanisms of toxicity, PM10 samples (with doses of 15 mg/kg and 30 mg/kg) were intratracheally instilled into rats to simulate inhalation of polluted air by the lungs. After instillation for eight weeks, anxiety-like behavior was evaluated, levels of oxidative stress and morphological changes of hippocampus were measured. The behavioral results indicated that PM10 exposure induced obvious anxiety-like behavior in the open field and elevated plus maze tests. Both PM10 concentrations tested could increase whole blood viscosity and trigger hippocampal neuronal damage and oxidative stress by increasing superoxide dismutase (SOD) activities and malondialdehyde levels, and decreasing the expressions of antioxidant-related proteins (e.g., nuclear factor erythroid 2-related factor 2 (Nrf2), SOD1 and heme oxygenase 1). Furthermore, through collecting and analyzing questionnaires, the data showed that the participants experienced obvious anxiety-related emotions and negative somatic responses under heavily polluted environments, especially PM10 being the main pollutant. These results show that PM10 exposure induces anxiety-like behavior, which may be related to suppressing the Nrf2/Keap1-SOD1 pathway.

Predictive potentials of glycosylation-related genes in glioma prognosis and their correlation with immune infiltration.

Glycosylation is currently considered to be an important hallmark of cancer. However, the characterization of glycosylation-related gene sets has not been comprehensively analyzed in glioma, and the relationship between glycosylation-related genes and glioma prognosis has not been elucidated. Here, we firstly found that the glycosylation-related differentially expressed genes in glioma patients were engaged in biological functions related to glioma progression revealed by enrichment analysis. Then seven glycosylation genes (BGN, C1GALT1C1L, GALNT13, SDC1, SERPINA1, SPTBN5 and TUBA1C) associated with glioma prognosis were screened out by consensus clustering, principal component analysis, Lasso regression, and univariate and multivariate Cox regression analysis using the TCGA-GTEx database. A glycosylation-related prognostic signature was developed and validated using CGGA database data with significantly accurate prediction on glioma prognosis, which showed better capacity to predict the prognosis of glioma patients than clinicopathological factors do. GSEA enrichment analysis based on the risk score further revealed that patients in the high-risk group were involved in immune-related pathways such as cytokine signaling, inflammatory responses, and immune regulation, as well as glycan synthesis and metabolic function. Immuno-correlation analysis revealed that a variety of immune cell infiltrations, such as Macrophage, activated dendritic cell, Regulatory T cell (Treg), and Natural killer cell, were increased in the high-risk group. Moreover, functional experiments were performed to evaluate the roles of risk genes in the cell viability and cell number of glioma U87 and U251 cells, which demonstrated that silencing BGN, SDC1, SERPINA1, TUBA1C, C1GALT1C1L and SPTBN5 could inhibit the growth and viability of glioma cells. These findings strengthened the prognostic potentials of our predictive signature in glioma. In conclusion, this prognostic model composed of 7 glycosylation-related genes distinguishes well the high-risk glioma patients, which might potentially serve as caner biomarkers for disease diagnosis and treatment.

Single-Site Nanozymes with a Highly Conjugated Coordination Structure for Antitumor Immunotherapy via Cuproptosis and Cascade-Enhanced T Lymphocyte Activity.

The extracellular matrix (ECM) in the tumor microenvironment (TME) and upregulated immune checkpoints (ICs) on antitumor immune cells impede the infiltration and killing effect of T cells, creating an immunosuppressive TME. Herein, a cholesterol oxidase (CHO) and lysyl oxidase inhibitor (LOX-IN-3) co-delivery copper-dibenzo-[g,p]chrysene-2,3,6,7,10,11,14,15-octaol single-site nanozyme (Cu-DBCO/CL) was developed. The conjugated organic ligand and well-distributed Cu-O4 sites endow Cu-DBCO with unique redox capabilities, enabling it to catalyze O2 and H2O2 to ·O2- and ·OH. This surge of reactive oxygen species (ROS) leads to impaired mitochondrial function and insufficient ATP supply, impacting the function of copper-transporting ATPase-1 and causing dihydrolipoamide S-acetyltransferase oligomerization-mediated cuproptosis. Moreover, multiple ROS storms and glutathione peroxidase 4 depletion also induce lipid peroxidation and trigger ferroptosis. Simultaneously, the ROS-triggered release of LOX-IN-3 reshapes the ECM by inhibiting lysyl oxidase activity and further enhances the infiltration of cytotoxic T lymphocytes (CD8+ T cells). CHO-triggered cholesterol depletion not only increases ·OH generation but also downregulates the expression of ICs such as PD-1 and TIM-3, restoring the antitumor activity of tumor-infiltrating CD8+ T cells. Therefore, Cu-DBCO/CL exhibits efficient properties in activating a potent antitumor immune response by cascade-enhanced CD8+ T cell viability. More importantly, ECM remodeling and cholesterol depletion could suppress the metastasis and proliferation of the tumor cells. In short, this immune nanoremodeler can greatly enhance the infiltration and antitumor activity of T cells by enhancing tumor immunogenicity, remodeling ECM, and downregulating ICs, thus achieving effective inhibition of tumor growth and metastasis.

Contrast-enhanced ultrasound to predict malignant upgrading of atypical ductal hyperplasia.

BACKGROUND: A malignancy might be found at surgery in cases of atypical ductal hyperplasia (ADH) diagnosed via US-guided core needle biopsy (CNB). The objective of this study was to investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in predicting ADH diagnosed by US-guided CNB that was upgraded to malignancy after surgery. METHODS: In this retrospective study, 110 CNB-diagnosed ADH lesions in 109 consecutive women who underwent US, CEUS, and surgery between June 2018 and June 2023 were included. CEUS was incorporated into US BI-RADS and yielded a CEUS-adjusted BI-RADS. The diagnostic performance of US BI-RADS and CEUS-adjusted BI-RADS for ADH were analyzed and compared. RESULTS: The mean age of the 109 women was 49.7 years ± 11.6 (SD). The upgrade rate of ADH at CNB was 48.2% (53 of 110). The sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for identification of malignant upgrading were 96.2%, 66.7%,72.9%, and 95.0%, respectively, based on BI-RADS category 4B threshold. The two false-negative cases were low-grade ductal carcinoma in situ. Compared with the US, CEUS-adjusted BI-RADS had better specificity for lesions smaller than 2 cm (76.7% vs. 96.7%, P = 0.031). After CEUS, 16 (10 malignant and 6 nonmalignant) of the 45 original US BI-RADS category 4A lesions were up-classified to BI-RADS 4B, and 3 (1 malignant and 2 nonmalignant) of the 41 original US BI-RADS category 4B lesions were down-classified to BI-RADS 4A. CONCLUSIONS: CEUS is helpful in predicting malignant upgrading of ADH, especially for lesions smaller than 2 cm and those classified as BI-RADS 4A and 4B on ultrasound.

Programmed Targeting Pyruvate Metabolism Therapy Amplified Single-Atom Nanozyme-Activated Pyroptosis for Immunotherapy.

Increasing cellular immunogenicity and reshaping the immune tumor microenvironment (TME) are crucial for antitumor immunotherapy. Herein, this work develops a novel single-atom nanozyme pyroptosis initiator: UK5099 and pyruvate oxidase (POx)-co-loaded Cu-NS single-atom nanozyme (Cu-NS@UK@POx), that not only trigger pyroptosis through cascade biocatalysis to boost the immunogenicity of tumor cells, but also remodel the immunosuppressive TME by targeting pyruvate metabolism. By replacing N with weakly electronegative S, the original spatial symmetry of the Cu-N4 electron distribution is changed and the enzyme-catalyzed process is effectively regulated. Compared to spatially symmetric Cu-N4 single-atom nanozymes (Cu-N4 SA), the S-doped spatially asymmetric single-atom nanozymes (Cu-NS SA) exhibit stronger oxidase activities, including peroxidase (POD), nicotinamide adenine dinucleotide (NADH) oxidase (NOx), L-cysteine oxidase (LCO), and glutathione oxidase (GSHOx), which can cause enough reactive oxygen species (ROS) storms to trigger pyroptosis. Moreover, the synergistic effect of Cu-NS SA, UK5099, and POx can target pyruvate metabolism, which not only improves the immune TME but also increases the degree of pyroptosis. This study provides a two-pronged treatment strategy that can significantly activate antitumor immunotherapy effects via ROS storms, NADH/glutathione/L-cysteine consumption, pyruvate oxidation, and lactic acid (LA)/ATP depletion, triggering pyroptosis and regulating metabolism. This work provides a broad vision for expanding antitumor immunotherapy.

Obstructive sleep apnea (OSA) is associated with increased risk of early-onset sarcopenia and sarcopenic obesity: Results from NHANES 2015-2018.

OBJECTIVE: This study aims to estimate the prevalence of early-onset sarcopenia and sarcopenic obesity in the United States and its relative risk due to obstructive sleep apnea (OSA). METHODS: Data in this cross-sectional study were extracted from the National Health and Nutritional Examination Survey (NHANES) 2015-2018. Weighted multistage stratified probability sampling design was considered to estimate the prevalence of early-onset sarcopenia and sarcopenic obesity. Weighted multivariable logistic regression analyses and weighted multivariable mediation models were performed to evaluate the association between OSA and early-onset sarcopenia. RESULTS: The prevalence of early-onset sarcopenia and early-onset sarcopenic obesity was estimated to be 5.5% and 4.6%, respectively. A higher prevalence of sarcopenia (12% V.S. 5.5%, P < 0.01) and sarcopenic obesity (10.3% V.S. 4.0%, P < 0.01) was observed among participants with OSA than those without OSA. Multivariable logistic regression models suggested that participants with OSA had higher odds ratios of suffering from early-onset sarcopenia [Odds Ratio (OR): 1.5, 95% confidence interval (CI):1.1-2.7] and early-onset sarcopenic obesity [OR: 1.8, 95% CI: 1.1-3.1] after adjusting for potential confounding variables. Mediation analyses suggested serum chronic reaction protein (CRP) mediated 23.7% (P < 0.01) & 26.2% (P < 0.01), homeostasis model assessment insulin resistance index (HOMA-IR) mediated 24.8% (P < 0.01) & 20.7% (P < 0.05), body mass index (BMI) mediated 46.4% (P < 0.05) & 49.9% (P < 0.01), HEI-2015 mediated 23.3% (P < 0.01) & 25.6% (P < 0.01), and Vitamin D mediated 7.5% (P < 0.01) & 8.5% (P < 0.01) of the potential effects of OSA on early-onset sarcopenia and sarcopenic obesity, respectively. CONCLUSION: Early-onset sarcopenia and sarcopenic obesity were prevalent among young adults in the US. OSA is a significant independent risk factor and may induce muscle loss by unhealthy diet habits, higher BMI, chronic inflammation, insulin resistance, and Vitamin D. It was essential for clinicians to arrange appropriate screening and interventions for patients with OSA to prevent muscle loss as early as possible.

Repetition rate tuning and locking of solitons in a microrod resonator.

Recently, there has been significant interest in the generation of coherent temporal solitons in optical microresonators. In this Letter, we present a demonstration of dissipative Kerr soliton generation in a microrod resonator using an auxiliary-laser-assisted thermal response control method. In addition, we are able to control the repetition rate of the soliton over a range of 200 kHz while maintaining the pump laser frequency, by applying external stress tuning. Through the precise control of the PZT voltage, we achieve a stability level of 3.9 × 10-10 for residual fluctuation of the repetition rate when averaged 1 s. Our platform offers precise tuning and locking capabilities for the repetition frequency of coherent mode-locked combs in microresonators. This advancement holds great potential for applications in spectroscopy and precision measurements.

Predicting circRNA-miRNA interactions utilizing transformer-based RNA sequential learning and high-order proximity preserved embedding.

A key regulatory mechanism involves circular RNA (circRNA) acting as a sponge to modulate microRNA (miRNA), and thus, studying their interaction has significant medical implications. In this field, there are currently two pressing issues that remain unresolved. Firstly, due to the scarcity of verified interactions, we require a minimal amount of samples for training. Secondly, the current models lack interpretability. Therefore, we propose SPBCMI, a method that combines sequence features extracted using the Bidirectional Encoder Representations from Transformer (BERT) model and structural features of biological molecule networks extracted through graph embedding to train a GBDT (Gradient-boosted decision trees) classifier for prediction. Our method yielded an AUC of 0.9143, which is currently the best for this problem. Furthermore, in the case study, SPBCMI accurately predicted 7 out of 10 circRNA-miRNA interactions. These results show that our method provides an innovative and high-performing approach to understanding the interaction between circRNA and miRNA.

Study of clinical traits and systemic immune inflammation index assessments in patients with endogenous endophthalmitis over the last ten years.

PURPOSE: The clinical aspects and prognosis of eyes with endogenous endophthalmitis were compared over the last ten years. The occurrence and progression of endophthalmitis are linked to the systemic immune inflammation index (SII) and clinical features. METHODS: The study comprised patients with endogenous endophthalmitis and 64 patients without endophthalmitis who were treated at Hebei Province Eye Hospital in the last ten years. According to the prognostic visual acuity, patients with endophthalmitis were split into two groups: Group A and Group B. Underlying disease (hypertension, diabetes, tuberculosis), infection risk (liver abscess, urinary tract infection, and recent abdominal surgery), signs and symptoms, and complete blood count were among the evaluation parameters (neutrophil count, lymphocyte count, monocyte count, platelet count, red blood cell distribution width). The NLR, PLR, MLR, and SII values were calculated. A nonparametric test was used to examine the clinical features and complete blood count results of patients in each group. To determine the parameters linked to endophthalmitis progression, researchers used principal component and ordinal logistic regression analyses. RESULTS: The study comprised a total of 25 eyes and 22 individuals with endogenous endophthalmitis. Infectious bacteria included Staphylococcus aureus, Micrococcus luteus, Staphylococcus hemolyticus, and so on. The visual acuity of the affected eye ranged from 2.7 (1.55, 2.7) LogMAR to 1.22 (0.6, 2.7) LogMAR during the 6-month to 8-year follow-up period. The neutrophil, monocyte, and PLT counts, NLR, PLR, and SII values and other markers were considerably higher in Groups A and B than in the control group. The likelihood model of the SII and sex, age, onset time, diabetes, hypertension, monocyte count, and red blood cell distribution was the best, and its increase was strongly connected with the occurrence and progression of endophthalmitis, according to ordinal regression analysis. CONCLUSION: Patients with endophthalmitis had significantly higher blood neutrophil, monocyte, and PLT counts and SII, NLR, PLR, and MLR values. The SII can be employed as a biomarker for predicting endophthalmitis severity and prognosis.

Enhanced Superconductivity and Critical Current Density Due to the Interaction of InSe2 Bonded Layer in (InSe2)0.12NbSe2.

Superconductivity was discovered in (InSe2)xNbSe2. The materials are crystallized in a unique layered structure where bonded InSe2 layers are intercalated into the van der Waals gaps of 2H-phase NbSe2. The (InSe2)0.12NbSe2 superconductor exhibits a superconducting transition at 11.6 K and critical current density of 8.2 × 105 A/cm2. Both values are the highest among all transition metal dichalcogenide superconductors at ambient pressure. The present finding provides an ideal material platform for further investigation of superconducting-related phenomena in transition metal dichalcogenides.

Giant optical absorption of a PtSe2-on-silicon waveguide in mid-infrared wavelengths.

Low-dimensional platinum diselenide (PtSe2) is a promising candidate for high-performance optoelectronics in the short-wavelength mid-infrared band due to its high carrier mobility, excellent stability, and tunable bandgap. However, light usually interacts moderately with low-dimensional PtSe2, limiting the optoelectronic responses of PtSe2-based devices. Here we demonstrated a giant optical absorption of a PtSe2-on-silicon waveguide by integrating a ten-layer PtSe2 film on an ultra-thin silicon waveguide. The weak mode confinement in the ultra-thin waveguide dramatically increases the waveguide mode overlap with the PtSe2 film. Our experimental results show that the absorption coefficient of the PtSe2-on-silicon waveguide is in the range of 0.0648 dB µm-1 to 0.0704 dB µm-1 in a spectral region of 2200 nm to 2300 nm wavelengths. Furthermore, we also studied the optical absorption in an ultra-thin silicon microring resonator. Our study provides a promising approach to developing PtSe2-on-silicon hybrid optoelectronic integrated circuits.

Comparisons of clinical outcomes between newly diagnosed early- and late-onset T2DM: a real-world study from the Shanghai Hospital Link Database.

Objective: The aim of this study was to compare the differences in incident population, comorbidities, and glucose-lowering drug prescriptions between newly diagnosed patients with early-onset type 2 diabetes mellitus (T2DM) and those with late-onset T2DM to provide real-world evidence for clinical practice. Methods: This study was based on the Shanghai Hospital Link Database (SHLD). Anonymized electronic medical record (EHR) data from 2013 to 2021 were included in this study. Newly diagnosed patients with T2DM were defined as those without related diagnostic records or glucose-lowering medicine prescriptions in the past 3 years. Early-onset T2DM was defined as patients who were aged 18-40 years old at the first visit for T2DM to represent those who were born after the 1980s. And late-onset T2DM was defined as those aged 65-80 years old to represent those who were born in a relatively undeveloped period. Descriptive statistical analyses were performed to describe their incidence number, glucose-lowering drug prescriptions, and comorbidities at the first visit to the hospital between two T2DM groups. Results: There were a total of 35,457 newly diagnosed patients with early-onset T2DM and 149,108 newly diagnosed patients with late-onset T2DM included in this study. Patients with late-onset T2DM constituted the majority and their number increased by 2.5% on average by years, while the number of patients with early-onset T2DM remained stable each year. Compared with late-onset T2DM patients, more early-onset T2DM patients had dyslipidemia at the first visit to hospitals (9.5% vs 7.7%, P < 0.01) despite their significant age differences. Patients with early-onset T2DM were more likely to use metformin (74.8% vs 46.5, P < 0.01), dipeptidyl peptidase-4 inhibitors (DDP-4i) (16.7% vs 11.2%, P < 0.01), thiazolidinediones (TZD) (14.9% vs 8.4%, P < 0.01), sodium glucose cotransporter 2 inhibitors (SGLT2-i) (0.8% vs 0.3%, P < 0.01), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) (3.7% vs 0.5%, P < 0.01) at their first visit to the hospital. Conclusions: Different characteristics were observed between patients with early-onset T2DM and those with late-onset T2DM. Compared with patients with late-onset T2DM, those with early-onset T2DM were more prone to dyslipidemia and had novel organ-protective drugs prescribed.

Multi-Enzyme Co-Expressed Nanomedicine for Anti-Metastasis Tumor Therapy by Up-Regulating Cellular Oxidative Stress and Depleting Cholesterol.

Tumor cells movement and migration are inseparable from the integrity of lipid rafts and the formation of lamellipodia, and lipid rafts are also a prerequisite for the formation of lamellipodia. Therefore, destroying the lipid rafts is an effective strategy to inhibit tumor metastasis. Herein, a multi-enzyme co-expressed nanomedicine: cholesterol oxidase (CHO) loaded Co─PN3 single-atom nanozyme (Co─PN3 SA/CHO) that can up-regulate cellular oxidative stress, disrupt the integrity of lipid rafts, and inhibit lamellipodia formation to induce anti-metastasis tumor therapy, is developed. In this process, Co─PN3 SA can catalyze oxygen (O2 ) and hydrogen peroxide (H2 O2 ) to generate reactive oxygen species (ROS) via oxidase-like and Fenton-like properties. The doping of P atoms optimizes the adsorption process of the intermediate at the active site and enhances the ROS generation properties of nanomedicine. Meantime, O2 produced by catalase-like catalysis can combine with excess cholesterol to generate more H2 O2 under CHO catalysis, achieving enhanced oxidative damage to tumor cells. Most importantly, cholesterol depletion in tumor cells also disrupts the integrity of lipid rafts and inhibits the formation of lamellipodia, greatly inhibiting the proliferation and metastasis of tumor cells. This strategy by up-regulating cellular oxidative stress and depleting cellular cholesterol constructs a new idea for anti-metastasis-oriented cancer therapy strategies.

Combination of Breast Ultrasound With Magnetic Resonance Imaging in the Diagnosis of Non-mass-like Breast Lesions Detected on Ultrasound: A New Integrated Strategy to Improve Diagnostic Performance.

OBJECTIVE: The aim of the work described here was to evaluate the diagnostic performance of a new integrated strategy using breast ultrasound (US) combined with magnetic resonance imaging (MRI) to differentiate benign and malignant breast non-mass-like lesions (NMLs) detected on US. METHODS: From October 2017 to January 2021, 183 NMLs detected on US that had undergone MRI examinations were included in this respective study. Pathological results were used as the reference standard. The integrated diagnostic strategy of breast US combined with MRI based on a combination of MRI Breast Imaging Reporting and Data System (BI-RADS) with discriminant sonographic indicators highly associated with malignancy was established and validated in a cohort of 61 women. The diagnostic performances of US, MRI and the combined method were calculated and compared. RESULTS: In the training set, the area under the receiver operating characteristic curve (AUC), sensitivity and specificity of US, MRI and the integrated diagnostic strategy using US combined with MRI for NMLs were 0.730, 93.7% and 52.3%; 0.849, 94.7% and 75.0%; and 0.901, 92.6% and 87.5%, respectively. Compared with US or MRI alone, the integrated diagnostic strategy significantly increased the AUC (p < 0.001, p = 0.007) and specificity (p < 0.001, p = 0.034) while maintaining high sensitivity (p = 0.774, p = 0.551). In the validation set, the integrated strategy of US combined with MRI (AUC = 0.899) also had good performance compared with US (AUC = 0.728) or MRI (AUC = 0.838). CONCLUSION: The integrated diagnostic strategy of US combined with MRI exhibited good performance for breast NMLs compared with either modality used alone, which can improve the diagnostic specificity while maintaining high sensitivity.