Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response.

Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor. Here we show that the epigenetic regulator ubiquitin-like with PHD and ring finger domains 1 (UHRF1), exhibits altered expression and aberrant cytosolic localization in cancerous tissues, where it promotes MHC-I ubiquitination and degradation. Cytoplasmic translocation of UHRF1 is induced by its phosphorylation on a specific serine in response to signals provided by factors present in the tumor microenvironment (TME), such as TGF-ß, enabling UHRF1 to bind MHC-I. Downregulation of MHC-I results in suppression of the antigen presentation pathway to establish an immune hostile TME. UHRF1 inactivation by genetic deletion synergizes with immune checkpoint blockade (ICB) treatment and induces an anti-tumour memory response by evoking low-affinity T cells. Our study adds to the understanding of UHRF1 in cancer immune evasion and provides a potential target to synergize with immunotherapy and overcome immunotherapeutic resistance.

HLTF/SERPINE1 Axis Plays a Crucial Pro-Oncogenic Role in the Progression from Cervical Precancerous Lesions to Cervical Carcinoma in vitro.

OBJECTIVES: Cervical carcinoma (CC) is prevalent among women worldwide with increasing risk. Finding effective methods for treating CC is of utmost importance. The aim of this study was to investigate the effect of SERPINE1 on the progression of cervical precancerous lesions to CC. DESIGN: This study used transcriptome sequencing and in vitro cell line. Participants/Materials: Cervical precancerous lesions and CC samples and human cervical epithelial immortalized cell line H8, human CC cell lines HeLa, and CaSki were involved in this study. SETTING AND METHODS: Next-generation sequencing was applied to identify 100 differentially expressed genes from cervical precancerous lesions and CC samples. With the application of the Search Tool for the Retrieval of Interacting Genes (STRING) database, we carried out the protein-protein interaction network analysis, thus screening out serine protease inhibitor clade E member 1 (SERPINE1) with significant upregulation in CC cells. The helicase-like transcription factor (HLTF) was predicted as the upstream transcription factor using Human Transcription Factor Database (HumanTFDB). The chromatin immunoprecipitation (ChIP) experiment was conducted to validate the interaction between SERPINE1 and HLTF. The immunohistochemistry was employed to determine the expression of SERPINE1 and HLTF in CC tissues. Following the upregulation or downregulation of SERPINE1 and HLTF, the real-time quantitative reverse transcription polymerase chain reaction was carried out to assess mRNA expression levels of SERPINE1 and HLTF in cells. Cell viability, migration, and invasion were evaluated using MTT assay, cell scratch assay, and Transwell assay, respectively. Western blot analysis was conducted to assess changes in the expression levels of matrix metalloproteinases and proteins related to epithelial-mesenchymal transition (EMT). RESULTS: The ChIP experiment confirmed the interaction between HLTF and SERPINE1. HLTF and SERPINE1 were upregulated in CC tissues and cells, and silencing SERPINE1 inhibited the EMT process and viability, migration, and invasion of CC cells. However, overexpression of SERPINE1 in CC cells showed the opposite trend. Rescue experiments demonstrated that silencing HLTF repressed CC cell viability, migration, and invasion, which could be restored by overexpressing SERPINE1. LIMITATIONS: The effect of the HLTF/SERPINE1 axis on CC malignant progression has not been confirmed by in vivo experiments. CONCLUSION: HLTF transcriptionally activates SERPINE1, promoting the progression from cervical precancerous lesions to CC.

Tunable Valley Pseudospin and Electron-Phonon Coupling in WSe2/1T-VSe2 Heterostructures.

Heterostructure engineering provides versatile platforms for exploring exotic physics and enhancing the device performance through interface coupling. Despite the rich array of physical phenomena presented by heterostructures composed of semiconductor and metal van der Waals materials, significant gaps remain in understanding their optical, thermal, and electronic properties. Here, we demonstrate that the valley pseudospin and electron-phonon coupling in monolayer WSe2 are significantly influenced by interface coupling with 1T-VSe2. The heterointerface alters the relaxation process of valley excitons, leading to a transition in magnetic-field-dependent valley polarization from a linear to a "V" shape. Furthermore, we uncover that enhanced electron-phonon coupling exacerbates variations in exciton and valley exciton behavior with temperature, involving higher phonon energies and a shift from acoustic to optical phonons. These findings highlight a promising pathway to manipulate valley excitons and investigate electron-phonon coupling through van der Waals interface interactions.

Giant Optical Anisotropy Induced by Magnetic Order in FePS3/WSe2 Heterostructures.

Magnetic 2D materials offer a promising platform for manipulating quantum states at the nanoscale. Recent studies have underscored the significant influence of 2D magnetic materials on the optical behaviors of transition-metal dichalcogenides (TMDs), revealing phenomena such as interlayer exciton-magnon interactions, magnetization-dependent valley polarization, and an enhanced Zeeman effect. However, the controlled manipulation of anisotropic optical properties in TMDs via magnetism remains challenging. Here, the magnetic ordering in FePS3 profoundly impacts the optical characteristics of WSe2, achieving a giant linear polarization degree of 5.1 in exciton emission is demonstrated. This is supported by a detailed analysis of low-temperature photoluminescence (PL) and Raman spectra from nL-FePS3/WSe2 heterostructures. These findings indicate that a phase transition in FePS3 from paramagnetic to antiferromagnetic enhances interlayer Coulomb interactions, inducing a transition from non-polar to polar behavior in the heterostructures. Additionally, valley-polarized PL spectra under magnetic fields from -9 to 9 T reveal the influence of FePS3 on valley polarization and Zeeman splitting of excitons in monolayer WSe2. These results present a novel strategy for tailoring the optoelectronic properties of 2D magnetic van der Waals heterostructures, paving the way for advancements in nanoscale device design.

Therapeutic biomaterials with liver X receptor agonists based on the horizon of material biology to regulate atherosclerotic plaque regression in situ for devices surface engineering.

Percutaneous coronary interventional is the main treatment for coronary atherosclerosis. At present, most studies focus on blood components and smooth muscle cells to achieve anticoagulation or anti-proliferation effects, while the mediated effects of materials on macrophages are also the focus of attention. Macrophage foam cells loaded with elevated cholesterol is a prominent feature of atherosclerotic plaque. Activation of liver X receptor (LXR) to regulate cholesterol efflux and efferocytosis and reduce the number of macrophage foam cells in plaque is feasible for the regression of atherosclerosis. However, cholesterol efflux promotion remains confined to targeted therapies. Herein, LXR agonists (GW3965) were introduced on the surface of the material and delivered in situ to atherogenic macrophages to improve drug utilization for anti-atherogenic therapy and plaque regression. LXR agonists act as plaque inhibition mediated by multichannel regulation macrophages, including lipid metabolism (ABCA1, ABCG1 and low-density lipoprotein receptor), macrophage migration (CCR7) and efferocytosis (MerTK). Material loaded with LXR agonists significantly reduced plaque burden in atherosclerotic model rats, most importantly, it did not cause hepatotoxicity and adverse reactions such as restenosis and thrombosis after material implantation. Both in vivo and in vitro evaluations confirmed its anti-atherosclerotic capability and safety. Overall, multi-functional LXR agonist-loaded materials with pathological microenvironment regulation effect are expected to be promising candidates for anti-atherosclerosis and have potential applications in cardiovascular devices surface engineering.

Preparation of Time-Sequential Functionalized ZnS-ZnO Film for Modulation of Interfacial Behavior of Metals in Biological Service Environments.

Blood-contact devices are prone to inflammation, endothelial dysfunction, coagulation, and the uncontrolled release of metal ions during implantation and service. Therefore, it is essential to make these multifunctional. Herein, a superhydrophobic DE@ZnS-ZnO@SA film (composed of dabigatran ester, zinc sulfite, zinc oxide, and stearic acid, respectively) is produced. The prepared film has non-adhesion and antibacterial properties, superior mechanical stability, durability, corrosion resistance, and is self-cleaning and blood-repellent. The results of the hemolysis, cytotoxicity, and other anticoagulant experiments revealed that the film had good blood compatibility, no cytotoxicity, and excellent anticoagulant properties. The film displays anticoagulant properties even after being immersed in Phosphate-Buffered Saline (PBS) for 7 days. Furthermore, the film can spontaneously release H2S gas for 90 h after soaking in an acidic environment (pH = 6) for 90 h. This property improves the acidic microenvironment of the lesion and promotes the proliferation of endothelial cells by using H2S gas. In addition, the film can inhibit the uncontrollable release of Zn2+ ions, avoiding its toxicity even when immersed in an acid environment for 35 days. This time-sequential functionalized surface has the potential to typify the future of blood-contacting scaffolds for long-lasting use.

Drip Fertigation Increases Maize Grain Yield by Affecting Phenology, Grain Filling Process, Biomass Accumulation and Translocation: A 4-Year Field Trial.

Drip fertigation (DF) is a widely used technology to increase grain yield with water and fertilizer conservation. However, the mechanism of high grain yield (GY) under DF is still unclear. Here, a four-year field experiment assessed the impacts of four treatments (i.e., conventional irrigation and nitrogen application, CK; drip irrigation with conventional nitrogen fertilization, DI; split-nitrogen fertigation with conventional irrigation, SF; and drip fertigation, DF) on maize phenology, leaf photosynthetic rates, grain filling processes, plant biomass, and GY. The results showed that DF significantly increased maize GY by affecting phenology, grain filling traits, aboveground biomass (BIO) accumulation, and translocation. Specifically, DF significantly increased leaf chlorophyll content, which enhanced leaf photosynthetic rates, and together with an increase of leaf area index, promoted BIO accumulation. As a result, the BIO at the silking stage of DF increased by 29.5%, transported biomass increased by 109.2% (1.2 t ha-1), and the accumulation of BIO after silking increased by 23.1% (1.7 t ha-1) compared with CK. Meanwhile, DF prolonged grain filling days, significantly increased the grain weight of 100 kernels, and promoted GY increase. Compared with CK, the four-year averaged GY and BIO increased by 34.3% and 26.8% under DF; a 29.7%, 46.1%, and 24.2% GY increase and a 30.7%, 39.5%, and 29.9% BIO increase were contributed by irrigation, nitrogen, and coupling effects of irrigation and nitrogen, respectively. These results reveal the high yield mechanism of drip-fertigated maize, and are of important significance for promoting the application of drip fertigation.

A New Spectral Index for Monitoring Leaf Area Index of Winter Oilseed Rape (Brassica napus L.) under Different Coverage Methods and Nitrogen Treatments.

The leaf area index (LAI) is a crucial physiological indicator of crop growth. This paper introduces a new spectral index to overcome angle effects in estimating the LAI of crops. This study quantitatively analyzes the relationship between LAI and multi-angle hyperspectral reflectance from the canopy of winter oilseed rape (Brassica napus L.) at various growth stages, nitrogen application levels and coverage methods. The angular stability of 16 traditional vegetation indices (VIs) for monitoring the LAI was tested under nine view zenith angles (VZAs). These multi-angle VIs were input into machine learning models including support vector machine (SVM), eXtreme gradient boosting (XGBoost), and Random Forest (RF) to determine the optimal monitoring strategy. The results indicated that the back-scattering direction outperformed the vertical and forward-scattering direction in terms of monitoring the LAI. In the solar principal plane (SPP), EVI-1 and REP showed angle stability and high accuracy in monitoring the LAI. Nevertheless, this relationship was influenced by experimental conditions and growth stages. Compared with traditional VIs, the observation perspective insensitivity vegetation index (OPIVI) had the highest correlation with the LAI (r = 0.77-0.85). The linear regression model based on single-angle OPIVI was most accurate at -15° (R2 = 0.71). The LAI monitoring achieved using a multi-angle OPIVI-RF model had the higher accuracy, with an R2 of 0.77 and with a root mean square error (RMSE) of 0.38 cm2·cm-2. This study provides valuable insights for selecting VIs that overcome the angle effect in future drone and satellite applications.

Emergence of Optical Anisotropy in Moiré Superlattice via Heterointerface Engineering.

The interaction between light and moiré superlattices presents a platform for exploring unique light-matter phenomena. Tailoring these optical properties holds immense potential for advancing the utilization of moiré superlattices in photonics, optoelectronics, and valleytronics. However, the control of the optical polarization state in moiré superlattices, particularly in the presence of moiré effects, remains elusive. Here, we unveil the emergence of optical anisotropy in moiré superlattices by constructing twisted WSe2/WSe2/SiP heterostructures. We report a linear polarization degree of ∼70% for moiré excitons, attributed to the spatially nonuniform charge distribution, corroborated by first-principles calculations. Furthermore, we demonstrate the modulation of this linear polarization state via the application of a magnetic field, resulting in polarization angle rotation and a magnetic-field-dependent linear polarization degree, influenced by valley coherence and moiré potential effects. Our findings demonstrate an efficient strategy for tuning the optical polarization state of moiré superlattices using heterointerface engineering.

Carbon monoxide-releasing Vehicle CO@TPyP-FeMOFs modulating macrophages phenotype in inflammatory wound healing.

Healing of chronic wounds has been critically limited by prolonged inflammation. Carbon monoxide (CO) is a biologically active molecule with high potential based on its efficacy in modulating inflammation, promoting wound healing and tissue remodeling. Strategies to use CO as a gaseous drug to chronic wounds have emerged, but controlling the sustained release of CO at the wound site remains a major challenge. In this work, a porphyrin-Fe based metal organic frameworks, TPyP-FeMOFs was prepared. The synthesized TPyP-FeMOFs was high-temperature vacuum activated (AcTPyP-FeMOFs) and AcTPyP-FeMOFs had a relatively high Fe (II) content. CO sorption isotherms showed that AcTPyP-FeMOFs chemisorbed CO and thus CO release was sustained and prolonged. In vitro evaluation results showed that CO@TPyP-FeMOFs reduced the inflammatory level of lipopolysaccharide (LPS) activated macrophages, polarized macrophages to M2 anti-inflammatory phenotype, and promoted the proliferation of fibroblasts by altering the pathological microenvironment. In vivo study confirmed CO@TPyP-FeMOFs promoted healing in a LPS model of delayed cutaneous wound repair and reduced macrophages and neutrophils recruitment. Both in vitro and in vivo studies verified that CO@TPyP-FeMOFs acted on macrophages by modulating phenotype and inflammatory factor expression. Thus, CO release targeting macrophages and pathological microenvironment modulation presented a promising strategy for wound healing.

Anomalous Phonon Behavior and Tunable Exciton Emissions: Insights into Pressure-Driven Dynamics in Silicon Phosphide.

IV-V two-dimensional materials have emerged as key contenders for polarization-sensitive and angle-resolved devices, given their inherent anisotropic physical properties. While these materials exhibit intriguing high-pressure quasi-particle behavior and phase transition, the evolution of quasi-particles and their interactions under external pressure remain elusive. Here, employing a diamond anvil cell and spectroscopic measurements coupled with first-principles calculations, we unveil rarely observed pressure-induced phonon-phonon coupling in layered SiP flakes. This coupling manifests as an anomalous phonon hardening behavior for the A1 mode within a broad wavenumber phonon softening region. Furthermore, we demonstrate the effective tuning of exciton emissions in SiP flakes under pressure, revealing a remarkable 63% enhancement in the degree of polarization (DOP) within the pressure range of 0-3.5 GPa. These findings contribute to our understanding of high-pressure phonon evolution in SiP materials and offer a strategic approach to manipulate the anisotropic performance of in-plane anisotropic 2D materials.

Influence of Time-Lag Effects between Winter-Wheat Canopy Temperature and Atmospheric Temperature on the Accuracy of CWSI Inversion of Photosynthetic Parameters.

When calculating the CWSI, previous researchers usually used canopy temperature and atmospheric temperature at the same time. However, it takes some time for the canopy temperature (Tc) to respond to atmospheric temperature (Ta), suggesting the time-lag effects between Ta and Tc. In order to investigate time-lag effects between Ta and Tc on the accuracy of the CWSI inversion of photosynthetic parameters in winter wheat, we conducted an experiment. In this study, four moisture treatments were set up: T1 (95% of field water holding capacity), T2 (80% of field water holding capacity), T3 (65% of field water holding capacity), and T4 (50% of field water holding capacity). We quantified the time-lag parameter in winter wheat using time-lag peak-seeking, time-lag cross-correlation, time-lag mutual information, and gray time-lag correlation analysis. Based on the time-lag parameter, we modified the CWSI theoretical and empirical models and assessed the impact of time-lag effects on the accuracy of the CWSI inversion of photosynthesis parameters. Finally, we applied several machine learning algorithms to predict the daily variation in the CWSI after time-lag correction. The results show that: (1) The time-lag parameter calculated using time-lag peak-seeking, time-lag cross-correlation, time-lag mutual information, and gray time-lag correlation analysis are 44-70, 32-44, 42-58, and 76-97 min, respectively. (2) The CWSI empirical model corrected by the time-lag mutual information method has the highest correlation with photosynthetic parameters. (3) GA-SVM has the highest prediction accuracy for the CWSI empirical model corrected by the time-lag mutual information method. Considering time lag effects between Ta and Tc effectively enhanced the correlation between CWSI and photosynthetic parameters, which can provide theoretical support for thermal infrared remote sensing to diagnose crop water stress conditions.

Multi-Objective Process Parameter Optimization of Ultrasonic Rolling Combining Machine Learning and Non-Dominated Sorting Genetic Algorithm-II.

Ultrasonic rolling is an effective technique for enhancing surface integrity, and surface integrity is closely related to fatigue performance. The process parameters of ultrasonic rolling critically affect the improvement of surface integrity. This study proposes an optimization method for process parameters by combining machine learning (ML) with the NSGA-II. Five ML models were trained to establish relationships between process parameters and surface residual stress, hardness, and surface roughness by incorporating feature augmentation and physical information. The best-performing model was selected and integrated with NSGA-II for multi-objective optimization. Ultrasonic rolling tests based on a uniform design were performed, and a dataset was established. The objective was to maximize surface residual stress and hardness while minimizing surface roughness. For test specimens with an initial surface roughness of 0.54 µm, the optimized process parameters were a static pressure of 900 N, a spindle speed of 75 rpm, a feed rate of 0.19 mm/r, and rolling once. Using optimized parameters, the surface residual stress reached -920.60 MPa, surface hardness achieved 958.23 HV, surface roughness reduced to 0.32 µm, and contact fatigue life extended to 3.02 × 107 cycles, representing a 52.5% improvement compared to untreated specimens and an even more significant improvement over without parameter optimization.

Diagnostic yield using electromagnetic navigation bronchoscopy for peripheral pulmonary nodules <2 cm.

BACKGROUND: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. OBJECTIVES: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. DESIGN: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. METHODS: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. RESULTS: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010). CONCLUSION: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

Integrative multiomics analysis identifies molecular subtypes and potential targets of hepatocellular carcinoma.

BACKGROUND: The liver is anatomically divided into eight segments based on the distribution of Glisson's triad. However, the molecular mechanisms underlying each segment and its association with hepatocellular carcinoma (HCC) heterogeneity are not well understood. In this study, our objective is to conduct a comprehensive multiomics profiling of the segmentation atlas in order to investigate potential subtypes and therapeutic approaches for HCC. METHODS: A high throughput liquid chromatography-tandem mass spectrometer strategy was employed to comprehensively analyse proteome, lipidome and metabolome data, with a focus on segment-resolved multiomics profiling. To classify HCC subtypes, the obtained data with normal reference profiling were integrated. Additionally, potential therapeutic targets for HCC were identified using immunohistochemistry assays. The effectiveness of these targets were further validated through patient-derived organoid (PDO) assays. RESULTS: A multiomics profiling of 8536 high-confidence proteins, 1029 polar metabolites and 3381 nonredundant lipids was performed to analyse the segmentation atlas of HCC. The analysis of the data revealed that in normal adjacent tissues, the left lobe was primarily involved in energy metabolism, while the right lobe was associated with small molecule metabolism. Based on the normal reference atlas, HCC patients with segment-resolved classification were divided into three subtypes. The C1 subtype showed enrichment in ribosome biogenesis, the C2 subtype exhibited an intermediate phenotype, while the C3 subtype was closely associated with neutrophil degranulation. Furthermore, using the PDO assay, exportin 1 (XPO1) and 5-lipoxygenase (ALOX5) were identified as potential targets for the C1 and C3 subtypes, respectively. CONCLUSION: Our extensive analysis of the segmentation atlas in multiomics profiling defines molecular subtypes of HCC and uncovers potential therapeutic strategies that have the potential to enhance the prognosis of HCC.

18ß-glycyrrhetinic acid alleviates radiation-induced skin injury by activating the Nrf2/HO-1 signaling pathway.

Radiation-induced skin injury is a common side effect of radiotherapy, but there are few therapeutic drugs available for prevention or treatment. In this study, we demonstrate that 18ß-Glycyrrhetinic acid (18ß-GA), a bioactive component derived from Glycyrrhiza glabra, substantially reduces the accumulation of reactive oxygen species (ROS) and inhibits apoptosis in HaCaT cells after ionizing radiation (IR), thereby mitigating radiation-induced skin injury. Mechanistically, 18ß-GA promotes the nuclear import of Nrf2, leading to activation of the Nrf2/HO-1 signaling pathway in response to IR. Importantly, Nrf2 silencing increases cell apoptosis and reverse the protective effect of 18ß-GA on radiation-induced skin injury. Furthermore, 18ß-GA preserves skin tissue structure after irradiation, inhibits inflammatory cell infiltration, and alleviates radiation dermatitis. In conclusion, our results suggest that 18ß-GA reduces intracellular ROS production and apoptosis by activating the Nrf2/HO-1 signaling pathway, leading to amelioration of radiation dermatitis.

Deep Learning-Enhanced Hand Grip and Release Test for Degenerative Cervical Myelopathy: Shortening Assessment Duration to 6 Seconds.

OBJECTIVE: Hand clumsiness and reduced hand dexterity can signal early signs of degenerative cervical myelopathy (DCM). While the 10-second grip and release (10-s G&R) test is a common clinical tool for evaluating hand function, a more accessible method is warranted. This study explores the use of deep learning-enhanced hand grip and release test (DL-HGRT) for predicting DCM and evaluates its capability to reduce the duration of the 10-s G&R test. METHODS: The retrospective study included 508 DCM patients and 1,194 control subjects. Propensity score matching (PSM) was utilized to minimize the confounding effects related to age and sex. Videos of the 10-s G&R test were captured using a smartphone application. The 3D-MobileNetV2 was utilized for analysis, generating a series of parameters. Additionally, receiver operating characteristic curves were employed to assess the performance of the 10-s G&R test in predicting DCM and to evaluate the effectiveness of a shortened testing duration. RESULTS: Patients with DCM exhibited impairments in most 10-s G&R test parameters. Before PSM, the number of cycles achieved the best diagnostic performance (area under the curve [AUC], 0.85; sensitivity, 80.12%; specificity, 74.29% at 20 cycles), followed by average grip time. Following PSM for age and gender, the AUC remained above 0.80. The average grip time achieved the highest AUC of 0.83 after 6 seconds, plateauing with no significant improvement in extending the duration to 10 seconds, indicating that 6 seconds is an adequate timeframe to efficiently evaluate hand motor dysfunction in DCM based on DL-HGRT. CONCLUSION: DL-HGRT demonstrates potential as a promising supplementary tool for predicting DCM. Notably, a testing duration of 6 seconds appears to be sufficient for accurate assessment, enhancing the test more feasible and practical without compromising diagnostic performance.

Deep learning-based label-free imaging of lymphatics and aqueous veins in the eye using optical coherence tomography.

We demonstrate an adaptation of deep learning for label-free imaging of the micro-scale lymphatic vessels and aqueous veins in the eye using optical coherence tomography (OCT). The proposed deep learning-based OCT lymphangiography (DL-OCTL) method was trained, validated and tested, using OCT scans (23 volumetric scans comprising 19,736 B-scans) from 11 fresh ex vivo porcine eyes with the corresponding vessel labels generated by a conventional OCT lymphangiography (OCTL) method based on thresholding with attenuation compensation. Compared to conventional OCTL, the DL-OCTL method demonstrates comparable results for imaging lymphatics and aqueous veins in the eye, with an Intersection over Union value of 0.79 ± 0.071 (mean ± standard deviation). In addition, DL-OCTL mitigates the imaging artifacts in conventional OCTL where the OCT signal modelling was corrupted by the tissue heterogeneity, provides ~ 10 times faster processing based on a rough comparison and does not require OCT-related knowledge for correct implementation as in conventional OCTL. With these favorable features, DL-OCTL promises to improve the practicality of OCTL for label-free imaging of lymphatics and aqueous veins for preclinical and clinical imaging applications.

SYT7 (synaptotagmin 7) promotes cervical squamous cell carcinoma.

Cervical squamous cell carcinoma (CESC) ranks among the primary contributors to global cancer-associated mortality. However, the role mediated by synaptotagmin 7 (SYT7) in CESC remains unclear. Our study employed immunohistochemistry to assess the level of SYT7 expression in the tissue microarray. Furthermore, lentiviral shRNA transduction was utilized to establish SYT7 knockdown cell line models based on HeLa and SiHa cell lines. The functional impacts of silencing SYT7 expression in vitro were evaluated. A subcutaneous xenograft model was employed to examine the tumorigenic potential of cells with or without SYT7. The content of SYT7 in CESC tissues was significantly elevated compared to adjacent normal tissues. Functionally, silencing SYT7 in HeLa and SiHa cells suppressed cell proliferation, colony formation ability, and apoptosis enhancement. Additionally, cells with suppressed SYT7 also exhibited inhibited cell migration and invasion. In vivo experiments demonstrated the loss of tumorigenic ability in SYT7 knockdown cells and suppressed tumor growth. Quantitative PCR PrimeView PathArray and apoptosis antibody array analyses revealed that upon elimination of SYT7, there was a significant upregulation observed in Caspase 8, TNF-R1 (TNF receptor superfamily member 1A), and HSPA5 (heat shock protein family A [Hsp70] member 5), while TGFBI (transforming growth factor beta-induced), RPL31 (ribosomal protein L31), LUM (lumican), HSDL2 (hydroxysteroid dehydrogenase-like 2), ITGB5 (integrin subunit beta 5), and Smad2 (SMAD family member2) were downregulated. Overall, we have demonstrated the tumor-promoting functions of SYT7 in CESC.

Multifunctional nanocoatings with synergistic controlled release of zinc ions and cytokines for precise modulation of vascular intimal reconstruction.

Vascular stent implantation remains the major therapeutic method for cardiovascular diseases currently. We here introduced crucial biological functional biological function factors (SDF-1α, VEGF) and vital metal ions (Zn2+) into the stent surface to explore their synergistic effect in the microenvironment. The combination of the different factors is known to effectively regulate cellular inflammatory response and selectively regulate cell biological behavior. Meanwhile, in the implemented method, VEGF and Zn2+ were loaded into heparin and poly-l-lysine (Hep-PLL) nanoparticles, ensuring a controlled release of functional molecules with a multi-factor synergistic effect and excellent biological functions in vitro and in vivo. Notably, after 150 days of implantation of the modified stent in rabbits, a thin and smooth new intima was obtained. This study offers a new idea for constructing a modified surface microenvironment and promoting tissue repair.