Tunable and highly sensitive fluorescent thermometers from La2CaZrO6:Cr3+ with a time-resolved technology.

Non-contact optical temperature measurement can effectively avoid the disadvantages of traditional contact thermometry and thus, become a hot research topic. Herein, a fluorescence intensity ratio (FIR) thermometry using a time-resolved technique based on La2CaZrO6:Cr3+ (LCZO) is proposed, with a maximum relative sensitivity (Sr - FIR) of 2.56% K-1 at 473 K and a minimum temperature resolution of 0.099 K. Moreover, the relative sensitivity and temperature resolution can be effectively controlled by adjusting the width of the time gate based on the time-resolved technique. Our work provides, to our knowledge, new viewpoints into the development of novel optical thermometers with adjustable relative sensitivity and temperature resolution on an as-needed basis.

Rigid CuInS2/ZnS Core/Shell Quantum Dots for High Performance Infrared Light-Emitting Diodes.

CuInS2 (CIS) quantum dots (QDs) represent an important class of colloidal materials with broad application potential, owing to their low toxicity and unique optical properties. Although coating with a ZnS shell has been identified as a crucial method to enhance optical performance, the occurrence of cation exchange has historically resulted in the unintended formation of Cu-In-Zn-S alloyed QDs, causing detrimental blueshifts in both absorption and photoluminescence (PL) spectral profiles. In this study, we present a facile one-pot synthetic strategy aimed at impeding the cation exchange process and promoting ZnS shell growth on CIS core QDs. The suppression of both electron-phonon interaction and Auger recombination by the rigid ZnS shell results in CIS/ZnS core/shell QDs that exhibit a wide near-infrared (NIR) emission coverage and a remarkable PL quantum yield of 92.1%. This effect boosts the fabrication of high-performance, QD-based NIR light-emitting diodes with the best stability of such materials so far.

CylinGCN: Cylindrical structures segmentation in 3D biomedical optical imaging by a contour-based graph convolutional network.

Cylindrical organs, e.g., blood vessels, airways, and intestines, are ubiquitous structures in biomedical optical imaging analysis. Image segmentation of these structures serves as a vital step in tissue physiology analysis. Traditional model-driven segmentation methods seek to fit the structure by constructing a corresponding topological geometry based on domain knowledge. Classification-based deep learning methods neglect the geometric features of the cylindrical structure and therefore cannot ensure the continuity of the segmentation surface. In this paper, by treating the cylindrical structures as a 3D graph, we introduce a novel contour-based graph neural network for 3D cylindrical structure segmentation in biomedical optical imaging. Our proposed method, which we named CylinGCN, adopts a novel learnable framework that extracts semantic features and complex topological relationships in the 3D volumetric data to achieve continuous and effective 3D segmentation. Our CylinGCN consists of a multiscale 3D semantic feature extractor for extracting inter-frame multiscale semantic features, and a residual graph convolutional network (GCN) contour generator that combines the semantic features and cylindrical topological priors to generate segmentation contours. We tested the CylinGCN framework on two types of optical tomographic imaging data, small animal whole body photoacoustic tomography (PAT) and endoscopic airway optical coherence tomography (OCT), and the results show that CylinGCN achieves state-of-the-art performance. Code will be released at https://github.com/lzc-smu/CylinGCN.git.

Effect of tumor exosome-derived Lnc RNA HOTAIR on the growth and metastasis of gastric cancer

Purpose HOX transcribed antisense RNA (HOTAIR) is a long noncoding RNA (LncRNA) that promotes tumor progression. Exosomes are critically involved in cancer progression. The presence of HOTAIR in the circulating exosomes and the roles of exosomal HOTAIR in gastric cancer (GC) remains unknown. This study aimed to investigate the role of HOTAIR in exosomes in promoting the growth and metastasis of GC. Methods Serum exosomes from GC patients were captured by CD63 immunoliposome magnetic spheres (CD63-IMS), and the biological characteristics of the exosomes were identified. The expression levels of HOTAIR in GC cells, tissues, serum and serum exosomes were detected by fluorescence quantitative PCR (qRT-PCR), and the clinicopathological correlation was statistically analyzed. The growth and metastasis abilities of GC cells with HOTAIR knockdown in vitro were evaluated by cell experiment. The effects of HOTAIR highly-expressed NCI-N87 cell-derived exosomes were used to treat HOTAIR lowly-expressed MKN45 cells on GC growth and metastasis were also evaluated. Results The exosomes isolated by CD63-IMS had a particle size of 89.78 ± 4.8 nm and were oval membranous particles. The expression of HOTAIR in tumor tissues and serum of GC patients was increased (P < 0.05), and the expression of HOTAIR in serum exosomes was significantly increased (P < 0.01). The in NCI-N87 and MKN45 cell experiment demonstrated that HOTAIR knockdown by RNA interference suppressed cell growth and metastasis in NCI-N87 cells. Coculture of exosomes secreted by NCI-N87 cells with MKN45 cells significantly increased the expression of HOTAIR, and enhanced cell growth and metastasis. Conclusion LncRNA HOTAIR can be used as a potential biomarker which provides a new way for the diagnosis and treatment of GC (AU)

Unsupervised Fusion of Misaligned PAT and MRI Images via Mutually Reinforcing Cross-Modality Image Generation and Registration.

Photoacoustic tomography (PAT) and magnetic resonance imaging (MRI) are two advanced imaging techniques widely used in pre-clinical research. PAT has high optical contrast and deep imaging range but poor soft tissue contrast, whereas MRI provides excellent soft tissue information but poor temporal resolution. Despite recent advances in medical image fusion with pre-aligned multimodal data, PAT-MRI image fusion remains challenging due to misaligned images and spatial distortion. To address these issues, we propose an unsupervised multi-stage deep learning framework called PAMRFuse for misaligned PAT and MRI image fusion. PAMRFuse comprises a multimodal to unimodal registration network to accurately align the input PAT-MRI image pairs and a self-attentive fusion network that selects information-rich features for fusion. We employ an end-to-end mutually reinforcing mode in our registration network, which enables joint optimization of cross-modality image generation and registration. To the best of our knowledge, this is the first attempt at information fusion for misaligned PAT and MRI. Qualitative and quantitative experimental results show the excellent performance of our method in fusing PAT-MRI images of small animals captured from commercial imaging systems.

Automatic 3D reconstruction of an anatomically correct upper airway from endoscopic long range OCT images.

Endoscopic airway optical coherence tomography (OCT) is a non-invasive and high resolution imaging modality for the diagnosis and analysis of airway-related diseases. During OCT imaging of the upper airway, in order to reliably characterize its 3D structure, there is a need to automatically detect the airway lumen contour, correct rotational distortion and perform 3D airway reconstruction. Based on a long-range endoscopic OCT imaging system equipped with a magnetic tracker, we present a fully automatic framework to reconstruct the 3D upper airway model with correct bending anatomy. Our method includes an automatic segmentation method for the upper airway based on dynamic programming algorithm, an automatic initial rotation angle error correction method for the detected 2D airway lumen contour, and an anatomic bending method combined with the centerline detected from the magnetically tracked imaging probe. The proposed automatic reconstruction framework is validated on experimental datasets acquired from two healthy adults. The result shows that the proposed framework allows the full automation of 3D airway reconstruction from OCT images and thus reveals its potential to improve analysis efficiency of endoscopic OCT images.

Study on the mechanism of high energy transfer efficiency of blue light excited Cr3+, Nd3+ co-doped near infrared phosphors.

Although Cr3+ as activator for Near infrared (NIR) phosphors has been widely studied, the peaks of Cr3+ emission spectra in most hosts are less than 1000 nm. Nd3+ as an activator in many hosts has a wide distribution of absorption peaks in the Ultraviolet-visible-Near infrared (UV-vis-NIR) band, especially in the 650-900 nm band for effective NIR to NIR Stokes luminescence (4F3/2→4I9/2, 4F3/2→4I11/2 transitions). Therefore, Cr3+, Nd3+ co-doping to achieve the emission in the NIR II region (1000-1700nm) is very meaningful. Here, we report La2CaZrO6(LCZO): Cr3+, Nd3+ NIR phosphors with emission spectra covering an ultra-wide range of 700-1400 nm and reveal their luminescence mechanism. The energy transfer efficiency of Cr3+ for Nd3+ can be as high as 88.4% under 471 nm blue light excitation. In the same case, the integrated intensity of the emission spectra of Cr3+, Nd3+ co-doped can reach 847% of that of Nd3+ alone and 204% of that of Cr3+ alone. Finally, the combination of commercial blue light chips and Cr3+, Nd3+ co-doped NIR phosphors shows great potential for applications in face recognition, night lighting, and angiography.

Learning spatially variant degradation for unsupervised blind photoacoustic tomography image restoration.

Photoacoustic tomography (PAT) images contain inherent distortions due to the imaging system and heterogeneous tissue properties. Improving image quality requires the removal of these system distortions. While model-based approaches and data-driven techniques have been proposed for PAT image restoration, achieving accurate and robust image recovery remains challenging. Recently, deep-learning-based image deconvolution approaches have shown promise for image recovery. However, PAT imaging presents unique challenges, including spatially varying resolution and the absence of ground truth data. Consequently, there is a pressing need for a novel learning strategy specifically tailored for PAT imaging. Herein, we propose a configurable network model named Deep hybrid Image-PSF Prior (DIPP) that builds upon the physical image degradation model of PAT. DIPP is an unsupervised and deeply learned network model that aims to extract the ideal PAT image from complex system degradation. Our DIPP framework captures the degraded information solely from the acquired PAT image, without relying on ground truth or labeled data for network training. Additionally, we can incorporate the experimentally measured Point Spread Functions (PSFs) of the specific PAT system as a reference to further enhance performance. To evaluate the algorithm's effectiveness in addressing multiple degradations in PAT, we conduct extensive experiments using simulation images, publicly available datasets, phantom images, and in vivo small animal imaging data. Comparative analyses with classical analytical methods and state-of-the-art deep learning models demonstrate that our DIPP approach achieves significantly improved restoration results in terms of image details and contrast.

Surgical resection for second primary colorectal cancer: a population-based study.

Background: Second primary colorectal cancer (CRC) is attributed to a crucial component of the CRC population. Still, its treatments remain unclear due to the troublesome conditions originating from multiple primary cancers and the lack of quality evidence. This study aimed to determine that which type of surgical resection is the eligible treatment for second primary CRC among patients with a prior cancer history. Methods: This cohort study retrospectively collected patients with second primary stage 0-III CRC in the Surveillance, Epidemiology, and End Results database from 2000 to 2017. Prevalence of surgical resection in second primary CRC, overall survival (OS) and disease-specific survival (DSS) of patients who received different surgical interventions were estimated. Results: A total of 38,669 patients with second primary CRC were identified. Most of the patients (93.2%) underwent surgical resection as initial treatment. Approximately 39.2% of the second primary CRCs (N = 15,139) were removed with segmental resection, while 54.0% (N = 20,884) were removed through radical colectomy/proctectomy. Surgical resection was associated with a significantly favorable OS and DSS compared to those not receiving any surgical operations for second primary CRC [OS: adjusted Hazard ratios (adjusted HR): 0.35; 95% CI: 0.34-0.37, p < 0.001; DSS: adjusted HR: 0.27; 95% CI: 0.25-0.29, p < 0.001]. Segmental resection considerably outperformed radical resection in terms of OS and DSS (OS: adjusted HR: 0.97; 95% CI: 0.91-1.00, p = 0.07; DSS: adjusted HR: 0.92; 95% CI: 0.87-0.97, p = 0.002). Segmental resection was also associated with a significantly reduced cumulative mortality of postoperative non-cancer comorbidities. Conclusion: Surgical resection demonstrated excellent oncological superiority for second primary CRC and was used to remove the vast majority of second primary CRCs. In comparison to radical resection, segmental resection offered a better prognosis and reduced postoperative non-cancer complications. The second primary colorectal cancers should be resected if the patients can afford surgical operations.

Correlation analysis of the expression of mesenchymal circulating tumor cells and CD133 with the prognosis of colorectal cancer.

OBJECTIVE: To evaluate the expression of tumor stem cell marker CD133 in peripheral blood circulating tumor cells (CTC) and the value of CD133 in prognosis of patients with colorectal cancer (CRC). METHODS: Preoperative/pre-chemotherapy peripheral blood samples of 63 patients with CRC from January 2016 to January 2021 were selected to detect peripheral blood CTC by CanPatrol CTC enrichment technology. Expression of CD133 in different epithelial-mesenchymal transition (EMT) typing CTC was analyzed. Clinical data (including tumor size, tumor stage, pathological typing, molecular typing, lymph node metastasis, distant metastasis, carcinoembryonic antigen (CEA), and CA-199 expression), PFS time and OS time were followed up. The expression of CD133 in different CTCs was compared, and the correlation between CD133 and patient survival time was compared. RESULTS: The positive rate of E-CTC in patients with tumor diameter ≥5 cm was significantly higher than that of patients with tumor diameter <5 cm (P=0.035). The positive rate of M-CTC in patients with diabetes was significantly higher than that of patients without diabetes (P=0.006). The CD133-positive M-CTCs were significantly higher in DM and CEA>5 ng/mL patients than in non-DM and CEA≤5 ng/mL patients (P<0.001, P=0.0195). Fifty-five patients were followed up for a median of 14 months. During follow-up, 19 had disease progression and five died. According to the cutoff point obtained by ROC analysis, the PFS of M-CTC>2.5/5 ml patients (0%) was lower than that of ≤2.5/5 ml patients (76.5%), P<0.05. PFS in patients with CD133-positive M-CTC>0.5/5 mL (18.6%) was lower than in patients with ≤0.5/5 ml (76.5%), P<0.05. However, thedifference in the OS between patients with CD133-positive M-CTC>0.5/5 ml (71.7%) and those with ≤0.5/5 ml (93.8%), was not significant, P=0.054. CONCLUSION: CD133 positive M-CTC is closely related to distant metastasis in CRC. The expression of CD133 in CTC, especially in M-CTC, can be used as a prognostic indicator for colorectal cancer.

Effect of tumor exosome-derived Lnc RNA HOTAIR on the growth and metastasis of gastric cancer.

PURPOSE: HOX transcribed antisense RNA (HOTAIR) is a long noncoding RNA (LncRNA) that promotes tumor progression. Exosomes are critically involved in cancer progression. The presence of HOTAIR in the circulating exosomes and the roles of exosomal HOTAIR in gastric cancer (GC) remains unknown. This study aimed to investigate the role of HOTAIR in exosomes in promoting the growth and metastasis of GC. METHODS: Serum exosomes from GC patients were captured by CD63 immunoliposome magnetic spheres (CD63-IMS), and the biological characteristics of the exosomes were identified. The expression levels of HOTAIR in GC cells, tissues, serum and serum exosomes were detected by fluorescence quantitative PCR (qRT-PCR), and the clinicopathological correlation was statistically analyzed. The growth and metastasis abilities of GC cells with HOTAIR knockdown in vitro were evaluated by cell experiment. The effects of HOTAIR highly-expressed NCI-N87 cell-derived exosomes were used to treat HOTAIR lowly-expressed MKN45 cells on GC growth and metastasis were also evaluated. RESULTS: The exosomes isolated by CD63-IMS had a particle size of 89.78 ± 4.8 nm and were oval membranous particles. The expression of HOTAIR in tumor tissues and serum of GC patients was increased (P < 0.05), and the expression of HOTAIR in serum exosomes was significantly increased (P < 0.01). The in NCI-N87 and MKN45 cell experiment demonstrated that HOTAIR knockdown by RNA interference suppressed cell growth and metastasis in NCI-N87 cells. Coculture of exosomes secreted by NCI-N87 cells with MKN45 cells significantly increased the expression of HOTAIR, and enhanced cell growth and metastasis. CONCLUSION: LncRNA HOTAIR can be used as a potential biomarker which provides a new way for the diagnosis and treatment of GC.

Two-Dimensional Cs2 AgInx Bi1- x Cl6 Alloyed Double Perovskite Nanoplatelets for Solution-Processed Light-Emitting Diodes.

Lead-free double perovskites have emerged as a promising class of materials with potential to be integrated into a wide range of optical and optoelectronic applications. Herein, the first synthesis of 2D Cs2 AgInx Bi1- x Cl6 (0 ≤ x ≤ 1) alloyed double perovskite nanoplatelets (NPLs) with well controlled morphology and composition is demonstrated. The obtained NPLs show unique optical properties with the highest photoluminescence quantum yield of 40.1%. Both temperature dependent spectroscopic studies and density functional theory calculation results reveal that the morphological dimension reduction and In-Bi alloying effect together boost the radiative pathway of the self-trapped excitons of the alloyed double perovskite NPLs. Moreover, the NPLs exhibit good stability under ambient conditions and against polar solvents, which is ideal for all solution-processing of the materials in low-cost device manufacturing. The first solution-processed light-emitting diodes is demonstrated using the Cs2 AgIn0.9 Bi0.1 Cl6 alloyed double perovskite NPLs as the sole emitting component, showing luminance maximum of 58 cd m-2 and peak current efficiency of 0.013 cd A-1 . This study sheds light on morphological control and composition-property relationships of double perovskite nanocrystals, paving the way toward ultimate utilizations of lead-free perovskite materials in diverse sets of real-life applications.

Effect of Sr2+ ions on the structure, up-conversion emission and thermal sensing of Er3+, Yb3+ co-doped double perovskite Ba(2-x)SrxMgWO6 phosphors.

Investigating the effect of different phases on the optical performance is crucial for thermal sensing phosphor materials. Ba(2-x)SrxMgWO6:Er3+, Yb3+, K+ double perovskite phosphors were successfully prepared using a high-temperature solid-phase method. The dominant up-conversion luminescent (UCL) mechanism was deduced by analyzing the power-dependence spectra and energy level diagrams. By X-ray diffraction tests and tolerance factor calculations, it was demonstrated that the substitution of Sr2+ ions for Ba2+ ions led to the phase changing from cubic to tetragonal. The phase transition led to a decrease in the crystallographic symmetry of the compounds and changes in the optical thermometric properties. The optical temperature sensing properties were investigated using the fluorescence intensity ratio of thermally coupled energy levels (2H11/2 and 4S3/2 to the ground state energy level 4I15/2) of Er3+ ions in Ba2MgWO6, BaSrMgWO6 and Sr2MgWO6. The maximum absolute sensitivities obtained for Ba2MgWO6, BaSrMgWO6 and Sr2MgWO6 doped with 7% Er3+, 2% Yb3+ and 9% K+ were 6.77 × 10-4 K-1, 10.09 × 10-4 K-1 and 23.4 × 10-4 K-1, respectively. The comparison revealed that the phase transition caused an increase in the luminescence intensity and absolute sensitivity. This provides a useful pathway for modulating the subsequent thermometric performance.

Sr/Ba substitution induced higher thermal stability far red-emitting Ba1-ySryLaLiWO6:Mn4+ phosphors for plant growth applications.

A series of red-emitting BaLaLiWO6:Mn4+ (BLLW:Mn4+) phosphors were successfully synthesized by a high-temperature solid-state reaction method. The crystal structure and luminescence properties of the obtained samples were systematically investigated. The emission spectra exhibited a deep red emission band peaking at 716 nm with a full width at half-maximum (FWHM) of 44 nm under 340 nm excitation. The optimal Mn4+ molar concentration was about 1.2%. In addition, the luminescence mechanism was analyzed using a Tanabe Sugano energy level diagram. With the substitution of Sr for Ba, there was a red shift in the emission spectrum and a blue shift in the excitation spectrum. The emission intensity of BLLW:1.2%Mn4+ at 150 °C was about 22% of the initial value at room temperature. In contrast, the emission intensity of SrLaLiWO6:1.2%Mn4+ still maintained 79% of the initial emission intensity at room temperature at 150 °C. This was due to the fact that with the substitution of Sr for Ba, the W-O bond length gradually decreases, which gradually enhanced the crystal field strength of Mn4+.

Apple preload increased postprandial insulin sensitivity of a high glycemic rice meal only at breakfast.

PURPOSE: The possible impact of preload food on insulin sensitivity has yet been reported. This study aimed to investigate the glycemic and insulinemic effect of an apple preload before breakfast, lunch and early supper, based on high glycemic index (GI) rice meals. METHODS: Twenty-three healthy participants in Group 1 and 14 participants in Group 2 were served with the reference meal (white rice containing 50 g of available carbohydrate) or experimental meals (apple preload and rice, each containing 15 and 35 g of available carbohydrate). The meals were either served at 8:00 for breakfast, 12:30 for lunch or 17:00 for early supper to explore the possible effect of time factor. The group 1 assessed the postprandial and subsequent-meal glycemic effect of the test meals by continuous glucose monitoring (CGM), along with subjective appetite; The group 2 further investigated the glycemic and insulin effect by blood collection. RESULTS: The apple preload lowered the blood glucose peak value by 33.5%, 31.4% and 31.0% in breakfast, lunch and supper, respectively, while increased insulin sensitivity by 40.5% only at breakfast, compared with the rice reference. The early supper resulted significantly milder glycemic response than its breakfast and lunch counterparts did. The result of CGM tests was consistent with that of the fingertip blood tests. CONCLUSION: Apple preload performed the best at breakfast in terms of enhancing the insulin sensitivity. The preload treatment could effectively attenuate postprandial GR without increasing the area under insulin response curve in any of the three meals.

Classification of precancerous lesions based on fusion of multiple hierarchical features.

PURPOSE: To investigate an identification method for precancerous gastric cancer based on the fusion of superficial features and deep features of gastroscopic images. The purpose of this study is to make most use of superficial features and deep features to provide clinicians with clinical decision support to assist the diagnosis of precancerous gastric diseases and reduce the workload of doctors. METHODS: According to the nature of gastroscopic images, 75-dimensional shallow features were manually designed, including histogram features, texture features and high-order features of the image; then, based on the constructed convolutional neural networks such as ResNet and GoogLeNet, before the output layer. A fully connected layer is added as the deep feature of the image. In order to ensure consistent feature weights, the number of neurons in the fully connected layer is designed to be 75 dimensions. Therefore, the superficial and deep features of the image are concatenated, and a machine learning classifier is used to identify gastric polyps, there are three types of gastric precancerous diseases such as gastric polyps, gastric ulcers and gastric erosions. RESULTS: A dataset with 420 images was collected for each disease, and divided into a training set and a test set with a ratio of 5:1, and then based on the dataset, three methods, such as traditional machine learning, deep learning, and feature fusion, were used respectively. For model training and testing of traditional machine learning and feature fusion, SVM, RF and BP neural network are used as the classification results of the classifier. For deep learning, the GoogLeNet, ResNet, and ResNeXt were implemented. The test results of the model on the test set show that the recognition accuracy of the proposed feature fusion method reaches (SVM: 85.18%; RF: 83.42%; BPNN: 85.18%), which is better than the traditional machine learning method (SVM: 80.17%; RF: 82.37%; BPNN: 84.12%) and the deep learning method (GoogLeNet: 82.54%; ResNet-18: 81.67%; ResNet-50: 81.67%; ResNeXt-50: 82.11%), which proves that this method has obvious advantages. CONCLUSION: This study provides a new strategy for the identification of precancerous gastric cancer, improving the efficiency and accuracy of precancerous gastric cancer identification, and hopes to provide substantial practical help for the identification of gastric precancerous diseases.

Status of research on natural protein tyrosine phosphatase 1B inhibitors as potential antidiabetic agents: Update.

Protein tyrosine phosphatase 1B (PTP1B) is a crucial therapeutic target for multiple human diseases comprising type 2 diabetes (T2DM) and obesity because it is a seminal part of a negative regulator in both insulin and leptin signaling pathways. PTP1B inhibitors increase insulin receptor sensitivity and have the ability to cure insulin resistance-related diseases. However, the few PTP1B inhibitors that entered the clinic (Ertiprotafib, ISIS-113715, Trodusquemine, and JTT-551) were discontinued due to side effects or low selectivity. Molecules with broad chemical diversity extracted from natural products have been reported to be potent PTP1B inhibitors with few side effects. This article summarizes the recent PTP1B inhibitors extracted from natural products, clarifying the current research progress, and providing new options for designing new and effective PTP1B inhibitors.

Efficacy, safety, and predictors of fruquintinib plus anti-programmed death receptor-1 (PD-1) antibody in refractory microsatellite stable metastatic colorectal cancer in a real-world setting: a retrospective cohort study.

Background: Patients with microsatellite stable (MSS) advanced colorectal cancer (CRC) have few alternatives for salvage therapy and a large unmet clinical need. Preclinical studies demonstrate that fruquintinib combined with anti-programmed death protein 1 (PD-1) has a synergistic anti-tumor effect. But a few phase 2 clinical studies show inconsistent efficacy of this combination therapy in CRC. The aim of this study was to investigate the efficacy, safety, and predictors of fruquintinib plus PD-1 antibodies in refractory MSS metastatic CRC (mCRC) in a real-world setting. Methods: We performed a retrospective single-center analysis to assess the outcomes of patients with MSS mCRC who were treated with fruquintinib plus anti-PD-1 antibodies subsequent to the failure of standard therapies at the Hunan Cancer Hospital. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were reviewed and evaluated. The primary endpoint was OS. The impact on OS and PFS was examined using the Cox regression model. Results: Between 1 January 2019 and 30 June 2022, we enrolled 70 eligible patients. The median follow-up was 17.2 months (range, 5.3-32.9 months). The median OS (mOS) and median PFS (mPFS) were 19.48 and 5.5 months respectively. The ORR was 11.43% and the DCR was 84.29%. Multivariate Cox regression analysis reveals liver metastasis (LM) without local treatment was a risk factor for OS [hazard ratio (HR) =5.31, P=0.0184], whereas that with local treatment (HR =2.19, P=0.263) was not. The most common adverse events were hand-foot syndrome (37.14%), hypertension (34.29%), mucositis oral (32.86%). No serious adverse effects or adverse effect-related deaths were reported. There were no instances of severe adverse effects or deaths related to adverse effects reported. Conclusions: Our study indicates that the combination of fruquintinib and anti-PD-1 antibodies can improve the OS and PFS with a tolerable toxicity profile for Chinese patients with refractory MSS mCRC. LM without local therapy is a negative prognostic factor for OS, but those with local treatment can significantly prolong survival. We require additional well-structured, prospective, and extensive studies to confirm and validate these findings.

The Effect of Cu Addition on the Precipitation Sequence in the Al-Si-Mg-Cr Alloy.

In this work, the effect of Cu additives and heat treatment on the precipitation sequence of an Al-Si-Mg-Cr alloy has been systematically studied by means of advanced spherical aberration-corrected electron microscopy. Cu atoms tend to gather at the interface between the precipitates and the matrix at the beginning of the aging process. Then, Cu atoms diffuse into the precipitates. Two types of GP zones are formed in the first stage of precipitation: one is the type I GP zone and the other is the type II GP zone. The type I GP zone ßCu″ evolved into the Q' phase, while the type II GP zone evolved into the θ' phase during the aging process. The aging sequence of the Al-Si-Mg-Cr alloy can be determined as a supersaturated solid solution (SSSS) → GP zones → ß″→ ß'/B'(→ß). The aging sequence of the Al-7%Si-0.3%Mg-0.3%Cr-1.5%Cu alloy can be determined as a supersaturated solid solution (SSSS)→GP zone→ßCu″→Q' + θ'(→Q + θ).

Hotspot mutations in the structured ENL YEATS domain link aberrant transcriptional condensates and cancer.

Growing evidence suggests prevalence of transcriptional condensates on chromatin, yet their mechanisms of formation and functional significance remain largely unclear. In human cancer, a series of mutations in the histone acetylation reader ENL create gain-of-function mutants with increased transcriptional activation ability. Here, we show that these mutations, clustered in ENL's structured acetyl-reading YEATS domain, trigger aberrant condensates at native genomic targets through multivalent homotypic and heterotypic interactions. Mechanistically, mutation-induced structural changes in the YEATS domain, ENL's two disordered regions of opposing charges, and the incorporation of extrinsic elongation factors are all required for ENL condensate formation. Extensive mutagenesis establishes condensate formation as a driver of oncogenic gene activation. Furthermore, expression of ENL mutants beyond the endogenous level leads to non-functional condensates. Our findings provide new mechanistic and functional insights into cancer-associated condensates and support condensate dysregulation as an oncogenic mechanism.