Fluorogenic Peptide Sensor Array Derived from Angiotensin-Converting Enzyme 2 Classifies Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern.

The devastating COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made society acutely aware of the urgency in developing effective techniques to timely monitor the outbreak of previously unknown viral species as well as their mutants, which could be even more lethal and/or contagious. Here, we report a fluorogenic sensor array consisting of peptides truncated from the binding domain of human angiotensin-converting enzyme 2 (hACE2) for SARS-CoV-2. A set of five fluorescently tagged peptides were used to construct the senor array in the presence of different low-dimensional quenching materials. When orthogonally incubated with the wild-type SARS-CoV-2 and its variants of concern (VOCs), the fluorescence of each peptide probe was specifically recovered, and the different recovery rates provide a "fingerprint" characteristic of each viral strain. This, in turn, allows them to be differentiated from each other using principal component analysis. Interestingly, the classification result from our sensor array agrees well with the evolutionary relationship similarity of the VOCs. This study offers insight into the development of effective sensing tools for highly contagious viruses and their mutants based on rationally truncating peptide ligands from human receptors.

Metal-organic cages for gas adsorption and separation.

The unique high surface area and tunable cavity size endow metal-organic cages (MOCs) with superior performance and broad application in gas adsorption and separation. Over the past three decades, for instance, numerous MOCs have been widely explored in adsorbing diverse types of gas including energy gases, greenhouse gases, toxic gases, noble gases, etc. To gain a better understanding of the structure-performance relationships, great endeavors have been devoted to ligand design, metal node regulation, active metal site construction, cavity size adjustment, and function-oriented ligand modification, thus opening up routes toward rationally designed MOCs with enhanced capabilities. Focusing on the unveiled structure-performance relationships of MOCs towards target gas molecules, this review consists of two parts, gas adsorption and gas separation, which are discussed separately. Each part discusses the cage assembly process, gas adsorption strategies, host-guest chemistry, and adsorption properties. Finally, we briefly overviewed the challenges and future directions in the rational development of MOC-based sorbents for application in challenging gas adsorption and separation, including the development of high adsorption capacity MOCs oriented by adsorbability and the development of highly selective adsorption MOCs oriented by separation performance.

Orthogonally Engineered Albumin with Attenuated Macrophage Phagocytosis for the Targeted Visualization and Phototherapy of Liver Cancer.

The five-year survival rate of hepatocellular carcinoma (HCC) remains unsatisfactory. This reflects, in part, the paucity of effective methods that allow the target-specific diagnosis and therapy of HCC. Here, we report a strategy based on engineered human serum albumin (HSA) that permits the HCC-targeted delivery of diagnostic and therapeutic agents. Covalent cysteine conjugation combined with the exploitation of host-guest chemistry was used to effect the orthogonal functionalization of HSA with two functionally independent peptides. One of these peptides targets glypican-3 (GPC-3), an HCC-specific biomarker, while the second reduces macrophage phagocytosis through immune-checkpoint stimulation. This orthogonally engineered HSA proved effective for the GPC-3-targeted delivery of near-infrared fluorescent and phototherapeutic agents, thus permitting target-specific optical visualization and photodynamic ablation of HCC in vivo. This study thus offers new insights into specificity-enhanced fluorescence-guided surgery and phototherapy of HCC through the orthogonal engineering of biocompatible proteins.

Risk prediction of intraoperative pain in percutaneous microwave ablation of lung tumors under CT guidance.

OBJECTIVES: To evaluate the effect of intraoperative pain in microwave ablation of lung tumors (MWALT) on local efficacy and establish the pain risk prediction model. METHODS: It was a retrospectively study. Consecutive patients with MWALT from September 2017 to December 2020 were divided into mild and severe pain groups. Local efficacy was evaluated by comparing technical success, technical effectiveness, and local progression-free survival (LPFS) in two groups. All cases were randomly allocated into training and validation cohorts at a ratio of 7:3. A nomogram model was established using predictors identified by logistics regression in training dataset. The calibration curves, C-statistic, and decision curve analysis (DCA) were used to evaluate the accuracy, ability, and clinical value of the nomogram. RESULTS: A total of 263 patients (mild pain group: n = 126; severe pain group: n = 137) were included in the study. Technical success rate and technical effectiveness rate were 100% and 99.2% in the mild pain group and 98.5% and 97.8% in the severe pain group. LPFS rates at 12 and 24 months were 97.6% and 87.6% in the mild pain group and 91.9% and 79.3% in the severe pain group (p = 0.034; HR: 1.90). The nomogram was established based on three predictors: depth of nodule, puncture depth, and multi-antenna. The prediction ability and accuracy were verified by C-statistic and calibration curve. DCA curve suggested the proposed prediction model was clinically useful. CONCLUSIONS: Severe intraoperative pain in MWALT reduced the local efficacy. An established prediction model could accurately predict severe pain and assist physicians in choosing a suitable anesthesia type. CLINICAL RELEVANCE STATEMENT: This study firstly provides a prediction model for the risk of severe intraoperative pain in MWALT. Physicians can choose a suitable anesthesia type based on pain risk, in order to improve patients' tolerance as well as local efficacy of MWALT. KEY POINTS: • The severe intraoperative pain in MWALT reduced the local efficacy. • Predictors of severe intraoperative pain in MWALT were the depth of nodule, puncture depth, and multi-antenna. • The prediction model established in this study can accurately predict the risk of severe pain in MWALT and assist physicians in choosing a suitable anesthesia type.

Fluorescence Analysis of Circulating Exosomes for Breast Cancer Diagnosis Using a Sensor Array and Deep Learning.

Emerging liquid biopsy methods for investigating biomarkers in bodily fluids such as blood, saliva, or urine can be used to perform noninvasive cancer detection. However, the complexity and heterogeneity of exosomes require improved methods to achieve the desired sensitivity and accuracy. Herein, we report our study on developing a breast cancer liquid biopsy system, including a fluorescence sensor array and deep learning (DL) tool AggMapNet. In particular, we used a 12-unit sensor array composed of conjugated polyelectrolytes, fluorophore-labeled peptides, and monosaccharides or glycans to collect fluorescence signals from cells and exosomes. Linear discriminant analysis (LDA) processed the fluorescence spectral data of cells and cell-derived exosomes, demonstrating successful discrimination between normal and different cancerous cells and 100% accurate classification of different BC cells. For heterogeneous plasma-derived exosome analysis, CNN-based DL tool AggMapNet was applied to transform the unordered fluorescence spectra into feature maps (Fmaps), which gave a straightforward visual demonstration of the difference between healthy donors and BC patients with 100% prediction accuracy. Our work indicates that our fluorescent sensor array and DL model can be used as a promising noninvasive method for BC diagnosis.

Graphene nanoribbon-based supramolecular ensembles with dual-receptor targeting function for targeted photothermal tumor therapy.

Triple negative breast cancer (TNBC) is one of the most malignant subtypes of breast cancer. Here, we report the construction of graphene nanoribbon (GNR)-based supramolecular ensembles with dual-receptor (mannose and αvß3 integrin receptors) targeting function, denoted as GNR-Man/PRGD, for targeted photothermal treatment (PTT) of TNBC. The GNR-Man/PRGD ensembles were constructed through the solution-based self-assembly of mannose-grafted GNRs (GNR-Man) with a pyrene-tagged αvß3 integrin ligand (PRGD). Enhanced PTT efficacies were achieved both in vitro and in vivo compared to that of the non-targeting equivalents. Tumor-bearing live mice were administered (tail vein) with GNR-Man/PRGD and then each mice group was subjected to PTT. Remarkably, GNR-Man/PRGD induced complete ablation of the solid tumors, and no tumor regrowth was observed over a period of 15 days. This study demonstrates a new and promising platform for the development of photothermal nanomaterials for targeted tumor therapy.

Preoperative computed tomographic-guided percutaneous coil localization of pulmonary nodules: 184 Cases in Single-center.

OBJECTIVES: The aim of this study was to evaluate the feasibility, accuracy, and safety of computed tomographic (CT)-guided coil localization before video-assisted thoracoscopic surgery. METHODS: One hundred and eighty-four consecutive patients with 200 pulmonary nodules who underwent CT-guided percutaneous coil localization before thoracoscopic surgery were retrospectively analyzed in this study. Success rate for localization, complication rates, CT findings, and pathological results of the lesions, as well as the data related to surgery were all recorded and analyzed. RESULTS: All 184 patients with 200 lesions completed localization and resection. The success rate of the coil localization on lesion baseline was 99.0% (198/200) and 98.9% (182/184) on patient baseline. The number of wedge resection, segmental resection, and lobectomy were 179 (89.5%), 19 (9.5%), and 2 (1.0%), respectively. The malignancy rates in a lesion-based analysis were 83.5% (91.1% in ground-glass nodules, 91.4% in part-solid nodules, and 37.9% in solid nodules). No serious complications occurred in all localization procedures. CONCLUSION: Preoperative CT-guided percutaneous coil localization is a safe and effective method to facilitate high success rates for both wedge and segmental resection for peripheral pulmonary nodules.

Clinical effect of bronchial arterial infusion chemotherapy and CalliSpheres drug-eluting beads in patients with stage II-IV lung cancer: A prospective cohort study.

BACKGROUND: CalliSpheres are drug-eluting beads used for tumor artery embolization, with clinical benefits in a number of cancer types. The aim of the study was to examine the clinical benefits and complications of patients with stage II-IV lung cancer treated with CalliSpheres drug-eluting beads for embolization versus conventional vascular interventional treatment. METHODS: This was a prospective cohort study conducted from August 2018 to May 2019. The patients were grouped according to traditional bronchial arterial infusion chemotherapy (infusion group) or bronchial arterial chemoembolization with CalliSpheres drug-eluting beads loaded with adriamycin (CallisSphere group). Short-term effects, serum tumor markers, and adverse reactions during follow-up were compared between the two groups. RESULTS: There were 60 participants enrolled into the study with 30 in each group including 54 men and six women, 42-78 years of age. In the CalliSphere group, compared with the infusion group, the disease control rate was 93.3% versus 73.3% (P = 0.080) and the objective remission rate (ORR) was 86.7% versus 60.0% (P = 0.039); the three- and six-month progression-free survival (PFS) and six-month overall survival (OS) were better in the CalliSphere group (three-month PFS: 96.7% vs. 73.3%, P = 0.026; six-month PFS: 87.5% vs. 57.1%, P = 0.045; six-month OS: 87.5% vs. 52.7%, P = 0.024); after treatment, the tumor markers in the CalliSphere group were lower (CEA: P < 0.001; CYFRA21-1: P = 0.014). There were no differences in adverse reactions between the two groups. CONCLUSIONS: The clinical effect of bronchial arterial chemoembolization with drug-eluting beads on lung cancer is probably significant and could improve the short-term response, PFS, and OS in patients with stage IIIV lung cancer, without increasing severe adverse reactions. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: The clinical effect of bronchial arterial chemoembolization with drug-eluting beads on lung cancer is probably significant and could improve the short-term response, PFS, and OS in patients with stage II-IV lung cancer, without increasing severe adverse reactions. WHAT THIS STUDY ADDS: The ORR, PFS, OS was better in the CalliSphere group than that of infusion group; CEA and CYFRA21-1 were significant lower in CalliSphere group.

Supramolecular fluorogenic peptide sensor array based on graphene oxide for the differential sensing of ebola virus.

We report on a supramolecular sensor array using fluorogenic peptide probes and graphene oxide that can target glycoproteins on a viral caspid, facilitating the differentiation of ebola virus from marburg virus and receptor-extensive vesicular stomatitis virus using principal component analysis.

Correction: Fluorescence imaging of a potential diagnostic biomarker for breast cancer cells using a peptide-functionalized fluorogenic 2D material.

Correction for 'Fluorescence imaging of a potential diagnostic biomarker for breast cancer cells using a peptide-functionalized fluorogenic 2D material' by Wei-Tao Dou et al., Chem. Commun., 2019, 55, 13235-13238.

Fluorescence imaging of a potential diagnostic biomarker for breast cancer cells using a peptide-functionalized fluorogenic 2D material.

Protein C receptor (PROCR) is a recently discovered transmembrane biomarker for several tissue stem cells and is highly expressed in triple-negative breast cancer (TNBC) patient-derived xenografts. Herein, to enrich the toolbox for the biochemical evaluation of PROCR, we have developed a peptide-functionalized fluorogenic 2D material based on the self-assembly between a fluorescent peptide probe and thin-layer molybdenum disulfide. The material developed was suitable for the sensitive detection of PROCR recombinant protein in buffer solution and the fluorescence imaging of TNBC cells that express high levels of PROCR.

Conjugated polyelectrolytes with galactose-containing side chains for targeted hepatoma cell imaging.

Three cationic conjugated polyelectrolytes (CPEs) with a common poly(p-phenylene ethynylene) backbone and different galactose-containing side chains were designed and synthesized. These CPEs were characterized and their application in targeted hepatoma cell imaging was demonstrated.

Fluorogenic 2D Peptidosheet Unravels CD47 as a Potential Biomarker for Profiling Hepatocellular Carcinoma and Cholangiocarcinoma Tissues.

A 2D peptidosheet unravels CD47 as a potential biomarker to image hepatocarcinoma and cholangiocarcinoma cells and tissues. Supramolecular assembly between water-soluble 2D MoS2 and a peptide probe produces the 2D peptidosheet suited for the profiling of hepatocarcinoma and cholangiocarcinoma tissues over healthy tissues on clinical specimens.

Interlocked supramolecular glycoconjugated polymers for receptor-targeting theranostics.

We report an interlocked supramolecular ensemble formed between a conjugated polymer (CP) and a fluorescent glycoprobe for receptor-targeting cancer cell theranostics.