Identification of the Binding Site between Aptamer sgc8c and PTK7.

Aptamers are single-stranded RNA or DNA molecules that can specifically bind to targets and have found broad applications in cancer early-stage detection, accurate drug delivery, and precise treatment. Although various aptamer screening methods have been developed over the past several decades, the accurate binding site between the target and the aptamer cannot be characterized during a typical aptamer screening process. In this research, we chose a widely used aptamer screened by our group, sgc8c, and its target protein tyrosine kinase 7 (PTK7) as the model aptamer and target and tried to determine the binding site between aptamer sgc8c and PTK7. Through sequential protein truncation, we confirmed that the exact binding site of sgc8c was within the region of Ig 3 to Ig 4 in the extracellular domain of PTK7. Using in vitro expressed Ig (3-4), we successfully acquired the crystal of an sgc8c-Ig (3-4) binding complex. The possible sgc8c-binding amino acid residues on PTK7 and PTK7-binding nucleotide residues on sgc8c were further identified and simulated by mass spectrometry and molecular dynamics simulation and finally verified by aptamer/protein truncation and mutation.

Spatial transcriptomics reveals heterogeneity of macrophages in the tumor microenvironment of granulomatous slack skin.

Granulomatous slack skin (GSS) is an extremely rare subtype of cutaneous T-cell lymphoma accompanied by an abundant number of macrophages and is clinically characterized by the development of pendulous skin folds. However, the characteristics of these macrophages in GSS remain unclear. Here, we conducted a spatial transcriptomic study on one frozen GSS sample and drew transcriptomic maps of GSS for the first time. Gene expression analysis revealed the enrichment of three clusters with macrophage transcripts, each exhibiting distinct characteristics suggesting that their primary composition consists of different subpopulations of macrophages. The CD163+ /CD206+ cluster showed a tumor-associated macrophage (TAM) M2-like phenotype and highly expressed ZFP36, CCL2, TNFAIP6, and KLF2, which are known to be involved in T-cell interaction and tumor progression. The APOC1+ /APOE+ cluster presented a non-M1 or -M2 phenotype and may be related to lipid metabolism. The CD11c+ /LYZ+ cluster exhibited an M1-like phenotype. Notably, these cells strongly expressed MMP9, MMP12, CHI3L1, CHIT1, COL1A1, TIMP1, and SPP1, which are responsible for extracellular matrix (ECM) degradation and tissue remodeling. This may partially explain the symptoms of cutaneous relaxation in GSS. Further immunohistochemistry on four GSS cases demonstrated that CD11c predominantly marked granulomas and multinucleated giant cells, whereas CD163 was mainly expressed on scattered macrophages, appearing as a mutually exclusive pattern. The expression pattern of MMP9 overlapped with that of CD11c, implying that CD11c+ macrophages may be a source of MMP9. Our data shed light on the characteristics of macrophages in the GSS microenvironment and provide a theoretical basis for the application of MMP9 inhibitors to prevent cutaneous relaxation of GSS. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Multi-parameter Inputted Logic-Gating on Aptamer-Encoded Extracellular Vesicles for Colorectal Cancer Diagnosis.

Extracellular vesicles (EVs) have emerged as a potential biomarker in liquid biopsy. However, cancer heterogeneity poses significant challenge to precise molecular diagnosis based on single-parameter input. Hence, strategies for analyzing multiple inputs with molecular computing were developed with the aim of improving diagnostic accuracy in liquid biopsy. In the present study, based on the surface of aptamer-encoded EVs, three toe-hold extended DNA aptamers served as specific inputs to perform AND-logic-gating to distinguish between healthy and cancerous EVs. In addition, this strategy has been successfully employed to analyze circulating EVs in clinical samples from colorectal cancer patients and healthy donors. The developed method has a promising future in the analysis of multiplex EV membrane proteins and the identification of early cancer.

Power Management and Reaction Optimization for a Self-Powered Electrochemical System Driven by a Triboelectric Nanogenerator.

Harvesting distributed and low-quality mechanical energies by triboelectric nanogenerators to power electrochemical reactions is beneficial to electric energy saving and certain applications. However, the conventional self-powered electrochemical process is awkward about the reaction rate, energy conversion efficiency, high-operation frequency, and mismatched impedance. Here we demonstrate an advanced self-powered electrochemical system. In comparison with the conventional system that is inert in activity, the superior power management and electrochemical reaction regulation in tandem make the novel system outstanding for hydrogen peroxide production. In addition to the visible product, an internal current efficiency of 24.6% in the system was achieved. The developed system provides an optimization strategy toward electric energy saving for electrochemical reactions as well as enabling their applications in remote areas by converting environmental mechanical vibrational energy for ecological improvement or recyclable chemical fuel generation.

Diastereoselective synthesis of spiro-cyclopropanyl-cyclohexadienones via direct sulfide-catalyzed [2 + 1] annulation of para-quinone methides with bromides.

An efficient sulfide-catalyzed [2 + 1] annulation of para-quinone methides (p-QMs) with diverse bromides has been achieved. This catalytic strategy provides an efficient and straightforward protocol for accessing a variety of spiro-cyclopropanyl-cyclohexadienone compounds in good to excellent yields (64% to 96% yields) with outstanding diastereoselectivities (>20 : 1 dr), displaying good functional group tolerance as well as gram-scale capacity.

Visible-light induced decarboxylative alkylation of quinoxalin-2(1H)-ones at the C3-position.

A simple and efficient method for the visible light induced direct carbon alkylation of quinoxalin-2(1H)-ones at the C3 position is described. This protocol employs cheap and readily available phenyliodine(iii) dicarboxylates as the alkylation reagents to conduct decarboxylative radical coupling reaction with quinoxalin-2(1H)-ones. The process exhibits excellent compatibility to functional groups and provides a convenient and selective access to various 3-alkylquinoxalin-2(1H)-ones in good yields.

Unveiling the Role of Defects on Oxygen Activation and Photodegradation of Organic Pollutants.

The status of defects of TiO2 are of fundamental importance in determining its physicochemical properties. Here we report a simple chemical deposition method for controllable synthesis of defective anatase TiO2 nanocrystals under various calcination atmospheres. XPS and ESR analysis reveals that both the oxygen vacancies ( VO) and the trivalent titanium (Ti3+) defects exist in TiO2 after N2 treatment (N-TiO2). Meanwhile, mainly VO defects can be obtained in TiO2 with air calcination (A-TiO2). ESR spectra for reactive oxygen species determination, clearly show that the visible light catalytic activity is mainly caused by the efficient activation of oxygen molecules to •O2- species for A-TiO2, which play an important role in hindering the accumulation of intermediates during p-chlorophenol (4-CP) photodegradation process. However, the oxygen molecules cannot be activated for N-TiO2 even with superior visible light absorption and thus the photogenerated electron are reductant, which participated in the transformation of BQ to HQ via electron shuttle mechanism. Moreover, A-TiO2 exhibits higher separation efficiency of photogenerated carriers than that of N-TiO2, showing the critical role of VO with a suitable concentration in transferring photogenerated charges.

Enhanced Photocatalytic Degradation Performance by Fluid-Induced Piezoelectric Field.

The introduction of a piezoelectric field has been proven a promising method to enhance photocatalytic activity by preventing photoelectron-hole recombination. However, the formation of a piezoelectric field requires additional mechanical force or high-frequency ultrasonic baths, which limits its potential application on industrial scale. Therefore, it is of great practical significance to design the catalyst that can harvest the discrete energy such as the fluid mechanical energy to form the electric field. Herein, PZT/TiO2 catalyst with a core-shell configuration was prepared by a simple coating method. By collecting the mechanical energy of water, an internal piezoelectric field was induced. Under 800 rpm stirring, transient photocurrent measured on PZT/TiO2 electrode is about 1.7 times higher than that of 400 rpm. Correspondingly, the photocatalytic degradation rate and mineralization efficiency of RhB, BPA, phenol, p-chlorophenol much improved, showing the promoting effect of piezoelectric field generated directly from harvesting the discrete fluid mechanical energy.

Phytoplankton Functional Groups Variation and Influencing Factors in a Shallow Temperate Lake.

The present study was carried out in Luoma Lake, a shallow lake in temperate eastern China. Based on a two-year study, the dynamics of phytoplankton functional groups and influencing factors were analyzed. A total of 178 taxa were identified and sorted into 20 codons, according to the phytoplankton functional group classification. In order to find the environmental factors driving phytoplankton variations, fifteen groups were analyzed in detail using redundancy analysis. Groups P (Fragilaria crotonensis), X2 (Chlamydomonas globosa, C. microsphaera and Chroomonas acuta), and MP (Navicula rotaeana) were dominant during low temperature periods, whereas groups X2, S1 (Pseudanabaena limnetica), and W1 (Euglena sp.) were dominant during high temperature periods. Water temperature, total phosphorus, and ammonium were the significant driving factors explaining phytoplankton succession. Furthermore, total phosphorus and ammonium could be broadly used in risk management for potential algal blooms in Luoma Lake.

Spatiotemporal distribution pattern of cyanobacteria community and its relationship with the environmental factors in Hongze Lake, China.

Hongze Lake, located in the east route of the South-to-North Water Diversion Project (SNWDP), is a potential drinking water source for the residents along this water diversion project. Based on a monthly sampling at 11 stations in three regions of Hongze Lake, the spatiotemporal distribution pattern of cyanobacteria community was comprehensively investigated from March 2011 to February 2013. A total of 23 cyanobacterial species which belong to 16 genera were identified, and Microcystis was the most predominant cyanobacterial genus mainly composed of Microcystis wesenbergii in Hongze Lake. The cyanobacterial abundance ranged from 0 to 2.6 × 10(7) cells/L, and the average cyanobacteria abundance of Northern region was significantly higher than those of Western region and Eastern region in the 2-year study. The total cyanobacteria abundance and the Microcystis abundance both took on a similar seasonal regularity in the three regions. The results of correlation analysis indicated that Microcystis abundance was correlated with water temperature, chemical oxygen demand (COD)Mn, nitrate (NO3-N), and total nitrogen (TN)/total phosphorus (TP) mass ratio, among which water temperature had the highest correlation coefficient. In summer, cyanobacteria blooms may take place under suitable environmental conditions at some special areas in Hongze Lake, especially where the concurrence of slow water exchange and steady wind direction exists.

[Corrigendum] Propofol­induced HOXA11­AS promotes proliferation, migration and invasion, but inhibits apoptosis in hepatocellular carcinoma cells by targeting miR­4458.

Following the publication of the above article, an interested reader drew to the authors' attention that the western blots for the PCNA and cyclin D1 bands appeared to be strikingly similar. The authors were able to re­examine their original data, and recognize how the error was made with respect to the compilation of this figure (they were also able to demonstrate to the Editorial Office how the error occurred). The revised version of Fig. 3, now incorporating the correct data for the PCNA bands in Fig. 3A, is shown on the next page. The authors can confirm that the errors associated with this figure did not have a significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 46: 1135­1145, 2020; DOI: 10.3892/ijmm.2020.4667].

A contact-electro-catalysis process for producing reactive oxygen species by ball milling of triboelectric materials.

Ball milling is a representative mechanochemical strategy that uses the mechanical agitation-induced effects, defects, or extreme conditions to activate substrates. Here, we demonstrate that ball grinding could bring about contact-electro-catalysis (CEC) by using inert and conventional triboelectric materials. Exemplified by a liquid-assisted-grinding setup involving polytetrafluoroethylene (PTFE), reactive oxygen species (ROS) are produced, despite PTFE being generally considered as catalytically inert. The formation of ROS occurs with various polymers, such as polydimethylsiloxane (PDMS) and polypropylene (PP), and the amount of generated ROS aligns well with the polymers' contact-electrification abilities. It is suggested that mechanical collision not only maximizes the overlap in electron wave functions across the interface, but also excites phonons that provide the energy for electron transition. We expect the utilization of triboelectric materials and their derived CEC could lead to a field of ball milling-assisted mechanochemistry using any universal triboelectric materials under mild conditions.

Enhancing Specific Fluorescence In Situ Hybridization with Quantum Dots for Single-Molecule RNA Imaging in Formalin-Fixed Paraffin-Embedded Tumor Tissues.

Single-molecule fluorescence in situ hybridization (smFISH) represents a promising approach for the quantitative analysis of nucleic acid biomarkers in clinical tissue samples. However, low signal intensity and high background noise are complications that arise from diagnostic pathology when performed with smFISH-based RNA imaging in formalin-fixed paraffin-embedded (FFPE) tissue specimens. Moreover, the associated complex procedures can produce uncertain results and poor image quality. Herein, by combining the high specificity of split DNA probes with the high signal readout of ZnCdSe/ZnS quantum dot (QD) labeling, we introduce QD split-FISH, a high-brightness smFISH technology, to quantify the expression of mRNA in both cell lines and clinical FFPE tissue samples of breast cancer and lung squamous carcinoma. Owing to its high signal-to-noise ratio, QD split-FISH is a fast, inexpensive, and sensitive method for quantifying mRNA expression in FFPE tumor tissues, making it suitable for biomarker imaging and diagnostic pathology.

Recent advances in genetic etiology of non-syndromic deafness in children.

Congenital auditory impairment is a prevalent anomaly observed in approximately 2-3 per 1,000 infants. The consequences associated with hearing loss among children encompass the decline of verbal communication, linguistic skills, educational progress, social integration, cognitive aptitude, and overall well-being. Approaches to reversing or preventing genetic hearing loss are limited. Patients with mild and moderate hearing loss can only use hearing aids, while those with severe hearing loss can only acquire speech and language through cochlear implants. Both environmental and genetic factors contribute to the occurrence of congenital hearing loss, and advancements in our understanding of the pathophysiology and molecular mechanisms underlying hearing loss, coupled with recent progress in genetic testing techniques, will facilitate the development of innovative approaches for treatment and screening. In this paper, the latest research progress in genetic etiology of non-syndromic deafness in children with the highest incidence is summarized in order to provide help for personalized diagnosis and treatment of deafness in children.

Serum levels of angiotensin-converting enzyme 2 in children with Kawasaki disease.

Kawasaki disease (KD) has replaced rheumatic fever as the main cause of acquired heart disease in Japanese, American, and Chinese children. Polymorphisms in angiotensin-converting enzyme may be associated with susceptibility to KD, but the association of angiotensin-converting enzyme 2 (ACE2) with vascular endothelial injury in KD and the possibility for prognosis of vascular injury in KD by evaluating changes in serum ACE2 have not yet been assessed. Thus, this study aimed to investigate ACE2 levels in patients with KD to further explore the relationship between ACE2 and vascular injury in KD. Blood samples were collected from 49 children with KD before intravenous immunoglobulin treatment and 28 healthy children in the same period as the control group. Clinical data were collected from the patients and serum ACE2 levels of all participants were measured using an enzyme-linked immunosorbent assay. Serum ACE2 levels were significantly higher in the KD group than in the control group, and were negatively correlated with platelet levels in patients with KD. Serum ACE2 levels are related to the pathogenesis of KD and may be used as a potential serum marker for KD diagnosis.

Development and validation of a practical machine learning model to predict sepsis after liver transplantation.

BACKGROUND: Postoperative sepsis is one of the main causes of mortality after liver transplantation (LT). Our study aimed to develop and validate a predictive model for postoperative sepsis within 7 d in LT recipients using machine learning (ML) technology. METHODS: Data of 786 patients received LT from January 2015 to January 2020 was retrospectively extracted from the big data platform of Third Affiliated Hospital of Sun Yat-sen University. Seven ML models were developed to predict postoperative sepsis. The area under the receiver-operating curve (AUC), sensitivity, specificity, accuracy, and f1-score were evaluated as the model performances. The model with the best performance was validated in an independent dataset involving 118 adult LT cases from February 2020 to April 2021. The postoperative sepsis-associated outcomes were also explored in the study. RESULTS: After excluding 109 patients according to the exclusion criteria, 677 patients underwent LT were finally included in the analysis. Among them, 216 (31.9%) were diagnosed with sepsis after LT, which were related to more perioperative complications, increased postoperative hospital stay and mortality after LT (all p < .05). Our results revealed that a larger volume of red blood cell infusion, ascitic removal, blood loss and gastric drainage, less volume of crystalloid infusion and urine, longer anesthesia time, higher level of preoperative TBIL were the top 8 important variables contributing to the prediction of post-LT sepsis. The Random Forest Classifier (RF) model showed the best overall performance to predict sepsis after LT among the seven ML models developed in the study, with an AUC of 0.731, an accuracy of 71.6%, the sensitivity of 62.1%, and specificity of 76.1% in the internal validation set, and a comparable AUC of 0.755 in the external validation set. CONCLUSIONS: Our study enrolled eight pre- and intra-operative variables to develop an RF-based predictive model of post-LT sepsis to assist clinical decision-making procedure.

Postoperative sepsis is one of the main causes of mortality after liver transplantation (LT).Our results revealed that a larger volume of red blood cell infusion, ascitic removal, blood loss and gastric drainage, less volume of crystalloid infusion and urine, longer anesthesia time, higher level of preoperative TBIL were the top 8 important variables contributing to the prediction of post-LT sepsis.The Random Forest Classifier (RF) model showed the best overall performance to predict sepsis after LT in our study, which could assist in the clinical decision-making procedure.

Achieving Extreme Pressure Resistance to Liquids on a Super-Omniphobic Surface with Armored Reentrants.

Static repellency and pressure resistance to liquids are essential for high-performance super-omniphobic surfaces. However, these two merits appear mutually exclusive in conventional designs because of their conflicting structural demands: Static liquid repellency necessitates minimal solid-liquid contact, which in turn inevitably undercuts the surface's ability to resist liquid invasion exerted by the elevated pressure. Here, inspired by the Springtail, these two merits can be simultaneously realized by structuring surfaces at two size scales, with a micrometric reentrant structure providing static liquid repellency and a nanometric reentrant structure providing pressure resistance, which dexterously avoids the dilemma of their structural conflicts. The nanometric reentrants are densely packed on the micrometric ones, serving as "armor" that prevents liquids invasion by generating multilevel energy barriers, thus naming the surface as the armored reentrants (AR) surface. The AR surface could repel liquids with very low surface tensions, such as silicone oil (21 mN m-1 ), and simultaneously resist great pressure from the liquids, exemplified by enduring the impact of low-surface-tension liquids under a high weber number (>400), the highest-pressure resistance ever reported. With its scalable fabrication and enhanced performance, our design could extend the application scope of liquid-repellent surfaces toward ultimate industrial settings.

Enhanced degradation of amiloride over Bi2FeNbO7/bisulfite process: Key factors and mechanism.

Construction of Bi2FeNbO7/bisulfite system for abatement of pharmaceutical residue was achieved. An attempt to synthesize Bi2FeNbO7 through hydrothermal technique was confirmed by X-ray diffraction. The magnetic field experiment revealed that Bi2FeNbO7 possessed a saturation magnetization of 6.99 emu/g, indicating magnetic attributes of Bi2FeNbO7. Scanning electron microscopy images showed that Bi2FeNbO7 exhibited regular octahedra in the size of 200-300 nm. In a self-made device, the activation of sodium bisulfite using Bi2FeNbO7 for the disposal of amiloride has been carefully explored. The effects of solution pH, sodium bisulfite concentration, Bi2FeNbO7 dosage, amiloride concentration, coexisting ions, and water matrix on the performance of Bi2FeNbO7/bisulfite system was investigated. The catalytic performance of Bi2FeNbO7/bisulfite to degrade amiloride was considerably higher than that of traditional iron oxides. The maximum removal efficiency of amiloride was 97.9% in Bi2FeNbO7/bisulfite process. The involvement of Fe might be crucial for activating bisulfite to create active species. The dominating radical in Bi2FeNbO7/bisulfite process was identified as SO3•‒. With the help of UHPLC/MS/MS, three new degradation products of amiloride were found. Dehalogenation and deamination of amiloride might account for the formation of these transformation products. This work provides a highly efficient Bi2FeNbO7/bisulfite process for the disposal of pharmaceutical pollutants in water treatment.

The Role of TAMs in Tumor Microenvironment and New Research Progress.

Tumor-associated macrophages (TAMs) are an important part of tumor microenvironment (TME) and play a key role in TME, participating in the process of tumor occurrence, growth, invasion, and metastasis. Among them, metastasis to tumor tissue is the key step of malignant development of tumor. In this paper, the latest progress in the role of TAMs in the formation of tumor microenvironment is summarized. It is particularly noteworthy that cell and animal experiments show that TAMs can provide a favorable microenvironment for the occurrence and development of tumors. At the same time, clinical pathological experiments show that the accumulation of TAMs in tumor is related to poor clinical efficacy. Finally, this paper discusses the feasibility of TAMs-targeted therapy as a new indirect cancer therapy. This paper provides a theoretical basis for finding a potentially effective macrophage-targeted tumor therapy.

Contact-electro-catalysis for the degradation of organic pollutants using pristine dielectric powders.

Mechanochemistry has been studied for some time, but research on the reactivity of charges exchanged by contact-electrification (CE) during mechanical stimulation remains scarce. Here, we demonstrate that electrons transferred during the CE between pristine dielectric powders and water can be utilized to directly catalyze reactions without the use of conventional catalysts. Specifically, frequent CE at Fluorinated Ethylene Propylene (FEP) - water interface induces electron-exchanges, thus forming reactive oxygen species for the degradation of an aqueous methyl orange solution. Contact-electro-catalysis, by conjunction of CE, mechanochemistry and catalysis, has been proposed as a general mechanism, which has been demonstrated to be effective for various dielectric materials, such as Teflon, Nylon-6,6 and rubber. This original catalytic principle not only expands the range of catalytic materials, but also enables us to envisage catalytic processes through mechano-induced contact-electrification.