Rapid detection of hypobromous acid by a tetraphenylethylene-based turn-on fluorescent AIE probe and its applications.

BACKGROUND: Similar to hypochlorous acid (HClO), hypobromous acid (HBrO) is one of the most notable reactive oxygen species (ROS). Overexpression of HBrO is linked to various diseases causing organ and tissue loss. Due to HBrO's role in the oxidation of micropollutants, real-time monitoring of HBrO in water-based systems is essential. Tetraphenylethylene (TPE)-based organic aggregation-induced emission luminophores (AIEgens) are an emerging category of fluorescent probe materials that have attracted considerable attentions. However, AIE probes are rarely applied to detect HBrO. Developing faster, more precise, and more sensitive AIE probes is thus crucial for detecting biological and environmental HBrO. RESULTS: A small molecule fluorescent probe 4-(1,2,2-triphenylvinyl)benzamidoxime (SWJT-21) was synthesized for the sensitive and selective detection of hypobromous acid (HBrO) based on aggregation-induced emission (AIE). The amidoxime unit of SWJT-21 would undergo an oxidation reaction with HBrO, leading to a structure differentiation between the probe and the product, and therefore the turn-on fluorescence by the AIE effect. The probe could recognize hypobromous acid rapidly (less than 3 s) in high aqueous phase (99 % water) with a turn-on fluorescence response. It was determined that the limit of detection for HBrO was 5.47 nM. Moreover, SWJT-21 demonstrates potential as a test strip for the detection of HBrO. SWJT-21 was also successfully used for the monitoring of HBrO in water samples and for the detection of endogenous/exogenous HBrO in living cells and zebrafish. SIGNIFICANCE: A special AIE fluorescence turn-on probe SWJT-21 based on tetraphenylethylene was designed for detecting HBrO in the environmental and biological systems. This probe has an extremely low detection limit of 5.47 nM and is able to detect HBrO in 99 % aqueous phase in less than 3 s.

An electromechanical stimulation regulating model with flexoelectric effect of piezoelectric laminated micro-beam for cell bionic culture.

Cell bionic culture requires the construction of cell growth microenvironments. In this paper, mechanical force and electrical stimulations are applied to the cells cultured on the surface of the piezoelectric laminated micro-beam driven by an excitation voltage. Based on the extended dielectric theory, the electromechanical microenvironment regulating model of the current piezoelectric laminated micro-beam is established. The variational principle is used to obtain the governing equations and boundary conditions. The differential quadrature method and the iterative method are used to solve two boundary value problems for cantilever beams and simply supported beams. In two cases, the mechanical force and electrical stimulations applied to the cells are analyzed in detail and the microscale effect is investigated. This study is meaningful for improving the quality of cell culture and promoting the cross-integration of mechanics and biomedicine.

Photocatalytic Tandem Radical Cyclization Enables Expeditious Total Synthesis of Epoxyhinokiol Analogues for Anticancer Activity Evaluation.

A photocatalytic radical cascade with an unusual endo-trig cyclization was developed, which enables the efficient assembly of divergent tricyclic diterpenoid frameworks. The first total synthesis of abietane 10-epi-epoxyhinoliol was thus achieved in six steps by a subsequent reductive coupling of i-PrBr under photoredox/nickel dual catalysis. Inhibitory tests of chiral 10-epi-epoxyhinoliol and its analogues in 4T1 cancer cells demonstrated the critical role of the C12 hydroxyl group, leading to a discovery of the simplified analogue with better activity.

Fast detection of hypobromous acid in cells and the water environment using a lysosome-targeted fluorescent probe.

A new fluorescent probe SWJT-23 with lysosomal targeting ability for detection of hypobromous acid (HBrO) was synthesised based on the naphthalimide skeleton. This probe exhibited a fast response (within 3s), a low detection limit (1.24 nM), excellent selectivity and a high fluorescence quantum yield (Φ = 0.490). Moreover, SWJT-23 not only realized the sensitive detection of HBrO in cells and water samples, but also was fabricated as a paper-based sensor. In consequence, SWJT-23 is expected to be an efficient and powerful tool for monitoring HBrO in organisms and the environment in realistic scenarios.

Interactions between circRNA and protein in breast cancer.

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA that plays important roles in the occurrence and development of various cancers. Current research indicates that circRNA can inhibit the function of miRNA by acting as an miRNA sponge, interacting with proteins, and being translated into proteins. Most current research focuses on the circRNA-miRNA interaction; however, few studies have investigated the interaction between circRNAs and RNA binding proteins (RBPs) in breast cancer. In this review, we systematically summarize the potential molecular mechanism of the circRNA-protein interaction in breast cancer. Specifically, we elaborate on the direct interaction between circRNAs and proteins in breast cancer, including the functions of circRNA as protein sponges, decoys, and scaffolds, thereby affecting the progression of breast cancer. We also discuss the indirect interaction between circRNAs and proteins in breast cancer in which RBPs, transcription factors and m6A modifying enzymes could in turn regulate the expression and formation of circRNA. Finally, we discuss the potential application of circRNA-protein interaction for treating breast cancer, providing a reference for further research in this field.

PIN1P1 is activated by CREB1 and promotes gastric cancer progression via interacting with YBX1 and upregulating PIN1.

Long noncoding RNAs (lncRNAs) play critical roles in the carcinogenesis and progression of cancers. However, the role and mechanism of the pseudogene lncRNA PIN1P1 in gastric carcinoma remain unclear. The expression and effects of lncRNA PIN1P1 in gastric cancer were investigated. The transcriptional regulation of CREB1 on PIN1P1 was determined by ChIP and luciferase assays. The mechanistic model of PIN1P1 in gastric cancer was further explored by RNA pull-down, RIP and western blot analysis. PIN1P1 was overexpressed in gastric cancer tissues, and upregulated PIN1P1 predicted poor prognosis in patients. CREB1 was directly combined with the promoter region of PIN1P1 to promote the transcription of PIN1P1. CREB1-mediated enhanced proliferation, migration and invasion could be partially reversed by downregulation of PIN1P1. Overexpressed PIN1P1 promoted the proliferation, migration and invasion of gastric cancer cells, whereas decreased PIN1P1 showed the opposite effects. PIN1P1 directly interacted with YBX1 and promoted YBX1 protein expression, leading to upregulation of PIN1, in which E2F1 may be involved. Silencing of YBX1 during PIN1P1 overexpression could partially rescue PIN1 upregulation. PIN1, the parental gene of PIN1P1, was elevated in gastric cancer tissues, and its upregulation was correlated with poor patient outcomes. PIN1 facilitated gastric cancer cell proliferation, migration and invasion. To sum up, CREB1-activated PIN1P1 could promote gastric cancer progression through YBX1 and upregulating PIN1, suggesting that it is a potential target for gastric cancer.

Intramolecular Ni-catalyzed reductive coupling enables enantiodivergent synthesis of linoxepin.

A nickel-catalyzed reductive tandem cyclization of the elaborated ß-bromo acetal with a dibenzoxepin scaffold was invented to strategically construct the remaining two rings in linoxepin. The generated diasterodivergent intermediates could be easily converted to both enantiomers of this unique cyclolignan molecule via facile oxidations, thus realizing enantiodivergent total synthesis of linoxepin for the first time.

Development of machine learning prognostic models for overall survival of prostate cancer patients with lymph node-positive.

Prostate cancer (PCa) patients with lymph node involvement (LNI) constitute a single-risk group with varied prognoses. Existing studies on this group have focused solely on those who underwent prostatectomy (RP), using statistical models to predict prognosis. This study aimed to develop an easily accessible individual survival prediction tool based on multiple machine learning (ML) algorithms to predict survival probability for PCa patients with LNI. A total of 3280 PCa patients with LNI were identified from the Surveillance, Epidemiology, and End Results (SEER) database, covering the years 2000-2019. The primary endpoint was overall survival (OS). Gradient Boosting Survival Analysis (GBSA), Random Survival Forest (RSF), and Extra Survival Trees (EST) were used to develop prognosis models, which were compared to Cox regression. Discrimination was evaluated using the time-dependent areas under the receiver operating characteristic curve (time-dependent AUC) and the concordance index (c-index). Calibration was assessed using the time-dependent Brier score (time-dependent BS) and the integrated Brier score (IBS). Moreover, the beeswarm summary plot in SHAP (SHapley Additive exPlanations) was used to display the contribution of variables to the results. The 3280 patients were randomly split into a training cohort (n = 2624) and a validation cohort (n = 656). Nine variables including age at diagnosis, race, marital status, clinical T stage, prostate-specific antigen (PSA) level at diagnosis, Gleason Score (GS), number of positive lymph nodes, radical prostatectomy (RP), and radiotherapy (RT) were used to develop models. The mean time-dependent AUC for GBSA, RSF, and EST was 0.782 (95% confidence interval [CI] 0.779-0.783), 0.779 (95% CI 0.776-0.780), and 0.781 (95% CI 0.778-0.782), respectively, which were higher than the Cox regression model of 0.770 (95% CI 0.769-0.773). Additionally, all models demonstrated almost similar calibration, with low IBS. A web-based prediction tool was developed using the best-performing GBSA, which is accessible at https://pengzihexjtu-pca-n1.streamlit.app/ . ML algorithms showed better performance compared with Cox regression and we developed a web-based tool, which may help to guide patient treatment and follow-up.

Sequential detection of inflammation-related hypochlorite ions and viscosity with a relay fluorescent probe.

Based on the correlation between inflammation and reactive oxygen species and viscosity, a fluorescent probe (SWJT-19) was designed for a relay detection of hypochlorite ions and viscosity. The synthesized probe could quickly and selectively detect hypochlorite ions, as well as viscosity of the system effectively. Moreover, the probe had been successfully applied to sequentially detect hypochlorite ions and viscosity in organisms, as well as imaging in mouse inflammation.

An angiogenesis-related lncRNA signature predicts the immune microenvironment and prognosis of breast cancer.

Both angiogenesis and lncRNAs play crucial roles in the development and progression of breast cancer. Considering the unknown association of angiogenesis and lncRNAs in breast cancer, we aim to identify angiogenesis-related lncRNAs (ARLs) and explore their prognostic value. Here, based on analysis of The Cancer Genome Atlas database, the correlation between ARL and the prognosis and immune infiltration landscape of breast cancer were investigated. Eight ARLs (MAFG-DT, AC097478.1, AL357054.4, AL118556.1, SNHG10, MED14OS, OTUD6B-AS1, and CYTOR) were selected to construct the risk model as a prognostic signature. The survival rate of the patients in the high-risk group was lower than that in the low-risk group. The ARL signature was an independent prognostic predictor, and areas under the curve of 1-, 3-, and 5-year survival were 0.745, 0.695, and 0.699, respectively. The prognostic ARLs were associated with the immune infiltration landscape and could indicate the immune status, immune response, tumor mutational burden, and drug sensitivity of patients with breast cancer. Furthermore, qRT-PCR of clinical samples revealed that OTUD6B-AS1 was correlated with prognostic pathological parameters. OTUD6B-AS1 promoted breast cancer cell proliferation, wound healing, migration, invasion, and human umbilical vein endothelial cells tube formation. Mechanistically, OTUD6B-AS1 regulated EMT- and angiogenesis-related molecules. Taken together, we constructed and verified a robust signature of eight ARLs for the prediction of survival in patients with breast cancer, and the characterization of the immune infiltration landscape. Our findings suggest that OTUD6B-AS1 could be a therapeutic target for patients with breast cancer.

A Near-Infrared Colorimetric Fluorescent Probe for Ferrous Ion Detection and Imaging.

Based on the N-redox mechanism, a turn-on near-infrared fluorescence probe (SWJT-15) with cyano isophorone as skeleton was designed and synthesized for the detection of ferrous ions (Fe2+). The probe has a lower detection limit (83 nM) and fast response (200 s) to Fe2+ ions. And the probe has unique selectivity and good anti-interference performance against Fe2+ ions compared to other metal ions. Moreover, the probe has been successfully applied to imaging Fe2+ ions in HeLa cells.

A lysosome-targetable fluorescent probe for the ratiometric detection of formaldehyde in living cells and in vivo.

Inspired by the synthetic method of benzoxazine derivatives and our previous research, a fluorescent probe (SWJT-6) was designed for formaldehyde (FA) detection based on the cyclization reaction. The synthetic SWJT-6 showed excellent colorimetric and ratiometric response to formaldehyde, and could be perfectly used as test strips to detect formaldehyde. It also showed a fast detection time (3 min), low detection limit (5.65 µM) and high selectivity for formaldehyde within various interfering analytes. In addition, SWJT-6 has been successfully applied in bioimaging of intracellular and lysosomal formaldehyde in both HeLa cells and zebrafish.

Breast cancer nipple discharge exosomal microRNAs are stable under degradative conditions.

We have previously shown that microRNAs (miRNAs) in nipple discharge are potential diagnostic biomarkers. In particular, exosomes are present in nipple discharge. Herein, we sought to elucidate the protective role of exosomes on miRNAs in nipple discharge and investigate the stability of miRNAs encapsulated in exosomes under degradative conditions. A novel TTMAAlPc-RNA complex method was used to measure the RNase concentration in colostrum and nipple discharge. Quantitative real-time polymerase chain reaction was performed to test the stability of exogenous synthetic miRNAs (cel-lin-4-5p and cel-miR-2-3p) and endogenous miRNAs (hsa-miR-4732-5p, hsa-miR-3646, hsa-miR-4484, and kshv-miR-K12-5-5p). RNase was present and functional in colostrum and nipple discharge. Endogenous miRNAs were more stably expressed compared to exogenous miRNAs at room temperature and 4°C. Triton X-100 (1%, 30 min) destroyed the exosomal membrane, causing RNA degradation in colostrum but not in nipple discharge. Therefore, we confirmed that exosomes in colostrum and nipple discharge could protect miRNAs from degradation by RNase. Exosomes in nipple discharge may be more resistant to Triton X-100 lysis compared to those in the colostrum. Exosomal miRNAs in nipple discharge in breast cancer are stable under degradative conditions. Differential Triton X-100 sensitivity of exosomes of nipple discharge and colostrum warrants further investigation.

A highly sensitive and selective fluorescent probe for rapid detection and intracellular imaging of Pd(II).

A novel near-infrared fluorescent probe (SWJT-13) for detecting Pd2+ ions was designed and synthesized using 3-bromopropargyne group as a recognition site. SWJT-13 can detect Pd2+ ions specifically, which can be quickly recognized by naked eye under natural light. SWJT-13 has a large Stokes shift (155 nm) with LOD of 10.5 nM. The mechanism was verified by 1H NMR, MS, and Gaussian calculations. In addition, the detection of Pd2+ ions by the probe was studied in HeLa cells.

Coumarin-Based Fluorescence Probe for Differentiated Detection of Biothiols and Its Bioimaging in Cells.

In this work, a coumarin derivative, SWJT-14, was synthesized as a fluorescence probe to distinguish cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) in aqueous solutions. The detection limit of Cys, Hcy and GSH for the probe was 0.02 µM, 0.42 µM and 0.92 µM, respectively, which was lower than biothiols in cells. The probe reacted with biothiols to generate different products with different conjugated structures. Additionally, it could distinguish Cys, Hcy and GSH using fluorescence and UV-Vis spectra. The detection mechanism was confirmed by MS. SWJT-14 was successfully used in cellular experiments and detected both endogenous and exogenous biothiols.

A fluorescein-based fluorescent probe for fast detection of malondialdehyde and its imaging study.

A simple fluorescein derivative as a fluorescent probe was synthesized for the detection of malondialdehyde (MDA) through a synergistic reaction to achieve ring-opening of fluorescein and formation of a benzohydrazide derivative. It exhibited high sensitivity and selectivity for MDA detection. The probe could also detect MDA quickly (within 60 s) and visually via UV-vis and fluorescent modes. Moreover, this probe showed good performance in the imaging of MDA in living cells and bacteria.

Prognostic and clinicopathological significance of fatty acid synthase in breast cancer: A systematic review and meta-analysis.

Background: Aberrant expression of fatty acid synthase (FASN) was demonstrated in various tumors including breast cancer. A meta-analysis was conducted to investigate the role of FASN in breast cancer development and its potential prognostic significance. Methods: The Web of Science, PubMed, Embase, and Cochrane Library databases were searched to identify studies that evaluated the relationship between FASN expression and overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS) of breast cancer patients. To analyze the clinicopathological and prognostic values of FASN expression in breast cancer, pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were clustered based on random-effects models. To confirm whether the findings were stable and impartial, a sensitivity analysis was performed, and publication bias was estimated. Data were analyzed using Engauge Digitizer version 5.4 and Stata version 15.0. Results: Five studies involving 855 participants were included. Patients with higher FASN expression did not have a shorter survival period compared to those with lower FASN expression (summary HR: OS, 0.73 [95% CI, 0.41-1.32; P=0.300]; DFS/RFS, 1.65 [95% CI, 0.61-4.43; P=0.323]). However, increased FASN expression was correlated with large tumor size (OR, 2.04; 95% CI, 1.04-4.00; P=0.038), higher human epidermal growth factor receptor 2 (HER2) positivity (OR, 1.53; 95% CI, 1.05-2.23; P=0.028). No significant associations were observed between FASN expression and histological grade (OR, 0.92; 95% CI, 0.41-2.04; P=0.832), Tumor Node Metastasis (TNM) stage (OR, 1.11; 95% CI, 0.49-2.53; P=0.795), nodal metastasis (OR, 1.42; 95% CI, 0.84-2.38; P=0.183), Ki-67 labelling index (OR, 0.64; 95% CI, 0.15-2.63; P=0.533), estrogen receptor (ER) status (OR, 0.90; 95% CI, 0.61-1.32; P=0.586), or progesterone receptor (PR) status (OR, 0.67; 95% CI, 0.29-1.56; P=0.354). Conclusion: FASN is associated with HER2 expression and may contribute to tumor growth, but it has no significant impact on the overall prognosis of breast cancer.

A ratiometric, colorimetric fluorescent probe with a large emission shift for the rapid detection of diethyl chlorophosphate.

A new ratiometric and colorimetric probe (SWJT-16) based on the isophorone skeleton to detect diethyl chlorophosphite (DCP), a nerve agent mimic, was designed and synthesized. SWJT-16 underwent a nucleophilic substitution reaction with DCP in DMF, leading to a large emission shift (Δλem = 174 nm) accompanied by a significant color change from blue to yellow under visible light. All these changes occurred within 6 seconds, faster than those of most reported ratiometric fluorescent probes for DCP. Furthermore, SWJT-16 was successfully employed to monitor gaseous DCP.

Histopathologic study of keloid vascular structures shows the vascular origin pattern of keloid subepidermal vascular network flaps.

BACKGROUND: Keloid subepidermal vascular network flaps (KSVNFs) have achieved satisfactory results in clinical practice. Through this retrospective study, we further examined keloid vascular structure to better understand vascular origin pattern in KSVNFs. METHODS: Paraffin-embedded keloid tissues were stained for CD31. Distances from keloid subepidermal capillaries to the skin surface were measured. The included angle between the pedicle vessels and skin surface (angle PV), as well as the included angle between the keloid margin and skin surface (angle KM), were also measured. The major and minor axes of the capillary in the central areas of keloid (KDC), adjacent skin (AS) and marginal areas of keloid (KDM) were analyzed, and the major:minor axis ratios (M/m) were calculated. Vessels in KSVNF pedicle sites (KDP) were compared with vessels in adjacent skin as a subgroup analysis. RESULTS: Twenty-nine keloid specimens in total were collected. Based on 1630 measured data points, the capillary distance to the skin surface was 387.2±96.7 µm. The angle PV was 70.1±36.6°, and the angle KM was 67.0±18.1°. The major axis of the KDM capillaries was significantly longer than that of KDC and AS (both P < 0.001). The major and minor axes were longer in KDP than in AS (both P < 0.001). CONCLUSION: Suprakeloidal blood vessels are mainly distributed at a depth of 387.2±96.7 µm from the skin. The subepidermal plexus in KSVNF pedicle sites enters the skin at an acute angle and runs parallel to the keloid margin layer. Vessels in keloid marginal areas had crushed vascular lumen, but vessels in KSVNF pedicles did not.

A Turn-On and Colorimetric Probe Based on Isophorone Skeleton for Detecting Nerve Agent Mimic Diethyl Chlorophosphite.

A new turn-on probe (SWJT-20) based on isophorone fluorophore for the detection of nerve agent mimic diethyl chlorophosphite (DCP) was designed and synthesized. SWJT-20 could rapidly respond to DCP within 2 s using UV-Vis or fluorescent spectra, accompanied by a significant change in the solution color under visible light or UV light, which could be observed by the naked eyes. The detection limit of SWJT-20 to DCP was as low as 8.3 nM, which is lower than those of most reported fluorescent probes for DCP detection. Additionally, SWJT-20 could quantitatively measure DCP using ratio changes in A427/A645 in absorption spectra. Furthermore, facile paper as sensors with the visualization of colorimetric/fluorometric responses based on SWJT-20 has been fabricated. Notably, this probe could detect DCP vapor through gas diffusion experiments.