Advances in sarcoma molecular diagnostics.

Sarcomas are cancers of mesenchymal origin with the potential to arise in diverse anatomic locations. With over 80 subtypes, which often demonstrate overlapping morphologies, sarcomas frequently require ancillary testing to enable accurate classification. Pathognomonic driver mutations can often be leveraged for diagnostic purposes and include fusion genes, amplification events, and recurrent point mutations. Until relatively recently, the major clinical molecular diagnostic tests have been karyotyping, fluorescence in situ hybridization, and polymerase chain reaction; however, these techniques have a number of limitations. Recent technological advances have led to the development of more comprehensive assays with higher throughput, thereby replacing the need for a suite of single gene tests. These approaches include next-generation sequencing, fluorescent bar code hybridization, and DNA methylation profiling, among others. Herein, we review the application of recently developed techniques relevant to the diagnosis of sarcomas, and emerging assays with the potential for future development and clinical implementation.

Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis.

Outcomes for metastatic Ewing sarcoma and osteosarcoma are dismal and have not changed for decades. Oxidative stress attenuates melanoma metastasis, and melanoma cells must reduce oxidative stress to metastasize. We explored this in sarcomas by screening for oxidative stress sensitizers, which identified the class I HDAC inhibitor MS-275 as enhancing vulnerability to reactive oxygen species (ROS) in sarcoma cells. Mechanistically, MS-275 inhibits YB-1 deacetylation, decreasing its binding to 5'-UTRs of NFE2L2 encoding the antioxidant factor NRF2, thereby reducing NFE2L2 translation and synthesis of NRF2 to increase cellular ROS. By global acetylomics, MS-275 promotes rapid acetylation of the YB-1 RNA-binding protein at lysine-81, blocking binding and translational activation of NFE2L2, as well as known YB-1 mRNA targets, HIF1A, and the stress granule nucleator, G3BP1. MS-275 dramatically reduces sarcoma metastasis in vivo, but an MS-275-resistant YB-1K81-to-alanine mutant restores metastatic capacity and NRF2, HIF1α, and G3BP1 synthesis in MS-275-treated mice. These studies describe a novel function for MS-275 through enhanced YB-1 acetylation, thus inhibiting YB-1 translational control of key cytoprotective factors and its pro-metastatic activity.

Multi-Layer π-Stacked Molecules as Efficient Thermally Activated Delayed Fluorescence Emitters.

Multi-layer π-stacked emitters based on spatially confined donor/acceptor/donor (D/A/D) patterns have been developed to achieve high-efficiency thermally activated delayed fluorescence (TADF). In this case, dual donor moieties and a single acceptor moiety are introduced to form two three-dimensional (3D) emitters, DM-BD1 and DM-BD2, which rely on spatial charge transfer (CT). Owing to the enforced face-to-face D/A/D pattern, effective CT interactions are realized, which lead to high photoluminescence quantum yields (PLQYs) of 94.2 % and 92.8 % for the two molecules, respectively. The resulting emitters exhibit small singlet-triplet energy splitting (ΔEST ) and fast reverse intersystem crossing (RISC) processes. Maximum external quantum efficiencies (EQEs) of 28.0 % and 26.6 % were realized for devices based on DM-BD1 and DM-BD2, respectively, which are higher than those of their D/A-type analogues.

Remote Fluorination and Fluoroalkyl(thiol)ation Reactions.

Remote functionalization reactions have the power to transform a C-H (or C-C) bond at a distant position from a functional group. This Review summarizes recent advances and key breakthroughs in remote fluorination, trifluoromethylation, difluoromethylation, trifluoromethylthiolation, and fluoroalkenylation reactions. Several powerful strategies have emerged to control the reactivity and distal selectivity such as the undirected radical approach, the 1,5-hydrogen atom transfer, the metal migration, the use of distant directing groups, and the ring-opening reactions. These unconventional and predictable C-H (and C-C) functionalization transformations should allow for the preparation of a wide range of otherwise-difficult-to-access alkyl, aromatic, heteroaromatic, and structurally complex fluorides.

Genistein inhibits nasopharyngeal cancer stem cells through sonic hedgehog signaling.

Genistein, a soy derived isoflavanoid compound, exerts anticancer effects in various cancers. Nasopharyngeal cancer stem cells (NCSCs) are a small subpopulation of cancer cells which are responsible for initiation, progression, metastasis, and recurrence of nasopharyngeal cancer. The present study aimed to investigate the suppressive effects of genistein on NCSCs and its underlying mechanism. NCSCs were enriched from human nasopharyngeal cancer cell lines CNE2 and HONE1 through tumorsphere-forming assay. It was shown that genistein inhibited the tumorsphere formation capacity, decreased the number of EpCAM+ cells, downregulated the expression of NCSCs markers, suppressed cell proliferation, and induced apoptosis of NCSCs. Genistein suppressed the activity of Sonic hedgehog (SHH) signaling, which was important for the maintenance of NCSCs, while activation of SHH signaling by purmorphamine diminished the inhibitory effects of genistein on NCSCs. Our data suggested that genistein inhibited NCSCs through the suppression of SHH signaling. These findings support the use of genistein for targeting NCSCs.

Phenethyl isothiocyanate inhibits colorectal cancer stem cells by suppressing Wnt/ß-catenin pathway.

Cancer stem cells (CSCs) are considered to play essential roles in the process of origination, proliferation, migration, and invasion of cancer, and their properties are regulated by Wnt/ß-catenin pathway. Phenethyl isothiocyanate (PEITC) is a natural product obtained from cruciferous vegetables with anticancer activities. The present study aimed to investigate the inhibitory effect and the underlying mechanisms of PEITC on colorectal CSCs. In this study, we found that PEITC can significantly reduce the size and number of colorectal cancer cell spheroids in serum-free medium. With increasing PEITC concentrations (10-40 µM), the number of spheroids was reduced to about 10% of the control group, and the percentage of CD133+ cells was decreased by about 3-16 folds. PEITC also decreased the expression of CSC markers. Meanwhile, inhibition of proliferation as well as induction of apoptosis of colorectal CSCs was observed after PEITC treatment. Furthermore, through activating Wnt/ß-catenin pathway with LiCl, the inhibitory effects of PEITC on colorectal CSCs were diminished. Our data suggested that PEITC can be an effective inhibitor of colorectal CSCs by targeting Wnt/ß-catenin pathway.

[Research on Ground Feature's Polarized Properties with Multi-Spectral and Multi-Angle AirMSPI Data].

Polarization is an important characteristic of electromagnetic wave, and using polarization information to study ground features has been proved to be an effective means. Research on ground feature's polarized properties is an essential part of earth observation. At present, it is in highly need of accurate polarization sensors globally. AirMSPI , (Airborne Multiangle Spectro-Polarimetric Imager) as a new airborne polarized sensor, can obtain multi-band and multi-angle polarization data, and the spatial resolution can reach to ~10 meters. Using the experimental data of Tracy in the year of 2013, this paper analyzes the varying pattern of DOLP (Degree of Linear Polarization) as well as pBRF(polarized Bidirectional Reflectance Factor) in 470 nm, 660 nm, 865 nm bands and 9 view zenith angles. The result shows that, forward scattering of ground features contains plenty of polarized radiation, and ground features present strong non-lambertian effect near principal plane of incidence. DOLP and pBRF has strong correlation to relative position between incidence and view angle. DOLP reaches the maximum value when two directions are perpendicular while pBRF increases with larger view zenith angle. Because of atmospheric effect, radiance of blue band contains most polarized light. However, red and infrared band can attenuate atmospheric molecular polarization scattering effectively, thus contain more polarization details of ground features. Water, artificial structure, residential area, bare soil and vegetation show distinct polarization characteristics, and can be clearly identified. Due to depolarization effect from multi-scattering effect, DOLP and reflected radiation intensity have highly negative correlation, with correlation coefficient generally more than -0.8. AirMSPI sensor can provide high-quality polarization data, as a strong verification to ground-based and satellite-based polarization data, and support parameters inversion of atmosphere and ground features.

SLC7A11 as a therapeutic target to attenuate phthalates-driven testosterone level decline in mice.

INTRODUCTION: Phthalates exposure is a major public health concern due to the accumulation in the environment and associated with levels of testosterone reduction, leading to adverse pregnancy outcomes. However, the relationship between phthalate-induced testosterone level decline and ferroptosis remains poorly defined. OBJECTIVES: Herein, we aimed to explore the mechanisms of phthalates-induced testosterone synthesis disorder and its relationship to ferroptosis. METHODS: We conducted validated experiments in vivo male mice model and in vitro mouse Leydig TM3 cell line, followed by RNA sequencing and metabolomic analysis. We evaluated the levels of testosterone synthesis-associated enzymes and ferroptosis-related indicators by using qRT-PCR and Western blotting. Then, we analyzed the lipid peroxidation, ROS, Fe2+ levels and glutathione system to confirm the occurrence of ferroptosis. RESULTS: In the present study, we used di (2-ethylhexyl) phthalate (DEHP) to identify ferroptosis as the critical contributor to phthalate-induced testosterone level decline. It was demonstrated that DEHP caused glutathione metabolism and steroid synthesis disorders in Leydig cells. As the primary metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP) triggered testosterone synthesis disorder accompanied by a decrease in the expression of solute carri1er family 7 member 11 (SLC7A11) protein. Furthermore, MEHP synergistically induced ferroptosis with Erastin through the increase of intracellular and mitochondrial ROS, and lipid peroxidation production. Mechanistically, overexpression of SLC7A11 counteracts the synergistic effect of co-exposure to MEHP-Erastin. CONCLUSION: Our research results suggest that MEHP does not induce ferroptosis but synergizes Erastin-induced ferroptosis. These findings provide evidence for the role of ferroptosis in phthalates-induced testosterone synthesis disorder and point to SLC7A11 as a potential target for male reproductive diseases. This study established a correlation between ferroptosis and phthalates cytotoxicity, providing a novel view point for mitigating the issue of male reproductive disease and "The Global Plastic Toxicity Debt".

Study on the equity of urban green space: Origin, progress, and enlightenment.

Urban green space equity focuses on whether different social groups can equally share the well-being from green space, which is an important issue in the realm of environmental justice. We systematically introduced the origin and development of green space equity, explored its multidimensional progress in conceptual connotation, measurement methodology, phenomenon, mechanism, and regulation, and proposed the enlightenment for deepening the related studies. The green space equity originated from environmental social movement and environmental justice studies, and experienced multilevel evolution in topic constriction and theoretical interpretation. Although the connotation of green space equity was interpreted from various perspectives, its core idea was distributional equality. There was a frequently-used framework for measurement methodology of green space equity, whose spatial scale issue was critical. Due to the differences of characteristics, developmental stages, and institutional backgrounds between Chinese and Western cities, the phenomena and driving mechanisms of green space equity were different. The regulation strategies of green space equity could be summarized into three types, including green distributional equitable strategy, social recognitional justice strategy, and procedural justice orientated strategy. Future studies should deepen the research from the hierarchical logics for practice management, the fine-scale measurement methodology, the interpretation of mechanism for green space inequity in Chinese context, and simulation of differentiated regulation strategies. Social development endows green space equity with more practical tasks and theoretical logics, which is urgent to clarify the research progress to support the future research.

Thermal necrosis in orthopedic bone tumors: experimental research.

Introduction: The extent of surgical resection in orthopedic oncology differs according to tumor biology. While malignant bone tumors are operatively managed with wide resection, benign bone tumors and metastatic carcinomas are often treated through intralesional excision and adjuvant modalities, including the elimination of residual neoplastic cells through thermal necrosis. This study investigates in vitro temperature thresholds for thermal necrosis in common orthopedic bone tumors. Methodology: Eleven cell lines, including metastatic carcinomas to bone (A549, A498, FU-UR-1, PC3, MDA-MB-231, TT, MCF7, and K1), giant cell tumor of bone, osteosarcoma (HG-63), and control non-neoplastic cells (HEK293) were cultured. Cells were exposed to thermal stress at varying times and temperatures and evaluated for survival and viability with crystal violet and MTT assays. Results: Both the MTT and crystal violet assay demonstrated statistically superior rates of viability and survival for A549 (lung carcinoma), FU-UR-1 (renal carcinoma), K1 (thyroid carcinoma), and MG-63 (osteosarcoma) cell lines compared to control (HEK293 cells) at 60°C. Additionally, the MTT assay demonstrated superior viability for PC3 (prostate carcinoma), MCF7 (breast carcinoma), and A498 (renal carcinoma) compared to control. All cell lines demonstrated significantly decreased survival and viability in temperatures more than 90°C. Conclusion: This study demonstrated in vitro thresholds for thermal necrosis for cell lines of common orthopedic tumors of bone. The A549 (lung carcinoma), K1 (thyroid carcinoma), and FU-UR-1 (renal carcinoma) cell lines demonstrated greater resistance to heat stress compared to non-neoplastic control cells. Temperatures in excess of 90°C are necessary to reliably reduce cell survival and viability to less than 10%.

Iron-Catalyzed Alkoxyl Radical-Induced C-C Bond Cleavage/gem-Difluoroalkylation Cascade.

An inexpensive iron-catalyzed alkoxyl radical-induced C-C bond cleavage/gem-difluoroalkylation cascade is presented. Regulated by the structure of alkoxyl radical precursors, fluorinated distal diketones were synthesized through a ring-opening strategy and difluoroalkylated medium-sized lactones and macrolactones were constructed via a ring-expansion strategy. Both protocols proceeded under mild and redox neutral conditions with a broad substrate scope and good functional group compatibility.

High-intensity interval training alleviates exhaustive exercise-induced HSP70-assisted selective autophagy in skeletal muscle.

This study was designed to probe the effect of chaperone-assisted selective autophagy (CASA) on the maintenance of proteostasis during exhaustive exercise and uncover the alteration of CASA in muscle fibers with pre-high-intensity interval training (HIIT) intervention-induced muscle adaptation in response to exhaustive exercise. Rats were randomly divided into a control group; an exhaustive exercise group; and an HIIT + exhaustive exercise group. Results show myofibril damage and BiP levels were increased after exhaustive exercise, and the levels of the HSP70, BAG3, ubiquitin, autophagy-related proteins, and their interactions were increased. HIIT intervention before exhaustive exercise could decrease myofibril injury and BiP levels, accompanied by down-regulation of HSP70/BAG3 complex and selective autophagy. In conclusion, exhaustive exercise promotes CASA to clear protein aggregation for keeping proteostasis in muscle fibers; pre-HIIT intervention improves myofibril injury and unfold protein response caused by exhaustive exercise, which might contribute to inhibit the augmentation of CASA.

Design and Synthesis of Red Through-Space Charge Transfer Thermally Activated Delayed Fluorescence Emitters with Donor/Acceptor/Donor Stacking.

Red through-space charge transfer thermally activated delayed fluorescence (TSCT TADF) materials named SAF36DCPP and SAF27DCPP with sandwiched structures were synthesized. Single crystals indicated that the intramolecular C-H···π interactions play a vital role in rigidifying the sandwiched structure, which results in a fluorescence yield of 63% for SAF36DCPP compared to 40% for SAF27DCPP. Organic light-emitting diodes with SAF36DCPP as the emitter realized a maximum external quantum efficiency of 16.12%.

Application of E-coach chronic disease management model in rehabilitation management of patients with arteriosclerosis obliterans.

OBJECTIVE: To explore the effect of a health (E)-coach chronic disease management model on the rehabilitation behaviour management of patients with arteriosclerosis obliterans (ASO). METHODS: The E-coach chronic disease management model was constructed based on a literature review and expert interviews. The effect of the E-coach model on patients with ASO during hospitalisation was analysed by comparing the compliance rates of blood glucose control, blood pressure control, drug compliance, ankle-brachial index, 6-min walking test (6MWT) and pain-free walking distance (PFWD) scores between the E-coach and control groups. RESULTS: In total, 212 patients with ASO were included in this study. After the intervention, the blood pressure compliance rate (44.8% vs. 65.7%) and blood glucose compliance rate (48.6% vs. 66.8%) were higher in the E-coach group than in the control group (p < 0.05). After intervention, compared with the control group, the patients in the E-coach group had better drug compliance (6.8 ± 1.9 vs. 7.9 ± 1.0), and the difference was statistically significant (p < 0.05). The scores for the 6MWT (329.19 ± 5.58 vs. 353.00 ± 9.76; 412.65 ± 12.59 vs. 499.16 ± 18.43) and PFWD (219.15 ± 11.96 vs. 225.36 ± 16.13; 331.62 ± 51.36 vs. 369.42 ± 75.71) tests were significantly higher in the E-coach group than in the control group at 1 and 6 months after intervention (p < 0.05). CONCLUSION: The E-coach chronic disease management model can effectively improve the control rates of blood glucose and blood pressure and the behaviour management of patients with ASO and is thus worthy of clinical reference.

Ion-Dipole Interaction Enabling Highly Efficient CsPbI3 Perovskite Indoor Photovoltaics.

Metal halide perovskites are ideal candidates for indoor photovoltaics (IPVs) because of their easy-to-adjust bandgaps, which can be designed to cover the spectrum of any artificial light source. However, the serious non-radiative carrier recombination under low light illumination restrains the application of perovskite-based IPVs (PIPVs). Herein, polar molecules of amino naphthalene sulfonates are employed to functionalize the TiO2 substrate, anchoring the CsPbI3 perovskite crystal grains with a strong ion-dipole interaction between the molecule-level polar interlayer and the ionic perovskite film. The resulting high-quality CsPbI3 films with the merit of defect-immunity and large shunt resistance under low light conditions enable the corresponding PIPVs with an indoor power conversion efficiency of up to 41.2% (Pin : 334.11 µW cm-2 , Pout : 137.66 µW cm-2 ) under illumination from a commonly used indoor light-emitting diode light source (2956 K, 1062 lux). Furthermore, the device also achieves efficiencies of 29.45% (Pout : 9.80 µW cm-2 ) and 32.54% (Pout : 54.34 µW cm-2 ) at 106 (Pin : 33.84 µW cm-2 ) and 522 lux (Pin : 168.21 µW cm-2 ), respectively.

In Situ Inorganic Ligand Replenishment Enables Bandgap Stability in Mixed-Halide Perovskite Quantum Dot Solids.

Instability in mixed-halide perovskites (MHPs) is a key issue limiting perovskite solar cells and light-emitting diodes (LEDs). One form of instability arises during the processing of MHP quantum dots using an antisolvent to precipitate and purify the dots forming surface traps that lead to decreased luminescence, compromised colloidal stability, and emission broadening. Here, the introduction of inorganic ligands in the antisolvents used in dot purification is reported in order to overcome this problem. MHPs that are colloidally stable for over 1 year at 25 °C and 40% humidity are demonstrated and films that are stable under 100 W cm-2 photoirradiation, 4× longer than the best previously reported MHPs, are reported. In LEDs, the materials enable an EQE of 24.4% (average 22.5 ± 1.3%) and narrow emission (full-width at half maximum of 30 nm). Sixfold-enhanced operating stability relative to the most stable prior red perovskite LEDs having external quantum efficiency >20% is reported.

Status of diagnosis and treatment of esophageal cancer and non-coding RNA correlation research: a narrative review.

OBJECTIVE: To describe and discuss the progression of the non-coding RNA as biomarkers in early esophageal cancer. BACKGROUND: Esophageal cancer without obvious symptoms during early stages is one of the most common cancers, the current clinical treatments offer possibilities of a cure, but the survival rates and the prognoses remain poor, it is a serious threat to human life and health. Most patients are usually diagnosed during terminal stages due to low sensitivity of esophageal cancer's early detection techniques. With the development of molecular biology, an increasing number of non-coding RNAs are found to be associated with the occurrence, development, and prognosis of esophageal cancer. Some of these have begun to be used in clinics and laboratories for diagnosis, treatment, and prognosis, with the goal of reducing mortality. METHODS: The information for this paper was collected from a variety of sources, including a search of the keynote's references, a search for texts in college libraries, and discussions with experts in the field of esophageal cancer clinical treatment. CONCLUSIONS: Non-coding RNA does play a regulatory role in the development of esophageal cancer, which can predict the occurrence or prognosis of tumors, and become a new class of tumor markers and therapeutic targets in clinical applications. In this review, we survey the recent developments in the incidence, diagnosis, and treatment of esophageal cancer, especially with new research progresses on non-coding RNA biomarkers in detail, and discuss its potential clinical applications.

Harvesting triplet excitons for near-infrared electroluminescence via thermally activated delayed fluorescence channel.

Near-infrared (NIR) emission is useful for numerous practical applications, such as communication, biomedical sensors, night vision, etc., which encourages researchers to develop materials and devices for the realization of efficient NIR organic light-emitting devices. Recently, the emerging organic thermally activated delayed fluorescence (TADF) emitters have attracted wide attention because of the full utilization of electron-generated excitons, which is crucial for achieving high device efficiency. Up to now, the TADF emitters have shown their potential in the deep red/NIR region. Considering the color purity and efficiency, however, the development of NIR TADF emitters still lags behind RGB TADF emitters, indicating that there is still much room to improve their performance. In this regard, this perspective mainly summarizes the past progress of molecular design on constructing TADF NIR emitters. We hope this perspective could provide a new vista in developing NIR materials and enlighten breakthroughs in both fundamental research and applications.

Establishment and evaluation of a nomogram prediction model for recurrence risk of atrial fibrillation patients after radiofrequency ablation.

OBJECTIVE: To explore the risk factors for recurrence of atrial fibrillation (AF) in patients after radiofrequency ablation and construction of a targeted nomogram prediction model. METHODS: A prospective cohort study design was used to select 312 patients who were separated into two groups; a recurrence group (n = 79) and a non-recurrence group (n = 233) with or without AF, who underwent radiofrequency ablation for the first time between January 2017 and December 2017, with a completed a 12-month follow-up after surgery. The recurrence of AF within 12 months after follow-up was recorded. The nomogram prediction model was established. The original data were resampled using the Bootstrap method. The recurrence risk after resampling was predicted using a nomogram model. The calibration curve and ROC curve of the nomogram model were established. The predicted calibration degree and discrimination degree of the nomogram model were evaluated with the Hosmer-Lemeshow deviation test and area under the curve. RESULTS: The 12-month follow-up showed that a total of 79 patients (25.32%) had recurrence of AF. The type of AF, sex, gender, disease course, left atrial anteroposterior diameter, left atrial volume, and cardiac function classification were independent risk factors for the recurrence of AF (P < 0.05). After the nomogram prediction model passed the Bootstrap self-sampling 1000 times, Hosmer-Lemeshow deviation test: χ2 = 8.070, P = 0.427; the area under ROC curve was 0.852 (95% CI: 0.806-0.898), the sensitivity was 78.48%, and the specificity was 81.12%, suggesting that the nomogram model has better predictive calibration and discrimination. CONCLUSION: The recurrence rate in patients with AF after radiofrequency ablation is high. The nomogram model based on the risk factors of AF recurrence has high prediction accuracy and can be used to predict the recurrence risk of AF in patients after radiofrequency ablation.

Homoleptic Ir(III) Phosphors with 2-Phenyl-1,2,4-triazol-3-ylidene Chelates for Efficient Blue Organic Light-Emitting Diodes.

In this report, we synthesized two series of deep-blue-emitting homoleptic iridium(III) phosphors bearing 1,2,4-triazol-3-ylidene and 5-(trifluoromethyl)-1,2,4-triazol-3-ylidene cyclometalate. Compared with reported synthetic routes using Ag2O as the promoter, herein, we adopted a different strategy to furnish these complexes in high yields. Also, the meridional to facial isomerization was executed in the presence of trifluoroacetic acid. These phosphors were examined using NMR spectroscopies, single-crystal X-ray diffraction studies, and photophysical methods. The results revealed that electron-withdrawing trifluoromethyl substitution on the N-heterocyclic carbene fragment only gave a minor variation of photoluminescence peak wavelengths and a decrease in radiative lifetime but notable reduction in thermal stabilities. The parent 1,2,4-triazol-3-ylidene complexes have been demonstrated to be suitable for use as deep-blue phosphors, with structured emission with the peak max. located at ∼420 nm and with photoluminescence quantum yields in a range of 34.8-42.5% in degassed THF solution at RT. Fabrication of both the phosphorescent organic light-emitting diodes (OLEDs) and phosphor-sensitized OLEDs (or hyperphosphorescence) was successfully conducted, from which the OLED device based on m-tz1 showed a max. external quantum efficiency (EQE) of 10% with CIEx,y coordinates of 0.15, 0.06, while the corresponding hyperphosphorescent OLED using m-tz2 as a sensitizer and t-DABNA as a terminal emitter afforded a significantly improved max. EQE of 19.7%, EL λmax of 468 nm, and FWHM of 31 nm with CIEx,y coordinates of 0.12, 0.13.