Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.

Stark Effects of Rydberg Excitons in a Monolayer WSe2 P-N Junction.

The enhanced Coulomb interaction in two-dimensional semiconductors leads to tightly bound electron-hole pairs known as excitons. The large binding energy of excitons enables the formation of Rydberg excitons with high principal quantum numbers (n), analogous to Rydberg atoms. Rydberg excitons possess strong interactions among themselves as well as sensitive responses to external stimuli. Here, we probe Rydberg exciton resonances through photocurrent spectroscopy in a monolayer WSe2 p-n junction formed by a split-gate geometry. We show that an external in-plane electric field not only induces a large Stark shift of Rydberg excitons up to quantum principal number 3 but also mixes different orbitals and brightens otherwise dark states such as 3p and 3d. Our study provides an exciting platform for engineering Rydberg excitons for new quantum states and quantum sensing.

Air-Stable Self-Driven UV Photodetectors on Controllable Lead-Free CsCu2I3 Microwire Arrays.

The rapid evolution of the Internet of Things has engendered increased requirements for low-cost, self-powered UV photodetectors. Herein, high-performance self-driven UV photodetectors are fabricated by designing asymmetric metal-semiconductor-metal structures on the high-quality large-area CsCu2I3 microwire arrays. The asymmetrical depletion region doubles the photocurrent and response speed compared to the symmetric structure device, leading to a high responsivity of 233 mA/W to 355 nm radiation. Notably, at 0 V bias, the asymmetric device produces an open-circuit voltage of 356 mV and drives to a short-circuit current of 372 pA; meanwhile, the switch ratio (Iph/Idark) reaches up to 103, indicating its excellent potential for detecting weak light. Furthermore, the device maintains stable responses throughout 10000 UV-light switch cycles, with negligible degradation even after 90-day storage in air. Our work establishes that CsCu2I3 is a good candidate for self-powered UV detection and thoroughly demonstrates its potential as a passive device.

Functions of Phytochrome Interacting Factors (PIFs) in Adapting Plants to Biotic and Abiotic Stresses.

Plants possess the remarkable ability to sense detrimental environmental stimuli and launch sophisticated signal cascades that culminate in tailored responses to facilitate their survival, and transcription factors (TFs) are closely involved in these processes. Phytochrome interacting factors (PIFs) are among these TFs and belong to the basic helix-loop-helix family. PIFs are initially identified and have now been well established as core regulators of phytochrome-associated pathways in response to the light signal in plants. However, a growing body of evidence has unraveled that PIFs also play a crucial role in adapting plants to various biological and environmental pressures. In this review, we summarize and highlight that PIFs function as a signal hub that integrates multiple environmental cues, including abiotic (i.e., drought, temperature, and salinity) and biotic stresses to optimize plant growth and development. PIFs not only function as transcription factors to reprogram the expression of related genes, but also interact with various factors to adapt plants to harsh environments. This review will contribute to understanding the multifaceted functions of PIFs in response to different stress conditions, which will shed light on efforts to further dissect the novel functions of PIFs, especially in adaption to detrimental environments for a better survival of plants.

Accurate Intervertebral Disc Segmentation Approach Based on Deep Learning.

Automatically segmenting specific tissues or structures from medical images is a straightforward task for deep learning models. However, identifying a few specific objects from a group of similar targets can be a challenging task. This study focuses on the segmentation of certain specific intervertebral discs from lateral spine images acquired from an MRI scanner. In this research, an approach is proposed that utilizes MultiResUNet models and employs saliency maps for target intervertebral disc segmentation. First, a sub-image cropping method is used to separate the target discs. This method uses MultiResUNet to predict the saliency maps of target discs and crop sub-images for easier segmentation. Then, MultiResUNet is used to segment the target discs in these sub-images. The distance maps of the segmented discs are then calculated and combined with their original image for data augmentation to predict the remaining target discs. The training set and test set use 2674 and 308 MRI images, respectively. Experimental results demonstrate that the proposed method significantly enhances segmentation accuracy to about 98%. The performance of this approach highlights its effectiveness in segmenting specific intervertebral discs from closely similar discs.

Septin9 DNA methylation is associated with breast cancer recurrence or metastasis.

OBJECTIVE: We aimed to explore the prognostic value of Septin9 DNA methylation in breast cancer. METHODS: Breast cancer patients with and without recurrence or metastasis and matched non-breast cancer patients were screened retrospectively from 2014 to 2016. Bisulfite conversion and fluorescence quantitative methylation-specific polymerase chain reaction were used to detect the Septin9 methylation status and distribution levels in patient breast tissues. RESULTS: Septin9 DNA methylation was more frequent in breast cancer tissues than in non-breast cancer tissues, but was not significantly correlated with any relevant breast cancer patient clinicopathological characteristic. Septin9 methylation rates were higher in patients with recurrence or metastasis. Septin9 methylation, tumor size, lymph node status, and progesterone receptor (PR) expression could influence prognosis. Septin9 methylation was significantly associated with worse disease-free survival in breast cancer patients, with receiver operating characteristic curve analysis indicating that it had good prognostic ability, with an area under the curve (AUC) value of 0.719. The AUC values increased when Septin9 methylation was combined with tumor size, lymph node status, and PR to predict prognosis. CONCLUSIONS: Septin9 DNA methylation was an independent predictors of breast cancer prognostic risk. This could possibly help improve comprehensive prognosis prediction methods when combined with other risk factors.

Antidepressant duloxetine hydrochloride protects against ovariectomy-induced bone loss in mice by inhibiting osteoclast differentiation.

BACKGROUND: Several studies have reported the association between osteoporosis and major depressive disorder (MDD) as well as the use of antidepressants. However, it remains to be elucidated whether these associations are related to exposure to antidepressants, a consequence of a disease process, or a combination of both. METHODS: This study investigates the independent effect of the antidepressant duloxetine hydrochloride (DH) on ovariectomy-induced bone loss in mice. One week after ovariectomy, the treated mice received DH. To explore the mechanism underlying the rescue of bone loss, bone marrow cells were isolated from mouse femurs and tibias, and macrophages extracted from them were induced to become osteoclasts in vitro while being treated with DH. Subsequently, the osteoclasts underwent Bulk RNA-Seq to reveal the involved signaling pathways. The results of the bioinformatic analysis were then validated through in vitro experiments. RESULTS: The in vivo experiments demonstrated that DH treatment compromised ovariectomy-induced bone loss after 7 weeks. The in vitro experiments suggested that DH treatment attenuated osteoclast differentiation via the MAPKs/NFATc1 signaling pathway. CONCLUSION: The findings from this study suggest that DH, instead of causing bone mass loss, may assist in alleviating postmenopausal osteoporosis. These results can serve as a reference for the clinical treatment of patients with perimenopausal or postmenopausal depression using antidepressants.

Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

[Effects of miR-143 on the migration and invasion of osteosarcoma cells by regulating MMP-13 expression].

OBJECTIVE: To explore the effect of miR-143 regulating matrix metalloproteinase(MMP)-13 expression on migration and invasion of osteosarcoma cells. METHODS: The mouse osteosarcoma cell line 143B cells were cultured in 96-well plates, and blank group, negative group, positive group, and intervention group were set up. Then, the blank group did no treatment 50 µg miR-143 mimic was added to positive group, negative group added equal mimic NC (control sequence of miR-143 mimic), the intervention group was added 50 µg miR-143 mimic and 10 µg MMP-13 protein, all groups continued to culture for 3 to 6 hours, and finally the serum was aspirated to treat for half an hour. The protein expressions of miR-143 and MMP-13 in each group were measured by fluorescence quantitative PCR experiment and Western blot experiment, respectively, and the invasion and migration abilities of cells were measured by Transwell and scratch experiments. RESULTS: The expression of MMP-13 protein in the positive group and the intervention group was significantly lower than that in the blank group, and the positive group was lower than the intervention group (P<0.05);The mean numbers of invasive cells in blank group, negative group, positive group and intervention group were (1 000.01±44.77), (959.25±46.32), (245.04±4.33), (634.06±33.78) cells/field, respectively;the scratch healing rate of the positive group and the intervention group was significantly lower than that of the blank group, and the positive group was lower than the intervention group (P<0.05). CONCLUSION: MMP-13 is a target of miR-143, which can reduce the migration and invasion ability of osteosarcoma cells by inhibiting the expression of MMP-13.

Global Trends in Research of Perioperative Analgesia Over Past 10 Years: A Bibliometric Analysis.

Background: The postoperative acute pain caused by surgery has been a major problem plaguing anesthesiologists, and even some acute pain progresses to chronic pain syndrome, terribly reducing the quality of life of patients. To this end, increasing attention has been paid to the management of perioperative analgesia. At present, with the increase of research on perioperative analgesia, the understanding and solution of this clinical problem have been further developed. Bibliometrics can estimate research hot-spots and trends of related fields in a certain period of time. However, a systematic bibliometric analysis has not been conducted to explore current research hotspots and future development trends, which is thus the purpose of this study. Methods: Articles and reviews published from 2012 to 2021 were retrieved from the Web of Science Core Collection (WoSCC) database, and the bibliometric analysis of the keywords and references of articles was performed using VOSviewer1.6.18. Besides, the number of articles related to perioperative analgesia in term of countries, affiliations, authors, and journals were analyzed. Results: Finally, 3157 articles meeting the screening requirements were retrieved, and it was hereby found that the research on perioperative analgesia had received more attention and interest in the past 10 years, with the United States making more contributions, where there were eight of the top ten affiliations by the number of publications. Kaye AD was the most active researcher in this field. Most related articles were published in Anesthesia and Analgesia, accounting for 2.76% of all literature. Enhanced recovery after surgery, different types of anesthesia and multi-mode analgesic drug intervention were the main trends and hotspots. Conclusion: Perioperative analgesia has attracted considerable academic interest. In the past decade, the effects of enhanced recovery after surgery, different types of anesthesia and multi-mode analgesic drug intervention on perioperative analgesia have become the research hotspots, which are also likely to be the focus of future study.

Quantum control of field-free molecular orientation.

Generating field-free (non-stationary) orientation of molecules in space has been a longstanding goal in the field of quantum control of molecular rotation, which has significant applications in physical chemistry, chemical physics, strong-field physics, and quantum information science. In this Perspective, we review and examine several representative control schemes developed in recent years and implemented in theoretical and experimental areas for generating field-free orientation of molecules. By conducting numerical simulations of different control schemes on the same molecular system, we demonstrate that quantum coherent control, specifically targeting a limited number of the lowest-lying rotational levels to achieve an optimal superposition, can result in a high degree of orientation. To this end, we provide an overview of our latest developed analytical method, which enables the precise design of terahertz field parameters through resonant excitation. This design approach facilitates the attainment of desired field-free orientations by optimizing the amplitudes and phases of rotational wave functions for the selected rotational levels. Finally, we outlook the significance of such progress in multiple frontier research fields, highlighting its potential applications in ultracold physics, quantum computation, quantum simulation, and quantum metrology.

Quadrupolar excitons and hybridized interlayer Mott insulator in a trilayer moiré superlattice.

Transition metal dichalcogenide (TMDC) moiré superlattices, owing to the moiré flatbands and strong correlation, can host periodic electron crystals and fascinating correlated physics. The TMDC heterojunctions in the type-II alignment also enable long-lived interlayer excitons that are promising for correlated bosonic states, while the interaction is dictated by the asymmetry of the heterojunction. Here we demonstrate a new excitonic state, quadrupolar exciton, in a symmetric WSe2-WS2-WSe2 trilayer moiré superlattice. The quadrupolar excitons exhibit a quadratic dependence on the electric field, distinctively different from the linear Stark shift of the dipolar excitons in heterobilayers. This quadrupolar exciton stems from the hybridization of WSe2 valence moiré flatbands. The same mechanism also gives rise to an interlayer Mott insulator state, in which the two WSe2 layers share one hole laterally confined in one moiré unit cell. In contrast, the hole occupation probability in each layer can be continuously tuned via an out-of-plane electric field, reaching 100% in the top or bottom WSe2 under a large electric field, accompanying the transition from quadrupolar excitons to dipolar excitons. Our work demonstrates a trilayer moiré system as a new exciting playground for realizing novel correlated states and engineering quantum phase transitions.

Exciton Superposition across Moiré States in a Semiconducting Moiré Superlattice.

Moiré superlattices of semiconducting transition metal dichalcogenides enable unprecedented spatial control of electron wavefunctions, leading to emerging quantum states. The breaking of translational symmetry further introduces a new degree of freedom: high symmetry moiré sites of energy minima behaving as spatially separated quantum dots. We demonstrate the superposition between two moiré sites by constructing a trilayer WSe2/monolayer WS2 moiré heterojunction. The two moiré sites in the first layer WSe2 interfacing WS2 allow the formation of two different interlayer excitons, with the hole residing in either moiré site of the first layer WSe2 and the electron in the third layer WSe2. An electric field can drive the hybridization of either of the interlayer excitons with the intralayer excitons in the third WSe2 layer, realizing the continuous tuning of interlayer exciton hopping between two moiré sites and a superposition of the two interlayer excitons, distinctively different from the natural trilayer WSe2.

Physical properties and structural characteristics of particulate matter emitted from a diesel engine fueled with biodiesel blends.

This research explores the influence of renewable fuels, including three kinds of biodiesel along with ethanol on the physical properties and structural characteristics of particulate matter (PM) emitted from a diesel engine in comparison with pure diesel. After adding 10 vol% of grape seed biodiesel, coffee biodiesel and eucalyptus oil into diesel, three biodiesel blended fuels (10% grape seed biodiesel (DGs10), 10% spent coffee ground biodiesel (DC10) and eucalyptus oil biodiesel (DEu10)) were produced and tested in this study. Besides, one ethanol blend containing 9 vol% of ethanol and 1 vol% of biodiesel (blend stabilizer) was also tested to do the comparison. In the present study, scanning transmission electron microscope (STEM) and scanning electron microscope (SEM) were employed for analyzing the microstructure, nanostructure and electron diffraction pattern of PM. Raman spectrometer (RS) was also used for the analysis of structural characterization of PM. In addition, several experimental instruments like microbalance, measuring cup, viscometer, oxygen bomb calorimeter and Gas Chromatography-Mass Spectrometer (GC-MS) were employed to detect the fuel properties, including density, heating value, viscosity, composition and cetane number. A conclusion can be drawn that both biodiesel blends and ethanol blend have a changing effect on the PM properties compared to pure diesel, where biodiesel blends have a slightly weaker influence than ethanol blend. Regarding the biodiesel blends, DGs10 has more impact than DC10 and DEu10 in changes of PM properties, particularly in the reduction of PM mass, making it a good candidate for renewable fuel for diesel engines.

Photosensitive Dielectric 2D Perovskite Based Photodetector for Dual Wavelength Demultiplexing.

Stacked 2D perovskites provide more possibilities for next generation photodetector with more new features. Compared with its excellent optoelectronic properties, the good dielectric performance of metal halide perovskite rarely comes into notice. Here, a bifunctional perovskite based photovoltaic detector capable of two wavelength demultiplexing is demonstrated. In the Black Phosphorus/Perovskite/MoS2 structured photodetector, the comprehensive utilization of the photosensitive and dielectric properties of 2D perovskite allows the device to work in different modes. The device shows normal continuous photoresponse under 405 nm, while it shows a transient spike response to visible light with longer wavelengths. The linear dynamic range, rise/decay time, and self-powered responsivity under 405 nm can reach 100, 38 µs/50 µs, and 17.7 mA W-1 , respectively. It is demonstrated that the transient spike photocurrent with long wavelength exposure is related to the illumination intensity and can coexist with normal photoresponse. Two waveband-dependent signals can be identified and used to reflect more information simultaneously. This work provides a new strategy for multispectral detection and demultiplexing, which can be used to improve data transfer rates and encrypted communications. This work mode can inspire more multispectral photodetectors with different stacked 2D materials, especially to the optoelectronic application of the wide bandgap, high dielectric photosensitive materials.

Ultraviolet photodetector based on RbCu2I3microwire.

Copper-based halide perovskites have shown great potential in lighting and photodetection due to their excellent photoelectric properties, good stability and lead-free nature. However, as an important piece of copper-based perovskites, the synthesis and application of RbCu2I3have never been reported. Here, we demonstrate the synthesis of high-quality RbCu2I3microwires (MWs) by a fast-cooling hot saturated solution method. The prepared MWs exhibit an orthorhombic structure with a smooth surface. Optical measurements show the RbCu2I3MWs have a sharp ultraviolet absorption edge with 3.63 eV optical band gap and ultra-large stokes shift (300 nm) in photoluminescence. The subsequent photodetector based on a single RbCu2I3MW shows excellent ultraviolet detection performance. Under the 340 nm illumination, the device shows a specific detectivity of 5.0 × 109Jones and a responsivity of 380 mA·W-1. The synthesis method and physical properties of RbCu2I3could be a guide to the future optoelectronic application of the new material.

Enhanced Optoelectronic Performance Induced by Ion Migration in Lead-Free CsCu2I3 Single-Crystal Microrods.

Lead-free perovskite has attracted great attention in realizing high-performance optoelectronic devices due to their excellent atmospheric stability and nontoxic characteristics. Although a pronounced ion migration effect has been observed in this new class of materials, its potential in enhancing the overall device performance is yet to be fully explored. In this work, we studied the effect of ion migrations on the carrier transport behavior and found that the recoverable migration process can contribute to enhancing the on/off ratio in a lead-free CsCu2I3 single-crystal microrod-based photodetector. In detail, we synthesized CsCu2I3 single-crystal microrods via an in-plane self-assembly supersaturated crystallization approach. These microrods with well-defined morphologies were then used to construct ultraviolet (UV)-band photodetectors, which outperform most reported lead-free perovskite photodetectors based on individual single crystals. Simultaneously, ion migration can result in asymmetric band bending in the two-terminal device, as confirmed by surface potential profiling with Kelvin probe force microscopy (KPFM). Such an effect can be harnessed to increase the on/off ratio by almost an order of magnitude. Furthermore, the lead-free CsCu2I3 single crystal exhibits excellent thermal and air stabilities. These findings demonstrate that the CsCu2I3 single-crystal microrods can be used in stable and efficient photodetection, and the ion migration effect can potentially be utilized for improving the optoelectronic performance of lead-free devices.

Efficacy and safety of EGFR inhibitors and radiotherapy in locally advanced non-small-cell lung cancer: a meta-analysis.

Aim: To assess the efficacy and safety of EGFR inhibitors combined with (chemo)radiotherapy in unresectable, locally advanced non-small-cell lung cancer. Materials & methods: A systematic review and meta-analysis of prospective trials was performed. Results: Twenty-eight studies of 1640 patients were included. In patients harboring EGFR-sensitive mutations, the pooled objective response rate, 1-year overall survival rate and 1-year progression-free survival rate of EGFR-TKIs + (chemo)radiotherapy were 0.803, 0.766 and 0.554, respectively. Compared with chemoradiotherapy, the addition of EGFR inhibitors did not significantly increase the risk of grade ≥3 pneumonitis and esophagitis. Conclusion: EGFR-tyrosine kinase inhibitors combined with (chemo)radiotherapy are tolerable and the clinical benefit is promising, especially in patients with EGFR-sensitive mutations.

The aim of this systemic review and meta-analysis was to assess the efficacy and safety of (chemo)radiotherapy combined with therapies targeting EGFR receptor, in unresectable, locally advanced non-small-cell lung cancer. Prospective clinical trials were searched and analyzed, and 28 studies of 1640 patients were included in this analysis. The results showed that the efficacy of (chemo)radiotherapy combined with tyrosine kinase inhibitors targeting EGFR, such as gefitinib and erlotinib, was promising, especially among patients harboring sensitive mutations in EGFR. Besides, this combination therapy was safe, which did not increase the risk of severe pneumonitis and esophagitis. Overall, tyrosine kinase inhibitors targeting EGFR combined with (chemo)radiotherapy are tolerable and the clinical benefit is promising, especially in patients with EGFR-sensitive mutations.

Tuning moiré excitons and correlated electronic states through layer degree of freedom.

Moiré coupling in transition metal dichalcogenides (TMDCs) superlattices introduces flat minibands that enable strong electronic correlation and fascinating correlated states, and it also modifies the strong Coulomb-interaction-driven excitons and gives rise to moiré excitons. Here, we introduce the layer degree of freedom to the WSe2/WS2 moiré superlattice by changing WSe2 from monolayer to bilayer and trilayer. We observe systematic changes of optical spectra of the moiré excitons, which directly confirm the highly interfacial nature of moiré coupling at the WSe2/WS2 interface. In addition, the energy resonances of moiré excitons are strongly modified, with their separation significantly increased in multilayer WSe2/monolayer WS2 moiré superlattice. The additional WSe2 layers also modulate the strong electronic correlation strength, evidenced by the reduced Mott transition temperature with added WSe2 layer(s). The layer dependence of both moiré excitons and correlated electronic states can be well described by our theoretical model. Our study presents a new method to tune the strong electronic correlation and moiré exciton bands in the TMDCs moiré superlattices, ushering in an exciting platform to engineer quantum phenomena stemming from strong correlation and Coulomb interaction.