A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma: Construction and analysis of a circRNA-mediated competing endogenous RNA network.

BACKGROUND: Hepatocellular carcinoma (HCC) has a poor long-term prognosis. The competition of circular RNAs (circRNAs) with endogenous RNA is a novel tool for predicting HCC prognosis. Based on the alterations of circRNA regulatory networks, the analysis of gene modules related to HCC is feasible. METHODS: Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC. Gene function, pathway, and protein interaction analyses were performed for the differentially expressed genes (DEGs) in this regulatory network. In the protein-protein interaction network, hub genes were identified and subjected to regression analysis, producing an optimized four-gene signature for prognostic risk stratification in HCC patients. Anti-HCC drugs were excavated by assessing the DEGs between the low- and high-risk groups. A circRNA-microRNA-hub gene subnetwork was constructed, in which three hallmark genes, KIF4A, CCNA2, and PBK, were subjected to functional enrichment analysis. RESULTS: A four-gene signature (KIF4A, CCNA2, PBK, and ZWINT) that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort was developed. CDK inhibitors, PI3K inhibitors, HDAC inhibitors, and EGFR inhibitors were predicted as four potential mechanisms of drug action (MOA) in high-risk HCC patients. Subsequent analysis has revealed that PBK, CCNA2, and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion, regulating microsatellite instability (MSI), and exerting an impact on HCC progression. CONCLUSIONS: The present study highlights the role of the circRNA-related regulatory network, identifies a four-gene prognostic signature and biomarkers, and further identifies novel therapy for HCC.

FAPbBr3@PbBr(OH) phosphor with high stability for anti-counterfeiting application via water induction.

Organic-inorganic hybrid perovskite nanocrystals have become a very widely used as semiconductor light-emitting materials. However, perovskite nanocrystals face stability challenges, which is a key factor hindering their application. In this paper, by introducing water into the synthesis of formamidinium lead bromide (FAPbBr3) perovskite, ultra-stable FAPbBr3@PbBr(OH) fluorescent material was prepared. The photoluminescence intensity of the material after the addition of water increased 2.9 times compared with that before the addition of water. The excellent green fluorescence emission was still maintained after four cycles of wash-dry treatment. Meanwhile, it also exhibits good ultraviolet and thermal stability. The above enhanced performance of FAPbBr3nanocrystals is attributed the protection of PbBr(OH). In addition, the prepared material can be used in anti-counterfeit patterns. The anti-counterfeit patterns have good color rendering and the luminous color has a high dependence on temperature. Both of these features make it very valuable for various fluorescent anti-counterfeiting labels.

Recent Advances in NIR or X-ray Excited Persistent Luminescent Materials for Deep Bioimaging.

Due to their persistent luminescence, persistent luminescent (PersL) materials have attracted great interest. In the biomedical field, the use of persistent luminescent nanoparticles (PLNPs) eliminates the need for continuous in situ excitation, thereby avoiding interference from tissue autofluorescence and significantly improving the signal-to-noise ratio (SNR). Although persistent luminescence materials can emit light continuously, the luminescence intensity of small-sized nanoparticles in vivo decays quickly. Early persistent luminescent nanoparticles were mostly excited by ultraviolet (UV) or visible light and were administered for imaging purposes through ex vivo charging followed by injection into the body. Limited by the low in vivo penetration depth, UV light cannot secondary charge PLNPs that have decayed in vivo, and visible light does not penetrate deep enough to reach deep tissues, which greatly limits the imaging time of persistent luminescent materials. In order to address this issue, the development of PLNPs that can be activated by light sources with superior tissue penetration capabilities is essential. Near-infrared (NIR) light and X-rays are widely recognized as ideal excitation sources, making persistent luminescent materials stimulated by these two sources a prominent area of research in recent years. This review describes NIR and X-ray excitable persistent luminescence materials and their recent advances in bioimaging.

W-doped VO2 for high-performance aqueous Zn-ion batteries.

Aqueous Zn-ion batteries (AZIBs) have become one of the most promising energy storage devices due to their high safety and low cost. However, the development of stable cathodes with fast kinetics and high energy density is the key to achieving large-scale application of AZIBs. In this work, W-doped VO2 (W-VO2) is developed by a one-step hydrothermal method. Benefiting from the pre-insertion of W6+ and the introduction of the W-O bond, accomplishing an expanded lattice spacing and a stable structure, both improved kinetics and long cycle life are achieved. The W-VO2 delivers a specific capacity of 340.2 mA h g-1 at 0.2 A g-1, an excellent high-rate capability with a discharge capacity of 186.9 mA h g-1 at 10 A g-1, and long-term cycling stability with a capacity retention of 76.5% after 2000 cycles. The electrochemical performance of the W-VO2 has been greatly improved, compared with the pure VO2. The W doping strategy proposed here also presents an encouraging pathway for developing other high-energy and stable cathodes.

Multifunctional Bi NSs@BSA Nanoplatform Guided by CT Imaging for Effective Photothermal Therapy.

Photothermal therapy (PTT) has attracted great attention as an anticancer treatment strategy. With the rapid development of nanomedicine, multifunctional inorganic nanophotothermal agents provide a new way to improve the effect of PTT. Herein, bovine serum albumin (BSA)-modified Bi nanosheets (Bi NSs) with good biocompatibility were synthesized by a facile redox and ball milling method and applied as a photothermal agent for the enhancement of PTT. Owing to the strong near-infrared absorption, Bi NSs exhibit high photothermal conversion efficiency (η = 36.17%) under 808 nm laser irradiation and can serve as a nanotherapeutic agent for cancer therapy. In addition, in vitro cell safety analysis also suggests that the toxicity of BSA-modified Bi NSs is negligible. Upon 808 nm irradiation, the uptake ability of tumor cells to Bi NSs@BSA has been improved. Moreover, Bi NSs@BSA also can be used as a good contrast agent for CT imaging and then to observe the distribution of materials in the tumor site. Finally, Bi NSs@BSA-mediated PTT results show a high ablation rate of A549 tumor cells both in vitro and in vivo. All results reveal that Bi NSs@BSA is a promising nanotherapeutic platform for PTT.

Long-term scalogram integrated with an iterative data augmentation scheme for acoustic scene classification.

In acoustic scene classification (ASC), acoustic features play a crucial role in the extraction of scene information, which can be stored over different time scales. Moreover, the limited size of the dataset may lead to a biased model with a poor performance for recordings from unseen cities and confusing scene classes. This paper proposes a long-term wavelet feature that captures discriminative long-term scene information. The extracted scalogram requires a lower storage capacity and can be classified faster and more accurately compared with classic Mel filter bank coefficients (FBank). Furthermore, a data augmentation scheme is adopted to improve the generalization of the ASC systems, which extends the database iteratively with auxiliary classifier generative adversarial neural networks (ACGANs) and a deep learning-based sample filter. Experiments were conducted on datasets from the Detection and Classification of Acoustic Scenes and Events (DCASE) challenges. The DCASE17 and DCASE19 datasets marked a performance boost of the proposed techniques compared with the FBank classifier. Moreover, the ACGAN-based data augmentation scheme achieved an absolute accuracy improvement of 6.10% on recordings from unseen cities, far exceeding classic augmentation methods.

Study on organic-inorganic hybrid perovskite nanocrystals with regular morphologies and their effect on photoluminescence properties.

Organic-inorganic hybrid perovskite nanocrystals have been widely studied for their excellent photoelectric properties. However, the irregular morphologies of organic-inorganic hybrid perovskite nanocrystals have limited application in the field of lighting and display. From this, the regular morphologies of nanospheres, nanorods, nanoplatelets and MAPbBr3 (MA = CH3NH3 +) nanocrystals have been synthesized by regulating the type and proportion of auxiliary ligands. The phase evolution, morphology and fluorescent properties were systematically studied by the various instruments of XRD, TEM, PL/UV-vis spectroscopy and fluorescence decay analysis. With the morphologies changing from nanospheres to nanoplatelets, the emission peaks of MAPbBr3 nanocrystals red-shifted, and the lifetimes have increased gradually. The underlying mechanisms were thoroughly investigated and elucidated. On this basis, the role of acid and amine in the synthesis of MAPbBr3 nanocrystals was systematically studied by regulating the ratio of oleic acid and N-octylamine. The fluorescence kinetics of MAPbBr3 nanocrystals were studied by femtosecond transient absorption spectroscopy, and the charge carrier relaxation mechanism was clarified. Furthermore, the effect of temperature on the fluorescence properties of the nanocrystal was investigated in detail. Organic-inorganic hybrid perovskite nanocrystals with morphologies-controlled and excellent fluorescence properties are expected to be widely used in lighting and display fields.

High-precision long-distance measurement with an intensity-modulated frequency comb.

We describe an improved synthetic wavelength method for high-precision long-distance measurement with a repetition-rate-locked femtosecond laser modulated by a fiber Mach-Zehnder electro-optic intensity modulator. Harmonics of the repetition rate accompanied with modulating sidebands will be generated via intermode beating, which will be utilized for high-precision ranging. The nonambiguity range is significantly extended with a relatively low modulation frequency, and the ambiguous distance is unwrapped by synchronous phase-shift measurements of a synthetic wavelength chain without any auxiliary measurement operation. Our experiment shows a precision better than 20 µm at 46 m range, and a high-precision translation stage is applied for preliminary test and proof-of-principle demonstration. The demonstrated system is simple and can be easily integrated, and it will find widespread applications in large-scale metrology such as large-volume manufacturing and precision formation flying.

Controlled Synthesis of Tb3+/Eu3+ Co-Doped Gd2O3 Phosphors with Enhanced Red Emission.

(Gd0.93-xTb0.07Eux)2O3 (x = 0⁻0.10) phosphors shows great potential for applications in the lighting and display areas. (Gd0.93-xTb0.07Eux)2O3 phosphors with controlled morphology were prepared by a hydrothermal method, followed by calcination at 1100 °C. XRD, FE-SEM, PL/PLE, luminescent decay analysis and thermal stability have been performed to investigate the Eu3+ content and the effects of hydrothermal conditions on the phase variation, microstructure, luminescent properties and energy transfer. Optimum excitation wavelength at ~308 nm nanometer ascribed to the 4f8-4f75d¹ transition of Tb3+, the (Gd0.93-xTb0.07Eux)2O3 phosphors display both Tb3+and Eu3+ emission with the strongest emission band at ~611 nm. For increasing Eu3+ content, the Eu3+ emission intensity increased as well while the Tb3+ emission intensity decreased owing to Tb3+→Eu3+ energy transfer. The energy transfer efficiencies were calculated and the energy transfer mechanism was discussed in detail. The lifetime for both the Eu3+ and Tb3+ emission decreases with the Eu3+ addition, the former is due to the formation of resonant energy transfer net, and the latter is because of contribution by Tb3+→Eu3+ energy transfer. The phosphor morphology can be controlled by adjusting the hydrothermal condition (reaction pH), and the morphological influence to the luminescent properties (PL/PLE, decay lifetime, etc.) has been studied in detail.

Roles of CYP2C19 Gene Polymorphisms in Susceptibility to POAG and Individual Differences in Drug Treatment Response.

BACKGROUND: The aim of this study was to investigate the roles of cytochrome P450 2C19 (CYP2C19) polymorphisms in primary open-angle glaucoma (POAG) susceptibility and individual responses to drug treatment. MATERIAL/METHODS: This case-control study consisted of 93 cases with POAG and 125 controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze CYP2C19 single-nucleotide polymorphisms (SNPs). After timolol treatment, patients were classified into side effect (SE) group and non-side effect (NSE) group. According to drug treatment responses, patients were divided into 3 groups: excellent group (Ex) (IOP ≥8 mm Hg); utility group (Ut) (5 0.05). Frequencies of extensive metabolizer phenotype and poor metabolizer phenotype or poor metabolizer phenotype and intermediate metabolizer phenotype were significantly different between the SE group and NSE group (both P<0.05). The distribution of intermediate metabolizer phenotype and extensive metabolizer phenotype were significantly different among Ex group, Ut group, and In group (all P<0.05). CONCLUSIONS: We found no evidence that CYP2C19 polymorphisms are associated with susceptibility to POAG. However, different CYP2C19 metabolizer phenotypes were identified and observed to have important effects on the individual differences in drug treatment response.

Downregulation of microRNA-586 Inhibits Proliferation, Invasion and Metastasis and Promotes Apoptosis in Human Osteosarcoma U2-OS Cell Line.

In this study, we aim to examine the association of microRNA-586 (miR-586) with osteosarcoma (OS) cell proliferation, apoptosis, invasion, and metastasis. U2-OS cell lines were divided into 4 groups: an miR-586 group, anti-miR-586 group, control group (empty plasmid) and blank group (no plasmid). qRT-PCR was used to detect miR-586 expression, cell counting kit-8 and EdU assays to detect cell proliferation, flow cytometry to detect cell cycle distribution, Annexin V/PI double staining to detect cell apoptosis, and the Transwell assay to detect cell invasion and metastasis. miR-586 expression was significantly higher in the miR-586 group but significantly lower in the anti-miR-586 group compared with the control and blank groups. Cell proliferation at 2-5 days after cell transfection and the EdU-positive cell number increased obviously in the miR-586 group but decreased clearly in the anti-miR-586 group. In the miR-586 group, cells at G0/G1 stage and apoptosis cells significantly decreased, while cells at G2/M and S stages and invasive and metastatic cells significantly increased compared to the control and blank groups; however, opposite trends were found in the anti-miR-586 group. Downregulation of miR-586 expression in OS may inhibit cell proliferation, invasion and metastasis, and promote cell apoptosis.

Synergistic effect of N- and F-codoping on the structure and photocatalytic performance of TiO2.

Three types of TiO2 nanostructures were synthesized via a facile hydrolysis method at 195°C. Effects of the preparation method and doping with N and F on the crystal structure and photocatalytic performance of TiO2 were investigated. The nanomaterials were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller porosimetry, ultraviolet-visible diffuse reflectance spectroscopy and fluorescent emission spectra. Their photo-catalytic activity was examined by the photodegradation of methylene blue in aqueous solution under both ultra-violet and visible light irradiation. The results show that nitrogen and fluorine co-doped anatase TiO2 had the characteristics of a smaller crystalline size, broader light absorption spectrum and lower charge recombination than pure TiO2. Most importantly, more efficient photocatalytic activity under both ultra-violet and visible light was observed. The obtained N-F-TiO2 nanomaterial shows considerable potential for water treatment under sunlight irradiation.

Growable design of passenger vehicle interior space based on FAHP and FQFD.

The increasingly shortened development cycle of smart vehicles has led to a qualitative shift in the nature of automotive products. Growing spatial design of vehicle interiors can effectively satisfy users' personalisation preferences and increase their willingness to buy, as well as mitigating the environmental pollution caused by the problem of rapid replacement. Considering the subjectivity and uncertainty of users' emotional needs, this study adopts the FAHP method to comprehensively analyse and rank the SET series of factors, then combines the grey correlation method with the correlation analysis of the areas related to the interior space of the automobile, constructs the sample of the interior space of the automobile and extracts the kansei words of the space sample. Intentional vocabulary mean scores were calculated to factor analyses through kansei engineering, next the fuzzy QFD quality house was built to make affective semantic design associations and derive design weights, which are then used to guide the design and ultimately realise the design of a dynamic automotive interaction scenario. The results of the study show that the integration of different theories can reduce the uncertainties in accessing users' emotional needs. At the same time, it can provide systematic guidance for the interaction design of a growable automobile in terms of multiple dimensions of interior space connectivity, spatial layout, and perceptual experience, as well as provide valuable suggestions for the subsequent development of interior spaces.

X-ray triggered scintillator versatile nanocatalytic platform for synergistic photodynamic/chemodynamic therapy.

Nanocatalysts with photodynamic therapy (PDT) and chemodynamic therapy (CDT) are excellent for tumor therapy. However, it is still challenging to achieve complete tumor eradication due to the drawbacks of limited penetration depth of intratumoural tissues, hypoxia and complexity of the tumor microenvironment (TME). Herein, we fabricated an integrated multifunctional nanoreactor (LuAG:Tb/Ce-RB@ZIF-8-Au2Pt-HA, LRZAPH) combining scintillating nanoparticles (SCNPs, LuAG:Tb/Ce), a metal-organic framework (ZIF-8), and bimetallic Au2Pt for X-ray-triggered PDT and dual noble-metal nanozyme catalyzed CDT. Such a nanoreactor not only significantly enhanced the PDT effect under X-ray irradiation through full resonance energy transfer from LuAG:Tb/Ce scintillator to Ross Bengal (RB), but also facilitated the reactive oxygen species (ROS) and oxygen (O2) production through the excellent peroxidase-like (POD-like) and catalase-like (CAT-like) catalytic properties of Au2Pt nanozymes. O2 also alleviates hypoxia in intratumoural tissues during coordinated PDT. In addition, the dissociation behavior of ZIF-8 with pH-responsive and targeted of hyaluronic acid (HA) in acidic TME significantly enhanced the therapeutic efficacy of LRZAPH nanocatalysts. Significantly, the high tumor growth inhibition rate of 93 % was revealed due to radiotherapy (RT)/PDT/CDT synergetic therapy in vivo, which minimized the toxic and side effects of conventional clinical radiotherapy/chemotherapy on human. The synergistic effect of LRZAPH nanocatalysts on PDT and catalytically induced CDT is expected to provide new pathways for effective treatment of deep tumors.

An updated review of epidemiological characteristics, immune escape, and therapeutic advances of SARS-CoV-2 Omicron XBB.1.5 and other mutants.

The rapid evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the emergence of new variants with different genetic profiles, with important implications for public health. The continued emergence of new variants with unique genetic features and potential changes in biological properties poses significant challenges to public health strategies, vaccine development, and therapeutic interventions. Omicron variants have attracted particular attention due to their rapid spread and numerous mutations in key viral proteins. This review aims to provide an updated and comprehensive assessment of the epidemiological characteristics, immune escape potential, and therapeutic advances of the SARS-CoV-2 Omicron XBB.1.5 variant, as well as other variants.

Clinical study of the combined use of dexmedetomidine and remifentanil in patients with coronary heart disease undergoing 3D laparoscopic surgery with EEG bispectral index monitoring.

OBJECTIVE: This study sought to investigate the safety and clinical outcomes associated with the combined administration of dexmedetomidine (Dex) and remifentanil (Rem) in patients with coronary heart disease undergoing three-dimensional (3D) laparoscopic surgery, with concurrent monitoring of the electroencephalography (EEG) bispectral index. METHODS: This study is of a retrospective nature and involved a total of 60 patients with coronary heart disease who underwent 3D laparoscopic surgery at our hospital between June 2020 and September 2021. In a double-blind manner, these patients were randomly assigned to two groups: the control group (Group I), which consisted of 30 patients, and the treatment group (Group II) receiving a combination of Dex and Rem, also comprising 30 patients. The study's primary objective was to compare and assess the treatment outcomes in these two patient groups. RESULTS: Patients in Group II who developed postoperative coronary heart disease experienced a significant reduction in blood pressure, heart rate, and electrocardiogram values (P<0.05). Additionally, Group II exhibited lower bispectral index (BIS) and visual analog scale (VAS) values (P<0.05). CONCLUSION: In patients with coronary heart disease undergoing 3D laparoscopic surgery, the intraoperative use of Dex combined with Rem anesthesia offers several advantages. It helps stabilize hemodynamics, reducing the risk of myocardial ischemia, and significantly alleviates postoperative pain, all without increasing the likelihood of adverse postoperative reactions. Furthermore, this approach effectively dampens the intraoperative and postoperative stress response, facilitating enhanced recovery after surgery (ERAS). Overall, the clinical impact is positive, safe, and reliable.

Kinetics of severe acute respiratory syndrome coronavirus 2 infection antibody responses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world, causing severe morbidity and mortality. Since the first reports of Coronavirus disease 2019 (COVID-19) in late 2019, research on the characteristics of specific humoral immunity against SARS-CoV-2 in patients with COVID-19 has made great progress. However, our knowledge of persistent humoral immunity to SARS-CoV-2 infection is limited. The existence of protective immunity after infection will affect future transmission and disease severity. Therefore, it is important to gather knowledge about the kinetics of antibody responses. In this review, we summarize the information obtained so far on the characteristics and kinetics of the SARS-CoV-2 infection of specific humoral immune response, especially in neutralizing antibodies and their relationship with disease severity. In addition, with the emergence of variants of concern, we summarize the neutralizing effect of specific humoral immunity on variants of concern after the initial SARS-CoV-2 infection and vaccination.

X-ray triggered pea-shaped LuAG:Mn/Ca nano-scintillators and their applications for photodynamic therapy.

Photodynamic therapy (PDT) is a new minimally invasive technology for disease diagnosis and treatment. However, the biological tissue attenuation of visible light renders the depth of its penetration in tissues quite modest, which significantly restricts its therapeutic applicability. Therefore, it is an essential but yet a difficult task to enhance the X-ray sensitization impact while concurrently limiting the tissue scattering by the rational design of novel biological vectors. Herein, a novel Lu3Al5O12:Mn/Ca-Ce6@SiO2 nanoparticle system (LAMCCS) based on a pea-shaped LuAG:Mn/Ca nano-scintillator (LAMC) activating photosensitizer agent (Ce6) was designed. Due to the high radiosensitization of LAMC nano-scintillators and efficient energy conversion efficiency between LAMC and Ce6, more singlet oxygen (1O2) could be generated to efficiently damage DNA fragments and reveal a good effect of inhibiting the long-term proliferation of tumor cells in vitro. Significantly, synergistic therapy with PDT/radiotherapy (RT) and from LAMCCS nanocomposites may still maintain a high tumor growth inhibition rate of 72% than single RT of 10% in vivo. Owing to their excellent ability for X-ray sensitization and energy conversion, LAMCCS nanocomposites may have significant tumor growth suppression rates under lower X-ray dose irradiation due to their outstanding X-ray sensitization and energy conversion capabilities, which may open up a new avenue for the advancement of cancer therapy.

X-ray-Triggered CO Release Based on GdW10/MnBr(CO)5 Nanomicelles for Synergistic Radiotherapy and Gas Therapy.

Carbon monoxide (CO) therapy has become a hot topic in the field of gas therapy because of its application prospect in the treatment of various diseases. Due to the high affinity for human hemoglobin, the main challenge of CO-loaded nanomedicine is the lack of selectivity and toxicity in the delivery process. Although many commercial CO-releasing molecules (CORMs) have been widely developed because of their ability to deliver CO, CORMs still have some disadvantages, including difficult on-demand controlled CO release, poor solubility, and potential toxicity, which are limiting their further application. Herein, an X-ray-triggered CO-releasing nanomicelle system (GW/MnCO@PLGA) based on GdW10 nanoparticles (NPs) (GW) and MnBr(CO)5 (MnCO) encapsulating in the poly(lactic-co-glycolic acid) (PLGA) polymer was constructed for synergistic CO radiotherapy (RT). The production of strongly oxidative superoxide anion (O2-•) active species can lead to cell apoptosis under the X-ray sensitization of GW. Moreover, strongly oxidative O2-• radicals further oxidize and compete with the Mn center, resulting in the on-demand release of CO. The radio/gas therapy synergy to enhance the efficient tumor inhibition of the nanomicelles was investigated in vivo and in vitro. Therefore, the establishment of an X-ray-triggered controlled CO release system has great application potential for further synergistic RT CO therapy in deep tumor sites.

p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases.

Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16INK4A is deficient in the majority of HER2+ BCBMs. p16INK4A-deficiency as measured by protein immunohistochemistry predicted response to combined tucatinib and abemaciclib in orthotopic patient-derived xenografts (PDXs) of HER2 + BCBMs. Our findings establish the rationale for a biomarker-driven clinical trial of combined CDK4/6- and HER2-targeted agents for patients with HER2 + BCBM.