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Abstract Background High-grade serous ovarian cancer (HGSOC) is a common gynecologic malignancy with a poor prognosis. The traditional Chinese medicine formula Erzhimaoling decoction (EZMLD) has anticancer potential. This study aims to elucidate the anticancer effects of EZMLD on HGSOC in vitro and in vivo. Materials and methods EZMLD-containing serum was prepared from Sprague–Dawley rats for treating SKOV3 ovarian cancer cells at varying concentrations for 24 h and 48 h to determine the IC50. Concentrations of 0%, 5%, and 10% for 24 h were chosen for subsequent in vitro experiments. The roles of METTL3 and METTL14 in SKOV3 cells were explored by overexpressing these genes and combining EZMLD with METTL3/14 knockdown. Investigations focused on cell viability and apoptosis, apoptosis-related protein expression, and KRT8 mRNA m6A modification. For in vivo studies, 36 BALB/c nude mice were divided into six groups involving EZMLD (6.75, 13.5, and 27 g/kg) and METTL3 or METTL14 knockdowns, with daily EZMLD gavage for two weeks. Results In vitro, EZMLD-containing serum had IC50 values of 8.29% at 24 h and 5.95% at 48 h in SKOV3 cells. EZMLD-containing serum decreased SKOV3 cell viability and increased apoptosis. EZMLD upregulated METTL3/14 and FAS-mediated apoptosis proteins, while downregulating Keratin 8 (KRT8). EZMLD increased KRT8 mRNA m6A methylation. METTL3/14 overexpression reduced SKOV3 cell viability and increased apoptosis, while METTL3/14 knockdown mitigated EZMLD's effects. In vivo, EZMLD suppressed SKOV3 xenografts growth, causing significant apoptosis and modulating protein expression. Conclusions EZMLD has therapeutic potential for ovarian cancer and may be considered for other cancer types. Future research may explore its broader effects beyond cell apoptosis.

Abstract Background Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms. Methods A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed. Results Herein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition. Conclusion H-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI. Graphical Abstract

Cement-based materials are essential components of engineered barrier systems in geological disposal facilities for both hazardous and radioactive waste. This review provides a comprehensive examination of the application of cement-based materials in various aspects of geological disposal. Specifically, it details the use of cement paste backfill for mine tailings, which has shown a reduction in permeability by 95 %, and cementitious grouts for ground stabilization, achieving a compressive strength increase of 20 %. Shotcrete applications for rock support demonstrate enhanced adhesion properties, with a 30 % improvement in bond strength. Cementitious matrices for low- and intermediate-level waste immobilization have been optimized to reduce leachability by 40 %. Concrete containers for high-level waste and spent fuel are discussed, highlighting their ability to maintain structural integrity under high radiation and thermal loads for over 100 years. Cement-based seals for repository closure are also examined, with a focus on their self-sealing properties and long-term durability. The long-term performance of these engineered barriers is influenced by deterioration processes such as physical, chemical, and biological degradation. This review discusses optimization strategies, including the development of alternative binder systems that reduce CO₂ emissions by 30 %, the incorporation of nanoengineered cements that enhance mechanical properties by 25 %, the use of smart additives that provide real-time monitoring capabilities, and the creation of multifunctional composites that combine strength and self-healing properties. Future research directions are highlighted, emphasizing the need for advanced predictive models, innovative material formulations, and integrated monitoring technologies to ensure the long-term safety and performance of geological disposal systems.

Abstract In the global ecosystem, wetlands are vital carbon sinks, playing a crucial role in absorbing greenhouse gases such as carbon dioxide and mitigating global warming. Accurate estimation of wetland carbon content is essential for research on wetland carbon sinks. However, the carbon cycle of wetlands is complex, and the carbon sinking of wetlands is affected by climate, topography, water level conditions, vegetation types, soil types, and other factors. This has caused significant challenges in the estimation of wetland carbon sinks. In current studies, most research has focused on the impact of individual factors on wetland carbon sinks, often ignoring the interaction between various factors, which further leads to uncertainty in wetland carbon measurements. This paper aims to elucidate the process of the wetland carbon cycle, summarize the factors affecting wetland carbon sinks, and explore the interplay between various factors and their influence on wetland carbon sinks, aiming to provide theoretical support for the study of wetland carbon sinks. Additionally, this paper reviews the advantages and disadvantages of current wetland carbon measurement methods, proposes research directions for combining machine learning methods, identifies existing difficulties in current wetland carbon measurement, and offers suggestions to serve as a reference for future wetland carbon sink estimation and wetland management. Graphical Abstract

Abstract This study aimed to synchronously determine epitranscriptome-wide RNA N6-methyladenosine (m6A) modifications and mRNA expression profile in high grade serous ovarian cancer (HGSOC). The methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to comprehensively examine the m6A modification profile and the RNA-sequencing (RNA-seq) was performed to analyze the mRNA expression profile in HGSOC and normal fallopian tube (FT) tissues. Go and KEGG analyses were carried out in the enrichment of those differentially methylated and expressed genes. MeRIP-seq data showed 53,794 m6A methylated peaks related to 19,938 genes in the HGSOC group and 51,818 m6A peaks representing 19,681 genes in the FT group. RNA-seq results revealed 2321 upregulated and 2486 downregulated genes in HGSOC. Conjoint analysis of MeRIP-seq and RNA-seq data identified differentially expressed genes in which 659 were hypermethylated (330 up- and 329 down-regulated) and 897 were hypomethylated (475 up- and 422 down-regulated). Functional enrichment analysis indicated that these differentially modulated genes are involved in pathways related to cancer development. Among methylation regulators, the m6A eraser (FTO) expression was significantly lower, but the m6A readers (IGF2BP2 and IGF2BP3) were higher in HGSOC, which was validated by the subsequent real-time PCR assay. Exploration through public databases further corroborated their possible clinical application of certain methylation regulators and differentially expressed genes. For the first time, our study screens the epitranscriptome-wide m6A modification and expression profiles of their modulated genes and signaling pathways in HGSOC. Our findings provide an alternative direction in exploring the molecular mechanisms of ovarian pathogenesis and potential biomarkers in the diagnosis and predicting the prognosis of the disease.

Abstract Rare-earth-based triangular lattice materials are extremely attractive for studying unconventional magnetism. Here, we report the magnetic properties of layered CsNdSe2 based on direct current (DC) and alternating current (AC) susceptibility measurements down to 0.04 K. While the AC susceptibility at the zero DC field shows a broad hump below 0.5 K, there is no sign of any long-range magnetic ordering. Quantitative analysis of the DC magnetic susceptibility gives the negative Curie-Weiss (CW) temperature θ CW < 0 in all directions, indicating antiferromagnetic interaction between Nd ions. Of particular interest is the low temperature magnetic susceptibility, which reflects the effective spin-1/2 state with $${\theta }_{{{{{{{{\rm{cw}}}}}}}}}^{a}/{\theta }_{{{{{{{{\rm{cw}}}}}}}}}^{c}$$ θ cw a / θ cw c > 3. The estimated exchange interactions are J a /k B= 1.42 K (in-plane) and J c /k B= 0.44 K (out-of-plane), pointing to the anisotropic magnetism. First-principles calculations that include spin-orbit coupling and Coulomb correlations reveal multiple states with zero net magnetization for CsNdSe2. Both experiment and simulation strongly suggest CsNdSe2 has the spin liquid ground state with effective spin-1/2. Application of a magnetic field can induce long-range antiferromagnetic ordering with the maximum transition temperature around 0.3 K, in further support of the zero-field spin liquid state.

In this research, graphene oxide (GO) as an adsorbent was used to remove norfloxacin and ceftriaxone antibiotics from aqueous solutions. All environmental factors affecting removal (e.g., pH, adsorbent mass, contact time, and concentration) were optimized in a discontinuous system. The design of experiments and the optimization of variables were carried out using the response surface method (RSM). The results of the analysis of variance (ANOVA) and the regression coefficients of the quadratic terms indicated that the responses were significantly affected by all the studied variables (P < 0.05). Also, the quadratic polynomial model results corresponded to empirical data with a high coefficient of determination (i.e., R2 ˃ 0.99 for both antibiotics). Besides, the adjusted R2 (R2-adj ˃ 0.98 for both antibiotics) was close to R2 values, indicating a good and acceptable statistical model. According to the results, the optimal removal of antibiotics by GO occurs in conditions of pH of 8, 0.034 g of the adsorbent mass, a sonication time of 20 min, and a concentration of 25 mg L−1. In these conditions, the maximum removal efficiencies of ceftriaxone and norfloxacin were equal to 95.87% and 98.64%, respectively. GO was recovered in five adsorption/desorption processes, and the removal efficiency declined very slightly after using the adsorbent for five cycles. Therefore, it is concluded that GO is an efficient and acceptable adsorbent for removing ceftriaxone and norfloxacin from aqueous environments.

Background: The incidence of colorectal neuroendocrine tumors (NETs) is increasing, causing a social burden. At present, there is no specific prognostic model for colorectal NETs. Thus, an accurate model is needed to predict the prognosis of patients with colorectal NETs. Aim: We aimed to create a new nomogram to predict the prognosis of patients with colorectal NETs. Furthermore, we compared nomogram we established and the 8th edition of the AJCC TNM staging system in terms of prediction ability and accuracy. Methods: A total of 3353 patients with colorectal NETs were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analyses were used to assess overall survival (OS) and cancer-specific survival (CSS). Additionally, LASSO regression was used to select variables for constructing the nomogram. Furthermore, the C-index and time-dependent receiver operating characteristic (tdROC) curve were used to evaluate the nomogram. Decision curve analysis (DCA) was performed to compare the clinical utility of the nomogram with that of the TNM system. An external validation cohort (N = 61) was established to evaluate the nomogram's prediction accuracy. Results: A total of 9 factors (age, sex, marital status, tumor size, T stage, M stage, N stage, grade, and surgery) were selected based on the results of LASSO analysis. The C-indexes of the nomogram in the training and validation sets were 0.807 and 0.775, respectively, which indicated that the nomogram had better prediction accuracy than TNM staging (C-index = 0.700 in the training set and 0.652 in the validation set). The C-index of the nomogram in the external validation cohort was 0.954, indicating that the nomogram had satisfactory prediction accuracy. The results of DCA revealed that the survival nomogram possessed greater utility in clinical practice. Conclusion: We determined the OS and CSS of patients with colorectal NETs and developed a robust and clinically useful survival nomogram.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a critical innate immune pathway primarily due to its vital DNA sensing mechanism in pathogen defence. Recent research advances have shown that excessive activation or damage to the cGAS-STING pathway can exacerbate chronic inflammatory responses, playing a significant role in metabolic dysfunction and aging, leading to the development of related diseases such as obesity, osteoporosis, and neurodegenerative diseases. This article reviews the structure and biological functions of the cGAS-STING signaling pathway and discusses in detail how this pathway regulates the occurrence and development of metabolic and age-related diseases. Additionally, this article introduces potential small molecule drugs targeting cGAS and STING, aiming to provide new research perspectives for studying the pathogenesis and treatment of metabolic-related diseases.

Updates in whole genome sequencing technologies have revealed various RNA modifications in cancer, among which RNA methylation is a frequent posttranscriptional modification. RNA methylation is essential for regulating biological processes such as RNA transcription, splicing, structure, stability, and translation. Its dysfunction is strongly associated with the development of human malignancies. Research advances with respect to the regulatory role of RNA modifications in ovarian cancer include N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), and N7-methylguanosine (m7G). Numerous studies have demonstrated that epigenetic modifications of RNA can influence the progression and metastasis of ovarian cancer and may provide excellent targets for cancer therapy. This review highlights advances in research on RNA methylation modifications and ovarian cancer prognosis, carcinogenesis, and resistance, which could provide a theoretical foundation for designing therapeutic strategies for ovarian cancer based on RNA methylation modifications.

Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.

Abstract Fifty years after Anderson’s resonating valence-bond proposal, the spin-1/2 triangular-lattice Heisenberg antiferromagnet (TLHAF) remains the ultimate platform to explore highly entangled quantum spin states in proximity to magnetic order. Yb-based delafossites are ideal candidate TLHAF materials, which allow experimental access to the full range of applied in-plane magnetic fields. We perform a systematic neutron scattering study of CsYbSe2, first proving the Heisenberg character of the interactions and quantifying the second-neighbor coupling. We then measure the complex evolution of the excitation spectrum, finding extensive continuum features near the 120°-ordered state, throughout the 1/3-magnetization plateau and beyond this up to saturation. We perform cylinder matrix-product-state (MPS) calculations to obtain an unbiased numerical benchmark for the TLHAF and spectacular agreement with the experimental spectra. The measured and calculated longitudinal spectral functions reflect the role of multi-magnon bound and scattering states. These results provide valuable insight into unconventional field-induced spin excitations in frustrated quantum materials.

Abstract Haldane topological materials contain unique antiferromagnetic chains with symmetry-protected energy gaps. Such materials have potential applications in spintronics and future quantum computers. Haldane topological solids typically consist of spin-1 chains embedded in extended three-dimensional (3D) crystal structures. Here, we demonstrate that [Ni(μ−4,4′-bipyridine)(μ-oxalate)]n (NiBO) instead adopts a two-dimensional (2D) metal-organic framework (MOF) structure of Ni2+ spin-1 chains weakly linked by 4,4′-bipyridine. NiBO exhibits Haldane topological properties with a gap between the singlet ground state and the triplet excited state. The latter is split by weak axial and rhombic anisotropies. Several experimental probes, including single-crystal X-ray diffraction, variable-temperature powder neutron diffraction (VT-PND), VT inelastic neutron scattering (VT-INS), DC susceptibility and specific heat measurements, high-field electron spin resonance, and unbiased quantum Monte Carlo simulations, provide a detailed, comprehensive characterization of NiBO. Vibrational (also known as phonon) properties of NiBO have been probed by INS and density-functional theory (DFT) calculations, indicating the absence of phonons near magnetic excitations in NiBO, suppressing spin-phonon coupling. The work here demonstrates that NiBO is indeed a rare 2D-MOF Haldane topological material.

Abstract Tumor-associated lncRNAs regulated by epigenetic modification switches mediate immune escape and chemoresistance in ovarian cancer (OC). However, the underlying mechanisms and concrete targets have not been systematically elucidated. Here, we discovered that methylation modifications played a significant role in regulating immune cell infiltration and sensitizing OC to chemotherapy by modulating immune-related lncRNAs (irlncRNAs), which represent tumor immune status. Through deep analysis of the TCGA database, a prognostic risk model incorporating four methylation-related lncRNAs (mrlncRNAs) and irlncRNAs was constructed. Twenty-one mrlncRNA/irlncRNA pairs were identified that were significantly related to the overall survival (OS) of OC patients. Subsequently, we selected four lncRNAs to construct a risk signature predictive of OS and indicative of OC immune infiltration, and verified the robustness of the risk signature in an internal validation set. The risk score was an independent prognostic factor for OC prognosis, which was demonstrated via multifactorial Cox regression analysis and nomogram. Moreover, risk scores were negatively related to the expression of CD274, CTLA4, ICOS, LAG3, PDCD1, and PDCD1LG2 and negatively correlated with CD8+, CD4+, and Treg tumor-infiltrating immune cells. In addition, a high-risk score was associated with a higher IC50 value for cisplatin, which was associated with a significantly worse clinical outcome. Next, a competing endogenous RNA (ceRNA) network and a signaling pathway controlling the infiltration of CD8+ T cells were explored based on the lncRNA model, which suggested a potential therapeutic target for immunotherapy. Overall, this study constructed a prognostic model by pairing mrlncRNAs and irlncRNAs and revealed the critical role of the FTO/RP5-991G20.1/hsa-miR-1976/MEIS1 signaling pathway in regulating immune function and enhancing anticancer therapy.

The Dlk1-Dio3 domain is important for normal embryonic growth and development. The heart is the earliest developing and functioning organ of the embryo. In this study, we constructed a transcriptional termination model by inserting termination sequences and clarified that the lack of long non-coding RNA (lncRNA) expression in the Dlk1-Dio3 domain caused the death of maternal insertion mutant (MKI) and homozygous mutant (HOMO) mice starting from E13.5. Parental insertion mutants (PKI) can be born and grow normally. Macroscopically, dying MKI and HOMO embryos showed phenomena such as embryonic edema and reduced heart rate. Hematoxylin and eosin (H.E.) staining showed thinning of the myocardium in MKI and HOMO embryos. In situ hybridization (IHC) and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) showed downregulation of lncGtl2, Rian, and Mirg expression in MKI and HOMO hearts. The results of single-cell RNA sequencing (scRNA-Seq) analysis indicated that the lack of lncRNA expression in the Dlk1-Dio3 domain led to reduced proliferation of epicardial cells and may be an important cause of cardiac dysplasia. In conclusion, this study demonstrates that Dlk1-Dio3 domain lncRNAs play an integral role in ventricular development.

Aberrant accumulation of circulating follicular helper T cells (cTfh) has been found in the peripheral blood mononuclear cells (PBMCs) of Graves’ disease (GD) patients. However, the underlying mechanism that contributes to the imbalance of cTfh cells remains unknown. Previously, studies described a GD-related circular RNAs (circRNAs)-circZNF644 that might be associated with cTfh cells. This study aimed to investigate the role of circZNF644 on cTfh cells in GD patients. Here, we found that circZNF644 was highly stable expression in the PBMCs of GD patients, which was positively correlated with the serum levels of TSH receptor autoantibodies (TRAb). Knockdown of circZNF644 caused a reduction of the proportion of cTfh cells in vitro. Mechanistically, circZNF644 served as a ceRNA for miR-29a-3p to promote ICOS expression, resulting in increased cTfh cells. In the PBMCs of GD patients, circZNF644 expression was positively correlated with ICOS expression and the percentage of cTfh cells, but negatively related to miR-29a-3p expression. Additionally, a strong relationship between circZNF644 and IL-21 was revealed in GD patients, and silencing of circZNF644 inhibited IL-21 expression. Our study elucidated that elevated expression of circZNF644 is a key feature in the development of GD and may contribute to the pathogenic role of cTfh cells in GD.

Abstract The notion that phonons can carry pseudo‐angular momentum has many major consequences, including topologically protected phonon chirality, Berry curvature of phonon band structure, and the phonon Hall effect. When a phonon is resonantly coupled to an orbital state split by its crystal field environment, a so‐called vibronic bound state forms. Here, a vibronic bound state is observed in NaYbSe2, a quantum spin liquid candidate. In addition, field and polarization dependent Raman microscopy is used to probe an angular momentum transfer of ΔJz = ±ℏ between phonons and the crystalline electric field mediated by the vibronic bound stat. This angular momentum transfer between electronic and lattice subsystems provides new pathways for selective optical addressability of phononic angular momentum via electronic ancillary states.

This paper aims to study the crashworthiness of shrink tubes for rail vehicles under axial impact loading. A theoretical model of shrink tube for platform force prediction under interference fit conditions was proposed. The trolley crash test was used to experimentally study the structural energy absorption and characteristics during collision, and a corresponding finite element model was constructed and validated. The finite element model validated the accuracy of the theoretical model. The influence of structural parameters on the crashworthiness of shrink tube under interference conditions was then studied. Structural design variables, including the magnitude of interference (int_pre), thickness (T), long right-angle edge (tri_x) and short right-angle edge (tri_z) were sampled using a full factorial and a Latin hypercube design method. Based on the above samples, the moving least squares method (MLSM) was used to construct an approximate model of peak force (Fmax), specific energy absorption (SEA), and platform force (Fplt). The main effects analysis illustrated that the tri_z had the most significant effects on the peak force, specific energy absorption and platform force. To minimize Fmax and maximize SEA, the global response surface method (GRSM) was employed for parameter optimization. Finally, the optimized configurations were obtained with int_pre=0.067mm, T=10.003mm, tri_x=21.485mm, and tri_z=6.101mm. Compared to the initial design, the SEA value was increased by 16.41 %, while the Fmax value was decreased by 2.21%. The error of platform force derived from the optimal solution and theoretical prediction was 3.62%, which verified that the theoretical prediction model was credible within an acceptable range.

Biologically active and nanoscale extracellular vesicles (EVs) participate in a variety of cellular physiological and pathological processes in a cell-free manner. Unlike cells, EVs not only do not cause acute immune rejection, but are much smaller and have a low risk of tumorigenicity or embolization. Because of their unique advantages, EVs show promise in applications in the diagnosis and treatment of reproductive disorders. As research broadens, engineering strategies for EVs have been developed, and engineering strategies for EVs have substantially improved their application potential while circumventing the defects of natural EVs, driving EVs toward clinical applications. In this paper, we will review the engineering strategies of EVs, as well as their regulatory effects and mechanisms on reproductive disorders (including premature ovarian insufficiency (POI), polycystic ovarian syndrome (PCOS), recurrent spontaneous abortion (RSA), intrauterine adhesion (IUA), and endometriosis (EMS)) and their application prospects. This work provides new ideas for the treatment of female reproductive disorders by engineering EVs.

Objective: To extract polyphenols in Dendrobium nobilis flower (DNF) through a green process method and to evaluate its antioxidant activity in vitro. Methods: Using PEG 200 as solvent, the single factors tests and response surface experiments were conducted to optimize the extraction conditions on the yield of polyphenols from DNF. AB-8 macroporous resin adsorption technology was applied for the enrichment of the above polyphenols and the recycling of PEG 200. The ABTS and DPPH assays were performed to investigate the antioxidant properties of those polyphenols. Results: The optimal parameters were as follows: The solvent volume fraction was 55%, the liquid-solid ratio was 38:1 mL·g−1, the ultrasonic time was 99 min, the ultrasonic temperature was 80 ℃. The polyphenols yield could reached up to 338.88 mg·g−1 in these conditions. Within the test concentration range, the antioxidant capacity in vitro of those polyphenols was similar to that of ascorbic acid. The IC50 of ABTS and IC50 of DPPH free radicals of the polyphenols were 4.486 and 2.792 mg·mL−1 respectively. Conclusion: The green solvent PEG 200 can be used for the extraction of polyphenols from Dendrobium nobilis flower and can be reused; the in vitro antioxidant capacity of the extracted polyphenols is strong, which has good prospects for development and application.

Abstract Background Acute thoracic aortic dissection (ATAD) is a fatal condition characterized by tear of intima, formation of false lumen and rupture of aorta. However, the subpopulations of normal and dissected aorta remain less studied. Methods Single-cell RNA sequencing was performed including 5 patients with ATAD and 4 healthy controls. Immunohistochemistry and immunofluorescence were used to verify the findings. Results We got 8 cell types from human ascending aorta and identified 50 subpopulations including vascular smooth muscle cells (VSMCs), endothelial cells, fibroblasts, neutrophils, monocytes and macrophages. Six transmembrane epithelial antigen of prostate 4 metalloreductase (STEAP4) was identified as a new marker of synthetic VSMCs. CytoTRACE identified subpopulations with higher differentiation potential in specified cell types including synthetic VSMCs, enolase 1+ fibroblasts and myeloid-derived neutrophils. Synthetic VSMCs-derived C-X-C motif chemokine ligand 12 (CXCL12) might interact with neutrophils and fibroblasts via C-X-C motif chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), respectively, which might recruit neutrophils and induce transdifferentitation of fibroblasts into synthetic VSMCs. Conclusion We characterized signatures of different cell types in normal and dissected human ascending aorta and identified a new marker for isolation of synthetic VSMCs. Moreover, we proposed a potential mechanism that synthetic VSMCs might interact with neutrophils and fibroblasts via CXCL12-CXCR4/ACKR3 axis whereby deteriorating the progression of ATAD, which might provide new insights to better understand the development and progression of ATAD.

Tumor development is closely associated with a complex tumor microenvironment, which is composed of tumor cells, blood vessels, tumor stromal cells, infiltrating immune cells, and associated effector molecules. T helper type 17 (Th17) cells, which are a subset of CD4+ T cells and are renowned for their ability to combat bacterial and fungal infections and mediate inflammatory responses, exhibit context-dependent effector functions. Within the tumor microenvironment, different molecular signals regulate the proliferation, differentiation, metabolic reprogramming, and phenotypic conversion of Th17 cells. Consequently, Th17 cells exert dual effects on tumor progression and can promote or inhibit tumor growth. This review aimed to investigate the impact of various alterations in the tumor microenvironment on the antitumor and protumor effects of Th17 cells to provide valuable clues for the exploration of additional tumor immunotherapy strategies.

En este estudio se utilizó un nuevo tipo de floculante microbiano combinado con coagulante de cloruro férrico de polialuminio (PAFC) en el experimento de coagulación-floculación de agua de limo de carbón. Se investigaron los efectos de la dosis de PAFC, la dosis de biofloculante y el pH sobre la turbidez y la demanda química de oxígeno (COD) del agua de limo de carbón. Los resultados mostraron que las mejores condiciones para eliminar la turbidez del agua de limo y la COD mediante la prueba de factor único fueron las siguientes: la dosis de PAFC fue de 37.5 mg/l, la dosis de biofloculante fue de 0.75 mg/l y el pH fue de 7.0. A través de la prueba ortogonal se identificó que los factores más influyentes para la turbidez y eliminación de COD son el pH y la dosis de PAFC, respectivamente. La mejor condición de la coagulación-floculación fue con una dosis de PAFC de 50.0 mg/l, una dosis de biofloculante de 0.5 mg/l y el pH de 7.0. Bajo esta condición, se obtuvo una eficiencia de remoción de turbidez del 93.2 % y una eficiencia de remoción de COD del 47.2 %.

BackgroundEarly diagnosis of esophageal squamous cell carcinoma (ESCC) is critical for effective treatment and optimal prognosis; however, less study on serum biomarkers for the early ESCC detection has been reported. The aim of this study was to identify and evaluate several serum autoantibody biomarkers in early ESCC.MethodsWe initially screened candidate tumor-associated autoantibodies (TAAbs) associated with ESCC by serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (nano-LC-Q-TOF-MS/MS), and the TAAbs were further subjected to analysis by Enzyme-linked immunosorbent assay (ELISA) in a clinical cohort (386 participants, including 161 patients with ESCC, 49 patients with high-grade intraepithelial neoplasia [HGIN] and 176 healthy controls [HC]). Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance.ResultsThe serum levels of CETN2 and POFUT1 autoantibodies which were identified by SERPA were statistically different between ESCC or HGIN patients and HC in ELISA analysis with the area under the curve (AUC) values of 0.709 (95%CI: 0.654-0.764) and 0.741 (95%CI: 0.689-0.793), 0.717 (95%CI: 0.634-0.800) and 0.703 (95%CI: 0.627-0.779) for detection of ESCC and HGIN, respectively. Combining these two markers, the AUCs were 0.781 (95%CI: 0.733-0.829), 0.754 (95%CI: 0.694-0.814) and 0.756 (95%CI: 0.686-0.827) when distinguishing ESCC, early ESCC and HGIN from HC, respectively. Meanwhile, the expression of CETN2 and POFUT1 was found to be correlated with ESCC progression.ConclusionsOur data suggest that CETN2 and POFUT1 autoantibodies have potential diagnostic value for ESCC and HGIN, which may provide novel insights for early ESCC and precancerous lesions detection.

ObjectiveTo compare the effects of five hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs), two erythropoiesis-stimulating agents (ESAs), and placebo on iron metabolism in renal anemia patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).MethodFive electronic databases were searched for studies. Randomized controlled clinical trials comparing HIF-PHIs, ESAs, and placebo in NDD-CKD patients were selected. The statistical program used for network meta-analysis was Stata/SE 15.1. The main outcomes were the change in hepcidin and hemoglobin (Hb) levels. The merits of intervention measures were predicted by the surface under the cumulative ranking curve method.ResultsOf 1,589 original titles screened, data were extracted from 15 trials (3,228 participants). All HIF-PHIs and ESAs showed greater Hb level–raising ability than placebo. Among them, desidustat demonstrated the highest probability of increasing Hb (95.6%). Hepcidin [mean deviation (MD) = -43.42, 95%CI: -47.08 to -39.76], ferritin (MD= -48.56, 95%CI: -55.21 to -41.96), and transferrin saturation (MD = -4.73, 95%CI: -5.52 to -3.94) were decreased, while transferrin (MD = 0.09, 95%CI: 0.01 to 0.18) and total iron-binding capacity (MD = 6.34, 95%CI: 5.71 to 6.96) was increased in HIF-PHIs versus those in ESAs. In addition, this study observed heterogeneity in the ability of HIF-PHIs to decrease hepcidin. Compared with darbepoetin, only daprodustat (MD = –49.09, 95% CI: –98.13 to –0.05) could significantly reduce hepcidin levels. Meanwhile, daprodustat also showed the highest hepcidin-lowering efficacy (84.0%), while placebo was the lowest (8.2%).ConclusionFor NDD-CKD patients, HIF-PHIs could ameliorate functional iron deficiency by promoting iron transport and utilization, which may be achieved by decreasing hepcidin levels. Interestingly, HIF-PHIs had heterogeneous effects on iron metabolism.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242777, Identifier CRD42021242777.

Two-dimensional electron gas (2DEG) at the (100) KTaO3(KTO) surface and interfaces has attracted extensive interest because of its abundant physical properties. Here, light illumination-induced semiconductor–metal transition in the 2DEG at the KTO surface was investigated. 2DEG was formed at the surface of KTO by argon ion bombardment. The 2DEG prepared with a shorter bombardment time (300 s) exhibits semiconducting behavior in the range of 20~300 K in the dark. However, it shows a different resistance behavior, namely, a metallic state above ~55 K and a semiconducting state below ~55 K when exposed to visible light (405 nm) with a giant conductivity increase of about eight orders of magnitude at 20 K. The suppression of the semiconducting behavior is found to be more pronounced with increasing light power. After removing the illumination, the resistance cannot recover quickly, exhibiting persistent photoconductivity. More interestingly, the photoresponse of the 2DEG below 50 K was almost independent of the laser wavelength, although the photon energy is lower than the band gap of KTO. The present results provide experimental support for tuning oxide 2DEG by photoexcitation, suggesting promising applications of KTO-based 2DEG in future electronic and optoelectronic devices.

An increasing number of researchers are interested in studying CsPbBr3 perovskite solar cells (PSCs) due to their high stability. However, the use of methanol during the spin-coating process is extremely hazardous, both to humans and the environment. CsBr is very soluble in water, but owing to its high specific heat capacity, water causes uneven crystallization and the creation of pores, which negatively impact the performance of CsPbBr3 devices. In this paper, water is introduced as the solvent for CsBr in place of methanol to prepare CsPbBr3 films and ethanol is used as the surface treatment solvent. The morphology and crystal quality of CsPbBr3 films are improved by varying the concentration and spin-coating cycles of the CsBr/H2O solution and adding ethanol post-treatment. The results show that high-quality CsPbBr3 films with reduced grain boundaries and high phase-purity were obtained by spin-coating 100 mg/mL CsBr/H2O solution three times and using ethanol as a post-treatment. The CsPbBr3 solar cells yielded a maximum efficiency of 7.65% and demonstrate long-term stability over 1100 h.

Abstract Background Delayed bleeding is an important adverse event after gastric endoscopic submucosal dissection (ESD). We aimed to externally validate the Bleeding after ESD Trend from Japan (BEST-J) score and subsequently develop a risk prediction model for bleeding in Chinese patients with early gastric cancer (EGC) after ESD. Methods The clinical data of patients who underwent ESD for EGC in Beijing Friendship Hospital from June 2013 to December 2019 were collected retrospectively. The BEST-J score was evaluated according to the clinical data. Through univariate and multivariate logistic regression analyses of the clinical data, the factors affecting delayed bleeding were identified, and a new risk prediction model for bleeding was established. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the two prediction models. Results A total of 444 patients with EGC undergoing ESD were included, of whom 27 patients had delayed bleeding (6.1%). Multivariate logistic regression analysis showed that a history of smoking (P = 0.029), tumor size > 20 mm (P = 0.022), intraoperative use of hemoclips (P = 0.025), resection of multiple tumors (P = 0.027), and prolongation of activated partial thromboplastin time (APTT) (P = 0.020) were independent influencing factors for delayed bleeding. ROC curve analysis showed that the areas under the curves (AUCs) were different between the BEST-J score and the newly built prediction model (0.624 vs. 0.749, P = 0.012). Conclusions The BEST-J score has moderately good discrimination for Chinese patients with EGC. However, for patients with EGC without severe comorbidities, the new risk prediction model may predict delayed bleeding better than the BEST-J score.

Abstract Chemoresistance is a severe outcome among patients with epithelial ovarian cancer (EOC) that leads to a poor prognosis. YBX-1 has been shown to cause treatment failure and cancer progression in EOC. However, strategies that directly target YBX-1 are not yet conceivable. Here, we identified that SIAH1 which was downregulated in chemoresistant EOC samples and cell lines functioned as novel E3 ligases to trigger degradation of YBX-1 at cytoplasm by RING finger domain. Mechanistic studies show that YBX-1 was ubiquitinated by SIAH1 at lys304 that lead to the instability of its target m5C-modified mRNAs, thus sensitized EOC cells to cDDP. Overexpression of SIAH1 enhanced the antitumor efficacy of cisplatin in vitro and in vivo, which were partially impaired by ectopic expression of YBX-1 or depletion of YBX-1 ubiquitination. In summary, our data identify the SIAH1/YBX-1 interaction as a therapeutic target for overcoming EOC chemoresistance.

ObjectivesThe feasibility of utilizing 4% sodium citrate as an alternative locking solution for central venous catheters (CVCs) (excluding dialysis catheters) was assessed.MethodsUsing heparin saline and 4% sodium citrate as locking solution, then 152 patients in ICU undergoing infusion with central venous catheters, were randomly assigned to receive either 10 U/mL heparin saline or 4% sodium citrate. The used outcome indicators include: four indexes of blood coagulation at 10 minutes after locking and 7 d after the first locking, bleeding around the puncture site and subcutaneous hematoma rate, gastrointestinal bleeding rate, catheter indwelling time, catheter occlusion rate, catheter-related bloodstream infection (CRBSI) rate, rate of ionized calcium < 1.0 mmol/L. The main outcome indicator was the activated partial thromboplastin time (APTT) at 10 min after tube locking. The trial was approved by relevant authorities (Chinese Clinical Trial Registry, no: ChiCTR2200056615, registered on February 9, 2022, http://www.chictr.org.cn; Ethics Committee of People's Hospital of Zhongjiang County, no: JLS-2021-034, approved at May 10, 2021, and no: JLS-2022-027, approved at May 30, 2022).ResultsAmong the main outcome measures, the heparin group showed a significant increase in APTT compared to the sodium citrate group at 10 min after locking (LSMD = 8.15, 95%Cl 7.1 to 9.2, P < 0.001). Among the secondary outcome measures, the heparin group demonstrated a significant increase in prothrombin time (PT) compared to the sodium citrate group at 10 minutes after locking (LSMD = 0.86, 95%CI 0.12 to 1.61, P = 0.024). It is found that APTT (LSMD = 8.05, 95%CI 6.71 to 9.4, P < 0.001), PT (LSMD = 0.78, 95%CI 0.14 to 1.42, P = 0.017) and fibrinogen (FB) (LSMD = 1.15, 95%CI 0.23 to 2.08, P = 0.014) at 7 d after locking are increased in the heparin group compared to sodium citrate group. There was no significant difference in catheter indwelling time between the two groups (P = 0.456). The incidence of catheter blockage was lower in sodium citrate group (RR = 0.36, 95%CI 0.15 to 0.87, P = 0.024). No CRBSI occurred in the two groups. Among the safety evaluation indexes, the incidence of bleeding around the puncture site and subcutaneous hematoma was lower in sodium citrate group (RR = 0.1, 95%CI 0.01 to 0.77, P = 0.027). There was no significant difference in the incidence of calcium ion < 1.0 mmol/L between the two groups (P = 0.333).ConclusionsIn ICU patients using CVCs (excluding dialysis catheters) infusion, employing 4% sodium citrate as a locking liquid can reduce the risk of bleeding and catheter occlusion without any hypocalcemia.

In order to understand the distribution characteristics of heavy metal elements in the soil of the coal mine reclamation area and its impact on the surrounding environment and provide technical support for the selection of a reasonable method for the coal mine land reclamation, taking the soil of the Shanxi coal mine reclamation area as the research object, the distribution characteristics of four heavy metal elements in the soil of two different reclamation methods in deep and shallow coal mines were studied by the continuous extraction method. The research results show that the content of heavy metals in the deep reclamation area is significantly higher than that in the unreclaimed area, and the content of Zn and Cr is 6.23 times and 1.57 times that of the unreclaimed area, respectively. The content of heavy metal Zn is nine times more than the national standard value. Soils in deep reclamation areas have been contaminated with Zn and Cr. The heavy metal content in the shallow reclamation area is higher than that in the unreclaimed area but lower than the national standard value. Pb in the coal mine reclamation area has a high pollution impact on the surrounding soil. Although the content of Zn in the soil is relatively large, due to the stable nature of the residue, it has little impact on the environment. Heavy metals Ni and Cr are dangerous to the surrounding soil under certain conditions; the RSP value of the heavy metal Pb in the soil of the deep and shallow reclamation areas is the largest, which has the greatest impact on the environment, and the other three heavy metals have no pollution. Pb in coal mines has a serious impact on the environment.

The energy storage plays an important role in the operation safety of the microgrid system. Appropriate capacity configuration of energy storage can improve the economy, safety, and renewable energy utilization of the microgrid. This study considers the uncertainty of renewable energy, and builds an energy storage capacity configuration (ESCC) in microgrid by using the distributionally robust optimization (DRO). This model co-optimizes energy storage planning, day-ahead scheduling, and renewable energy utilization of the microgrid, which derives the energy storage configuration strategy, balancing renewable energy utilization and operation economics of microgrid. The proposed model is a two-stage model with distributionally robust chance constrains. By applying decision rules, variable substitution, and duality techniques, this model is approximately transformed into a mixed integer programming problem with a second-order cone constraint, which can be directly solved. Experiments on the IEEE 33-bus system are carried out to verify the effectiveness and advantages of the proposed model.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is defined by the accumulation of triglycerides (TG). The body mass index (BMI) is associated with NAFLD. This large-scale cohort study was performed to evaluate and quantify the mediating effect of TG on the association between BMI and NAFLD. Methods: In total, 15,943 participants in the Kailuan Group were recruited between 2010 and 2014. The impact of TG on the association between BMI and NAFLD was determined through a mediation analysis. Results: BMI was an independent risk factor for incident NAFLD, with OR of 1.416 (95% CI 1.338–1.499) and 1.187 (95% CI 1.137–1.240) in the low-BMI and high-BMI groups, respectively (p < 0.001). The TG level was a risk factor for NAFLD in the high-BMI group, with an OR of 2.775 (95% CI 1.488–5.177; p = 0.001). Positive associations between BMI and the TG level remained in the 2 above mentioned groups after adjusting for confounders (β = 0.072 and 0.032; p < 0.001). The mediation analysis revealed that TG contributed to 26.050% of incident NAFLD in the high-BMI group (p = 0.01). Conclusion: A high BMI was an independent risk factor for incident NAFLD, and a high TG level was a risk factor in the high-BMI group (BMI ≥24). TG contributes about 25% to incident NAFLD in people with obesity.

Circular RNAs (circRNAs) are important transcriptional regulators of genome expression that participate in the pathogenesis of human diseases. Mechanistically, circRNAs, as competitive endogenous RNAs (ceRNAs), can sponge microRNAs (miRNAs) with miRNA response elements. A previous study identified that hsa_circ_0089172 (circNUP214) is abnormally expressed in Hashimoto’s thyroiditis. However, the role of circNUP214 in rheumatoid arthritis (RA) remains unclear. In total, 28 RA patients and 28 healthy controls were enrolled in this study. We found that circNUP214 is an abundant and stable circRNA in RA patients that can potentially differentiate RA patients from healthy subjects. Additionally, the elevated levels of IL-23R positively correlated with circNUP214 expression. The knockdown of circNUP214 resulted in the reduction of IL-23R at both transcriptional and translational levels in human CD4+ T cells. The proportion of circulating Th17 cells and the transcript levels of IL-17A were increased in RA patients and were both positively correlated with IL-23R expression. Moreover, positive correlations between the transcript levels of circNUP214 and the percentage of Th17 cells and the transcript levels of IL-17A were observed in RA patients. The downregulation of circNUP214 decreased the proportion of Th17 cells and the transcript levels of IL-17A in vitro. Furthermore, circNUP214 functioned as a ceRNA for miR-125a-3p in RA patients. Taken together, our results indicate that elevated levels of circNUP214 contribute to the Th17 cell response in RA patients.

IntroductionAlthough child and adolescent health is the core of the global health agenda, the cause of death and its expected contribution to life expectancy (LE) among those aged 5–14 are under-researched across countries, especially in low- and middle-income countries (LMICs).MethodsDeath rates per 10 years age group including a 5–14-year-old group were calculated by the formula, which used the population and the number of deaths segmented by the cause of death and gender from the 2019 Global Burden of Disease (GBD) study. LE and cause-eliminated LE in 10-year intervals were calculated by using life tables.ResultsIn 2019, the global mortality rate for children and adolescents aged 5–14 years was 0.522 (0.476–0.575) per 1,000, and its LF was 71.377 years. In different-income regions, considerable heterogeneity remains in the ranking of cause of death aged 5–14 years. The top three causes of death in low-income countries (LICs) are enteric infections [0.141 (0.098–0.201) per 1,000], other infectious diseases [0.103 (0.073–0.148) per 1,000], and neglected tropical diseases and malaria [0.102 (0.054–0.172) per 1,000]. Eliminating these mortality rates can increase the life expectancy of the 5–14 age group by 0.085, 0.062, and 0.061 years, respectively. The top three causes of death in upper-middle income countries (upper MICs) are unintentional injuries [0.066 (0.061–0.072) per 1,000], neoplasm [0.046 (0.041–0.050) per 1,000], and transport injuries [0.045 (0.041–0.049) per 1,000]. Eliminating these mortality rates can increase the life expectancy of the 5–14 age group by 0.045, 0.031, and 0.030 years, respectively.ConclusionThe mortality rate for children and adolescents aged 5–14 years among LMICs remains high. Considerable heterogeneity was observed in the main causes of death among regions. According to the main causes of death at 5–14 years old in different regions and countries at different economic levels, governments should put their priority in tailoring their own strategies to decrease preventable mortality.

The increase of wind generation (WG) has challenged the conventional way of probabilistic load flow (PLF) calculation. A reliable and efficient PLF method is required to face the stochastic nature of various power systems with WG. Firstly, the paper analyzes several typical cumulant methods (CMs) for PLF, such as Gram-Charlier expansion of type A (GCA), Gram-Charlier expansion of type C (GCC), and maximum entropy (ME). Then, an improved integrated CM by probability distribution pre-identification is proposed for power systems with WG based on doubly fed induction generations (DFIGs). The skewness and kurtosis are used as probability distribution pre-identification indices in the CM framework. Meanwhile, the influence of the DFIG control strategy on reactive power is considered in the load flow model and the moment calculation. Finally, the accuracy and efficiency of the proposed method are validated with the IEEE test system. In various scenarios, suitable CM is selected and applied to the PLF based on pre-identifying distribution characteristics. Results reveal that probabilistic density functions (PDFs) of bus voltages and line flows obtained by the proposed method have both accuracy and efficiency.

The performance of potassium sodium niobate ((K, Na) NbO3, KNN)-based lead-free piezoelectric ceramics has significantly improved over the past decade. However, the performance bottlenecks of KNN-based ceramics cannot be ignored. Here, the Nb2O5 precursor is obtained after thermal pretreatment, which can evidently improve the piezoelectric properties and strain temperature stability of KNN-based ceramics. With the help of the Nb2O5 precursor treated at 800 °C, the optimal piezoelectric constant d33 of 303 pC/N, inverse piezoelectric constant d*33 of 378 pm/V, Curie temperature TC of 310 °C and electromechanical coupling factor kp of 42% are obtained, and the value of d33 improves by about 30% compared with that of the ceramic prepared with untreated Nb2O5 as raw material. Additionally, in comparison with the strain temperature stability of the ceramics prepared with untreated Nb2O5 as raw material, the temperature stability is enhanced. Therefore, this study provides a useful approach to break the existing performance bottleneck and further improve the properties of KNN-based ceramics.

The BiAlO3 (BA) and (Bi0.5Na0.5)ZrO3 (BNZ) are selected to form a solid solution with (K0.48Na0.52)NbO3 via traditional solid state technique to optimize the electrical performance and temperature stability of KNN-based lead-free ceramics, simultaneously. Here we show that doped BA has a great influence on phase structure, morphologies, and electrical properties. The XRD patterns and dielectric constant versus temperature curves reveal that an increase in the BA content results in a transform of phase structures from a coexistence state of rhombohedral, orthorhombic and tetragonal phases to pseudocubic phase. Owing to the construction of R-O-T phase boundary, optimized performances (TC ∼ 336 °C, d33 ∼ 306 pC/N, kp = 0.48) are obtained in 0.962(K0.48Na0.52)NbO3-0.003BiAlO3-0.035(Bi0.5Na0.5)ZrO3 (KNN-3) ceramics. Based on the sintered KNN-3 ceramic samples, high-frequency ultrasound imaging transducers are designed and fabricated, which exhibits a high center frequency of 24.5 MHz, a broad −6 dB bandwidth of 97% and a high-sensitivity. Finally, the imaging characteristic of the lead-free transducers is demonstrated via ex vivo imaging of biological tissue structure. As environment friendly materials, the excellent electrical and acoustic performance of developed KNN-based ceramics has great potential for practical applications.

Background. Graves’ disease (GD) is one of the most common autoimmune diseases worldwide and develops in 20 to 50 cases per 100,000 persons annually. Long noncoding RNAs (lncRNAs) are widely expressed in multiple human diseases and have pivotal functions in gene regulation. This study is aimed at determining the lncRNA profile in peripheral blood mononuclear cells (PBMCs) from GD patients and investigating the role of ENST00000604491 in GD. Methods. A total of 31 GD patients and 32 normal controls were enrolled in the study. Next-generation sequencing was performed to identify the dysregulated lncRNAs in the PBMCs from the 5 GD patients and 5 normal controls, and 26 GD patients and 27 controls were used to verify the selected lncRNAs. The relative expression of verified lncRNAs, forkhead box P1 (FOXP1), and IKAROS family zinc finger 3 (IKZF3) from these samples was detected by quantitative real-time PCR. The potential biomarker value was assessed by using receiver operating characteristic (ROC) curve analysis. Results. A total of 37,683 dysregulated expressed lncRNAs were indicated, of which 5 lncRNAs were significantly upregulated and 83 lncRNAs were remarkably downregulated in the GD patients compared with healthy subjects. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that abnormally expressed lncRNAs were mainly enriched in immune system-related signalling pathways. Among the selected lncRNAs, the relative expression of ENST00000604491 was significantly downregulated and negatively correlated with the serum levels of thyroid-stimulating hormone receptor antibodies (TRAb) in GD patients. Further studies confirmed that decreased FOXP1 expression was inversely correlated with serum TRAb levels in GD patients. Moreover, there was a notably positive correlation between ENST00000604491 expression and FOXP1 transcript levels in GD. The area under the ROC curve of ENST00000604491 was up to 0.74 (95% confidence interval: 0.60-0.87, p

Abstract Background Naphthoquine (NQ) is a suitable partner anti-malarial for the artemisinin-based combination therapy (ACT), which is recommended to be taken orally as a single-dose regimen. The metabolism of NQ was mainly mediated by CYP2D6, which is well-known to show gender-specific differences in its expression. In spite of its clinical use, there is limited information on the pharmacokinetics of NQ, and no data are available for females. In this study, the effect of gender on the pharmacokinetics and antiplasmodial efficacy of NQ in rodents was evaluated. The underlying factors leading to the potential gender difference, i.e., plasma protein binding and metabolic clearance, were also evaluated. Methods The pharmacokinetic profiles of NQ were investigated in healthy male or female rats after a single oral administration of NQ. The antiplasmodial efficacy of NQ was studied in male or female mice infected with Plasmodium yoelii. The recrudescence and survival time of infected mice were also recorded after drug treatment. Plasma protein binding of NQ was determined in pooled plasma collected from male or female mice, rat or human. In vitro metabolism experiments were performed in the liver microsomes of male or female mice, rat or human. Results The results showed that the gender of rats did not affect NQ exposure (AUC0–t and Cmax) significantly (P > 0.05). However, a significant (P 0.05) antiplasmodial activity was found for NQ in male mice (ED90, 1.10 mg/kg) infected with P. yoelii, compared with female mice (ED90, 1.67 mg/kg). The binding rates of NQ to plasma protein were similar in males and females. There was no metabolic difference for NQ in male and female mice, rat or human liver microsomes. Conclusions These results indicated that the pharmacokinetic profiles of NQ were similar between male and female rats, except for a longer t1/2 in male rats. The difference was not associated with plasma protein binding or hepatic metabolic clearance. Equivalent antiplasmodial activity was found for NQ in male and female mice infected with P. yoelii. This study will be helpful for the rational design of clinical trials for NQ.

In this work, we present a new piezoelectric solid solution consisting of two typical alkali niobate-based materials, K0.5Na0.5NbO3 (KNN) and Li0.15Na0.85NbO3 (LNN). Although KNN and LNN have the same perovskite structure, they exhibit extremely different electrical properties and mechanical behaviors. The phase structures, electrical and mechanical evolutions of the new lead-free piezoelectric materials with different ratios of KNN and LNN are comprehensively and theoretically investigated. According to the X-ray diffraction patterns and curves of permittivity versus temperature, a series of complicated phase transitions can be found with varied LNN content. Rietveld refinement results based on XRD patterns reveal an oxygen octahedron tilting in the LNN-rich crystal structure, and simultaneously the reasons for octahedron tilting are discussed. The distorted crystal structure is accompanied by extremely decreased electric properties but increased mechanical properties, which reveals electrical and mechanical properties of alkali niobate-based piezoelectric ceramics strongly depend on their inner structures, and the enhancement of intrinsic hardness results in the deterioration of piezoelectric properties. Our work exhibits the detailed evolutions of structure, electrical and mechanical properties from KNN to LNN, which provides experimental and theoretical basis for development of new alkali niobate-based piezoelectric materials. Keywords: Lead-free, Piezoelectric ceramics, Crystal structure, Electrical properties, Mechanical behaviors

The quantum spin liquid (QSL) state in rare-earth triangular lattices has attracted much attention recently due to its potential application in quantum computing and communication. Here, we report the single-crystal growth synthesis, crystal structure characterizations, and magnetic properties of AYbSe2 (A = K and Rb) compounds. The x-ray diffraction analysis shows that AYbSe2 (A = K and Rb) crystallizes in a trigonal space group, R-3m (No. 166) with Z = 3. AYbSe2 possesses a two-dimensional (2D) Yb–Se–Yb layered structure formed by edged-shared YbSe6 octahedra. The magnetic properties are highly anisotropic for both title compounds, and no long-range order is found down to 0.4 K, revealing the possible QSL ground state in these compounds. The isothermal magnetization exhibits a one-third magnetization plateau when the magnetic fields are applied in the ab-plane. Heat capacity is performed along both ab-plane and c axis and features the characteristic dome for triangular magnetic lattice compounds as a function of magnetic fields. Due to the change in the interlayer and intralayer distance of Yb3+, the dome shifts to low fields from KYbSe2 to RbYbSe2. All these results indicate that the AYbSe2 family presents unique frustrated magnetism close to the possible QSL and noncollinear spin states.

Luminal breast cancer (BC) accounts for a large proportion of patients in BC, with high heterogeneity. Determining the precise subtype and optimal selection of treatment options for luminal BC is a challenge. In this study, we proposed an MSBR framework that integrate DNA methylation profiles and transcriptomes to identify immune subgroups of luminal BC. MSBR was implemented both on a key module scoring algorithm and “Boruta” feature selection method by DNA methylation. Luminal A was divided into two subgroups and luminal B was divided into three subgroups using the MSBR. Furthermore, these subgroups were defined as different immune subgroups in luminal A and B respectively. The subgroups showed significant differences in DNA methylation levels, immune microenvironment (immune cell infiltration, immune checkpoint PD1/PD-L1 expression, immune cell cracking activity (CYT)) and pathology features (texture, eccentricity, intensity and tumor-infiltrating lymphocytes (TILs)). The results also showed that there is a subgroup in both luminal A and B that has the benefit from immunotherapy. This study proposed a classification of luminal BC from the perspective of epigenetics and immune characteristics, which provided individualized treatment decisions.

Lead-free, bismuth-based perovskite solar cells (PSCs) are promising, non-toxic, and stable alternatives to lead-based PSCs, which are environmentally harmful and highly unstable under deprived air conditions. However, bismuth-based PSCs still suffer from low-power-conversion efficiency (PCE) due to their large bandgap and poor film morphology. Their poor film-forming ability is the greatest obstacle to Cs₃Bi₂I₉ progress in thin-film solar cell technology. This study synthesizes novel, lead-free perovskites with a small bandgap, excellent stability, and highly improved photovoltaic performance by integrating different amounts of potassium iodide (KI) into a perovskite precursor solution. KI incorporation improves the crystallinity of the perovskite, increases the grain size, and decreases the potential contact distribution, which is demonstrated by X-ray diffraction, electronic scanning microscopy, atomic force microscopy, and ultraviolet-visible spectroscopy. The Cs₃Bi₂I₉ PSC device with 2 vol. % incorporation of KI shows the highest PCE of 2.81% and Voc of 1.01 V as far as all the Bi-based cells fabricated for this study are concerned. The study demonstrates that incorporating KI in the Cs₃Bi₂I₉ perovskite layer highly stabilizes the resultant PSC device against humidity to the extent that it maintains 98% of the initial PCE after 90 days, which is suitable for solar cell applications. The devices also demonstrate greater resistance to airborne contaminants and high temperatures without encapsulation, opening up new possibilities for lead-free Cs₃Bi₂I₉ PSCs in future commercialization.

For CsPbBr3 perovskite materials, it is especially important to reduce interface defects, suppress non-radiative recombination, and improve morphology to achieve highly efficient and stable CsPbBr3 perovskite solar cells (PSCs). Herein, we reported a facile but highly efficient approach in additive engineering for improving the efficiency and stability of CsPbBr3 PSCs. It was found that phenethylammonium iodide can passivate interface defects, suppress non-radiative recombination, and increase the grain sizes of CsPbBr3 films by optimizing crystal quality and interface contact. As a result, a carbon-based CsPbBr3 PSC with power conversion efficiency > 8.51%, storage stability > 340 days, and excellent harsh stability under high temperature and humidity, has been achieved.

In this study, we proposed a new adjacent variable thickness hexagonal tube (AVTHT) and performed crushing analysis and crashworthiness optimization under multiple loadings. First, the finite element models were constructed and validated by experiments with four configurations of AVTHTs. Then, the numerical simulations under axial loading and multiple oblique loadings indicated that AVTHTs under various loading angles (0°, 10°, 20°, and 30°) and three patterns (α, β, and θ) exhibited different deformation modes, force-displacement characteristics, and crashworthiness indices. This suggested that we could change and determine the plate thickness configuration to make the AVTHTs exhibit the expected crushing performance under multiple loadings. Therefore, multi-objective optimization for minimizing maximum crushing force with multiple loadings (Fmaxw) and maximizing specific energy absorption with multiple loadings (SEAw) by changing the thickness configuration under multiple loadings was conducted. The results determined the thickness design domains and indicated that certain thickness ranges should be avoided, such as the ranges of 1.55≤t1≤1.6 and 1.85≤t1≤1.95, which was helpful for getting AVTHTs to achieve excellent crushing performance in railway vehicles. In the pareto results, increasing t1 would not always increase the Fmaxw and SEAw. For example, when 1.75≤t1≤1.8, increasing t1 would lead to decline of Fmaxw and SEAw.

Tumor heterogeneity presents challenges for personalized diagnosis and treatment of cancer. The identification method of cancer-specific biomarkers has important applications for the diagnosis and treatment of cancer types. In this study, we analyzed the pan-cancer DNA methylation data from TCGA and GEO, and proposed a computational method to quantify the degree of specificity based on the level of DNA methylation of G protein-coupled receptor-related genes (GPCRs-related genes) and to identify specific GPCRs DNA methylation biomarkers (GRSDMs) in pan-cancer. Then, a ridge regression-based method was used to discover potential drugs through predicting the drug sensitivities of cancer samples. Finally, we predicted and verified 8 GRSDMs in adrenocortical carcinoma (ACC), rectum adenocarcinoma (READ), uveal Melanoma (UVM), thyroid carcinoma (THCA), and predicted 4 GRSDMs (F2RL3, DGKB, GRK5, PIK3R6) which were sensitive to 12 potential drugs. Our research provided a novel approach for the personalized diagnosis of cancer and informed individualized treatment decisions.