Search

Abstract Background Prostate cancer is one of the most common malignant tumors in middle-aged and elderly men and carries significant prognostic implications, and recent studies suggest that dual-energy computed tomography (DECT) utilizing new virtual monoenergetic images can enhance cancer detection rates. This study aimed to assess the impact of virtual monoenergetic images reconstructed from DECT arterial phase scans on the image quality of prostate lesions and their diagnostic performance for prostate cancer. Methods We conducted a retrospective analysis of 83 patients with prostate cancer or prostatic hyperplasia who underwent DECT scans at Meizhou People’s Hospital between July 2019 and December 2023. The variables analyzed included age, tumor diameter and serum prostate-specific antigen (PSA) levels, among others. We also compared CT values, signal-to-noise ratio (SNR), subjective image quality ratings, and contrast-to-noise ratio (CNR) between virtual monoenergetic images (40–100 keV) and conventional linear blending images. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic efficacy of virtual monoenergetic images (40 keV and 50 keV) compared to conventional images. Results Virtual monoenergetic images at 40 keV showed significantly higher CT values (168.19 ± 57.14) compared to conventional linear blending images (66.66 ± 15.5) for prostate cancer (P

Abstract Neurons, exhibiting unique polarized structures, rely primarily on the mitochondrial production of ATP to maintain their hypermetabolic energy requirements. To maintain a normal energy supply, mitochondria are transported to the distal end of the axon. When mitochondria within the axon are critically damaged beyond their compensatory capacity, they are cleared via autophagosomal phagocytosis, and the degradation products are recycled to replenish energy. When the mitochondria are dysfunctional or their transport processes are blocked, axons become susceptible to degeneration triggered by energy depletion, resulting in neurodegenerative diseases. As the final checkpoint for mitochondrial quality control, axonal mitophagy is vital for neuronal growth, development, injury, and regeneration. Furthermore, abnormal axonal mitophagy is crucial in the pathogenesis of optic nerve-related diseases such as glaucoma. We review recent studies on axonal mitophagy and summarize the progress of research on axonal mitophagy in optic nerve-related diseases to provide insights into diseases associated with axonal damage in optic ganglion cells.

Abstract Spinal diseases and frozen shoulder are prevalent health problems in Asian populations. Early assessment and treatment are very important to prevent the disease from getting worse and reduce pain. In the field of computer vision, it is a challenging problem to assess the range of motion. In order to realize efficient, real-time and accurate assessment of the range of motion, an assessment system combining MediaPipe and YOLOv5 technologies was proposed in this study. On this basis, Convolutional Block Attention Module (CBAM) is introduced into the YOLOv5 target detection model, which can enhance the extraction of feature information, suppress background interference, and improve the generalization ability of the model. In order to meet the requirements of large-scale computing, a client/server (C/S) framework structure is adopted. The evaluation results can be obtained quickly after the client uploads the image data, providing a convenient and practical solution. In addition, a game of "Picking Bayberries" was developed as an auxiliary treatment method to provide patients with interesting rehabilitation training.

Abstract Background Fish reproduction, development and growth are directly affected by temperature, investigating the regulatory mechanisms behind high temperature stress is helpful to construct a finer molecular network. In this study, we systematically analyzed the transcriptome and miRNA information of American shad (Alosa sapidissima) liver tissues at different cultivation temperatures of 24 ℃ (Low), 27 ℃ (Mid) and 30 ℃ (High) based on a high-throughput sequencing platform. Results The results showed that there were 1594 differentially expressed genes (DEGs) and 660 differentially expressed miRNAs (DEMs) in the LowLi vs. MidLi comparison group, 473 DEGs and 84 DEMs in the MidLi vs. HighLi group, 914 DEGs and 442 DEMs in the LowLi vs. HighLi group. These included some important genes and miRNAs such as calr, hsp90b1, hsp70, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p. The DEGs were mainly enriched in the protein folding, processing and export pathways of the endoplasmic reticulum; the target genes of the DEMs were mainly enriched in the focal adhesion pathway. Furthermore, the association analysis revealed that the key genes were mainly enriched in the metabolic pathway. Interestingly, we found a significant increase in the number of genes and miRNAs involved in the regulation of heat stress during the temperature change from 24 °C to 27 °C. In addition, we examined the tissue expression characteristics of some key genes and miRNAs by qPCR, and found that calr, hsp90b1 and dre-miR-125b-2-3p were significantly highly expressed in the liver at 27 ℃, while novel-m0481-5p, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p had the highest expression in the heart at 30℃. Finally, the quantitative expression trends of 10 randomly selected DEGs and 10 DEMs were consistent with the sequencing data, indicating the reliability of the results. Conclusions In summary, this study provides some fundamental data for subsequent in-depth research into the molecular regulatory mechanisms of A. sapidissima response to heat stress, and for the selective breeding of high temperature tolerant varieties.

Abstract Triple negative breast cancer (TNBC) is a type of cancer that lacks receptor expression and has complex molecular mechanisms. Recent evidence shows that the ubiquitin-protease system is closely related to TNBC. In this study, we obtain a key ubiquitination regulatory substrate-ABI2 protein by bioinformatics methods, which is also closely related to the survival and prognosis of TNBC. Further, through a series of experiments, we demonstrated that ABI2 expressed at a low level in TNBC tumors, and it has the ability to control cell cycle and inhibit TNBC cell migration, invasion and proliferation. Molecular mechanism studies proved E3 ligase CBLC could increase the ubiquitination degradation of ABI2 protein. Meanwhile, RNA-seq and IP experiments indicated that ABI2, acting as a crucial factor of tumor suppression, can significantly inhibit PI3K/Akt signaling pathway via the interaction with Rho GTPase RAC1. Finally, based on TNBC drug target ABI2, we screened and found that FDA-approved drug Colistimethate sodium(CS) has significant potential in suppressing the proliferation of TNBC cells and inducing cell apoptosis, making it a promising candidate for impeding the progression of TNBC.

The discovery of deserialization vulnerabilities has garnered significant attention from cybersecurity researchers, with an increasing number of vulnerabilities being uncovered, posing severe threats to enterprise network security. The Java language's polymorphism and reflection capabilities render its deserialization vulnerability exploitation chains more varied and intricate, amplifying the challenges in defense and detection efforts. Consequently, developing strategies to counter Java deserialization vulnerability attacks has become a critical aspect of network security. Following an examination of numerous publicly known Java deserialization vulnerabilities, a runtime detection-based defense technology solution for Java deserialization vulnerabilities was proposed. Deserialization vulnerabilities were categorized into four types based on the data formats involved: Java native deserialization vulnerability, JSON deserialization vulnerability, XML deserialization vulnerability, and YAML deserialization vulnerability. For each type, the entry function within the exploitation process was identified and summarized. Utilizing Java's runtime protection technology, the solution monitored sensitive behaviors, such as command execution at the Java level, and captured the current runtime context information of the system. By correlating the deserialization entry function with the context information, the system can determine if the current behavior constitutes an exploitation of a deserialization vulnerability. The solution's efficacy was validated through testing on prevalent Java applications, including WebLogic, JBoss, and Jenkins. The results demonstrate that this approach can effectively protect against Java deserialization vulnerability attacks without inflicting a substantial performance penalty on the targeted system. Furthermore, when compared to other mainstream protection solutions, this method exhibits superior protective efficacy.

Abstract PANoptosis plays a crucial role in cancer initiation and progression. However, the roles of PANoptosis-related genes (PARGs) in the prognosis and immune landscape of head and neck squamous cell carcinoma (HNSCC) remain unclear. Integrated bioinformatics analyses based on the data of HNSCC patients in the TCGA database were conducted. We extracted 48 PARGs expression profile and then conducted differentially expressed analysis, following building a Cox model to predict the survival of HNSCC patients. Subsequently, the relationships between the risk score, immune landscape, chemo-, and immune-therapy responses were analyzed, respectively. Moreover, we investigated the prognostic value, and further predicted the pathways influenced by PARGs. Finally, we identified the biological function of crucial PARGs. A total of 18 differentially expressed PARGs were identified in HNSCC, and a Cox model including CASP8, FADD, NLRP1, TNF, and ZBP1 was constructed, which showed that the risk score was associated with the prognosis as well as immune infiltration of HNSCC patients, and the risk score could be regarded as an independent biomarker. Additionally, patients with high-risk score might be an indicator of lymph node metastasis and advanced clinical stage. High-risk scores also contributed to the chemotherapy resistance and immune escape of HNSCC patients. In addition, FADD and ZBP1 played a crucial role in various cancer-related pathways, such as the MAPK, WNT, and MTOR signaling pathways. On the other hand, we suggested that FADD facilitated the progression and 5-fluorouracil (5-FU) resistance of HNSCC cells. A signature based on PANoptosis showed great predictive power for lymph node metastasis and advanced stage, suggesting that the risk score might be an independent prognostic biomarker for HNSCC. Meanwhile, FADD, identified as a prognostic biomarker, may represent an effective therapeutic target for HNSCC.

Abstract GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65’s transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.

Abstract Tissue engineering has demonstrated its efficacy in promoting tissue regeneration, and extensive research has explored its application in rotator cuff (RC) tears. However, there remains a paucity of research translating from bench to clinic. A key challenge in RC repair is the healing of tendon–bone interface (TBI), for which bioactive materials suitable for interface repair are still lacking. The umbilical cord (UC), which serves as a vital repository of bioactive components in nature, is emerging as an important source of tissue engineering materials. A minimally manipulated approach is used to fabricate UC scaffolds that retain a wealth of bioactive components and cytokines. The scaffold demonstrates the ability to modulate the TBI healing microenvironment by facilitating cell proliferation, migration, suppressing inflammation, and inducing chondrogenic differentiation. This foundation sets the stage for in vivo validation and clinical translation. Following implantation of UC scaffolds in the canine model, comprehensive assessments, including MRI and histological analysis confirm their efficacy in inducing TBI reconstruction. Encouraging short‐term clinical results further suggest the ability of UC scaffolds to effectively enhance RC repair. This investigation explores the mechanisms underlying the promotion of TBI repair by UC scaffolds, providing key insights for clinical application and translational research.

Diabetic wounds are serious clinical complications which manifest wet condition due to the mass exudate, along with disturbed regulation of inflammation, severe oxidative stress and repetitive bacterial infection. Existing treatments for diabetic wounds remain unsatisfactory due to the lack of ideal dressings that encompass mechanical performance, adherence to moist tissue surfaces, quick repair, and diverse therapeutic benefits. Herein, we fabricated a wet adhesive, self-healing, glucose-responsive drug releasing hydrogel with efficient antimicrobial and pro-healing properties for diabetic wound treatment. PAE hydrogel was constructed with poly(acrylic acid-co-acrylamide) (AA-Am) integrated with a dynamic E-F crosslinker, which consisted of epigallocatechin gallate (EGCG) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA). Due to the dynamic crosslinking nature of boronate esters, abundant catechol groups and hydrogen bonding, PAE hydrogel demonstrated excellent mechanical properties with about 1000 % elongation, robust adhesion to moist tissues, fast self-healing, and absorption of biofluids of 10 times of its own weight. Importantly, PAE hydrogel exhibited sustained and glucose-responsive release of EGCG. Together, the bioactive PAE hydrogel had effective antibacterial, antioxidative, and anti-inflammatory properties in vitro, and accelerated diabetic wound healing in rats via reducing tissue-inflammatory response, enhancing angiogenesis, and reprogramming of macrophages. Overall, this versatile hydrogel provides a straightforward solution for the treatment of diabetic wound, and shows potential for other wound-related application scenarios.

Abstract Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ+) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Abstract The Ningdong coalfield has played a pivotal role in advancing local economic development and meeting national energy. Nevertheless, mining operations have engendered ecological challenges encompassing subterranean water depletion, land desertification, and ground subsidence, primarily stemming from the disruption of coal seam roof strata. Consequently, the local ecosystem has incurred substantial harm. Water-preserved coal mining presently constitutes the pivotal technology in mitigating this problem. The primary challenge of this technique lies in identifying critical aquifer layers and understanding the heights of water-conducting fracture zones. To obtain a precise comprehension of the seepage patterns within the upper coal seam aquifer during mining, delineate the extent of water-conducting fracture zones, non-invasive geophysical techniques such as time-lapse electrical resistivity tomography (TL-ERT), magnetic resonance sounding (MRS), and spontaneous potential (SP) have been employed to monitor alterations within the shallow coalfield’s aquifer throughout the mining process in the Ningdong coalfield. By conducting meticulous examinations of fluctuations in resistivity, moisture content, and self-potential within the superjacent strata during coal seam extraction, the predominant underground water infiltration strata were ascertained, concurrently enabling the estimation of the development elevation of water-conducting fracture zones. This outcome furnishes a geophysical underpinning for endeavors concerning local water-preserved coal mining and ecological rehabilitation.

Abstract Heart failure is the prevalent complication of acute myocardial infarction. We aim to identify a biomarker for heart failure post-acute myocardial infarction. This observational study includes 1062 and 1043 patients with acute myocardial infarction in the discovery and validation cohorts, respectively. The outcomes are in-hospital and long-term heart failure events. S100A8/A9 is screened out through proteomic analysis, and elevated circulating S100A8/A9 is independently associated with heart failure in discovery and validation cohorts. Furthermore, the predictive value of S100A8/A9 is superior to the traditional biomarkers, and the addition of S100A8/A9 improves the risk estimation using traditional risk factors. We finally report causal effect of S100A8/A9 on heart failure in three independent cohorts using Mendelian randomization approach. Here, we show that S100A8/A9 is a predictor and potentially causal medicator for heart failure post-acute myocardial infarction.

Abstract Background Guillain–Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral nervous system. Methods Initially, we assessed the expression of purinergic P2X7R in the peripheral blood of patients with GBS using flow cytometry and qRT-PCR. Next, we explored the expression of P2 X7R in CD4+ T cells, CD8+ T cells, and macrophages within the sciatic nerves and spleens of rats using immunofluorescence labeling and flow cytometry. The P2X7R antagonist brilliant blue G (BBG) was employed to examine its therapeutic impact on rats with experimental autoimmune neuritis (EAN) induced by immunization with the P0180 − 199 peptide. We analyzed CD4+ T cell differentiation in splenic mononuclear cells using flow cytometry, assessed Th17 cell differentiation in the sciatic nerve through immunofluorescence staining, and examined the expression of pro-inflammatory cytokine mRNA using RT-PCR. Additionally, we performed protein blotting to assess the expression of P2X7R and NLRP3-related inflammatory proteins within the sciatic nerve. Lastly, we utilized flow cytometry and immunofluorescence labeling to examine the expression of NLRP3 on CD4+ T cells in rats with EAN. Results P2X7R expression was elevated not only in the peripheral blood of patients with GBS but also in rats with EAN. In rats with EAN, inhibiting P2X7R with BBG alleviated neurological symptoms, reduced demyelination, decreased inflammatory cell infiltration of the peripheral nerves, and improved nerve conduction. BBG also limited the production of pro-inflammatory molecules, down-regulated the expression of P2X7R and NLRP3, and suppressed the differentiation of Th1 and Th17 cells, thus protecting against EAN. These effects collectively contribute to modifying the inflammatory environment and enhancing outcomes in EAN rats. Conclusions Suppression of P2X7R relieved EAN manifestation by regulating CD4+ T cell differentiation and NLRP3 inflammasome activation. This finding underscores the potential significance of P2X7R as a target for anti-inflammatory treatments, advancing research and management of GBS.

Abstract Parkinson’s disease is the world’s fastest-growing neurological disorder. Research to elucidate the mechanisms of Parkinson’s disease and automate diagnostics would greatly improve the treatment of patients with Parkinson’s disease. Current diagnostic methods are expensive and have limited availability. Considering the insidious and preclinical onset and progression of the disease, a desirable screening should be diagnostically accurate even before the onset of symptoms to allow medical interventions. We highlight retinal fundus imaging, often termed a window to the brain, as a diagnostic screening modality for Parkinson’s disease. We conducted a systematic evaluation of conventional machine learning and deep learning techniques to classify Parkinson’s disease from UK Biobank fundus imaging. Our results suggest Parkinson’s disease individuals can be differentiated from age and gender-matched healthy subjects with 68% accuracy. This accuracy is maintained when predicting either prevalent or incident Parkinson’s disease. Explainability and trustworthiness are enhanced by visual attribution maps of localized biomarkers and quantified metrics of model robustness to data perturbations.

Abstract The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). MYC is considered undruggable to date. Here, we comprehensively identify genes essential for survival of MYC high but not MYC low cells by a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen uncovers novel MYC synthetic lethal (MYC-SL) interactions and identifies most MYC-SL genes described previously. In particular, the screen reveals nucleocytoplasmic transport to be a MYC-SL interaction. We show that the majority of MYC-SL nucleocytoplasmic transport genes are upregulated in MYC high murine HCC and are associated with poor survival in HCC patients. Inhibiting Exportin-1 (XPO1) in vivo induces marked tumor regression in an autochthonous MYC-transgenic HCC model and inhibits tumor growth in HCC patient-derived xenografts. XPO1 expression is associated with poor prognosis only in HCC patients with high MYC activity. We infer that MYC may generally regulate and require altered expression of nucleocytoplasmic transport genes for tumorigenesis.

In many military and civilian areas, there exists a scenario in which multiple intruders from an adversary attempt to enter important region of our own to carry out intentional malign activity. Adversarial Risk (AR) estimation is used to assess and predict the expected damage to our valuable assets from the actions of online adversaries based on measurements performed by sensors. To evaluate random and time-varying AR, this study proposes a stochastic AR estimation approach based on a Labeled Multi-Bernoulli (LMB) tracker. First, in the formulation of LMB filtering, expressions of the minimum mean squared error estimation of the stochastic AR are derived for the additive and multiplying model. Second, by combining the Gaussian mixture and sampling approximations, we devise a numerical calculation approach for the proposed AR estimations. Third, we achieve an online evaluation of the expected damage to our valuable assets from the adversary by embedding the proposed AR estimation and LMB filtering. The effectiveness and performance advantage of the proposed estimation algorithms are verified using measurements from radars, considering a simulated scenario wherein multiple lethal targets hit the radar positions.

Abstract When multiple influential covariates need to be balanced during a clinical trial, stratified blocked randomization and covariate-adaptive randomization procedures are frequently used in trials to prevent bias and enhance the validity of data analysis results. The latter approach is increasingly used in practice for a study with multiple covariates and limited sample sizes. Among a group of these approaches, the covariate-adaptive procedures proposed by Pocock and Simon are straightforward to be utilized in practice. We aim to investigate the optimal design parameters for the patient treatment assignment probability of their developed three methods. In addition, we seek to answer the question related to the randomization performance when additional covariates are added to the existing randomization procedure. We conducted extensive simulation studies to address these practically important questions.

Carbon fibers (CFs) reinforced alkali-activated (AA) ground granulated blast furnace slag (GGBFS) geopolymer composites have excellent mechanical and thermoelectrical properties, as well as low energy consumption and low CO2 emissions during their production. However, the dispersion of CFs in the geopolymer matrix is always a technical issue in the preparation of the green composite material. Therefore, this study comparatively investigated various dispersion methods, including, mixing sequence (pre-mixing and after-mixing methods), dispersing agent (nano silicon dioxide [nSiO2]), and ultrasonic treatment time (0, 15, 30, and 45 min), as well as CFs content (0.5, 1.0, and 1.5 wt% of GGBFS). The distribution of CFs was then qualitatively and quantitatively evaluated by a series of tests, such as flowability, electrical resistivity, flexural strength, scanning electron microscope (SEM) analysis, and X-ray computed tomography (CT). The experimental results showed that the proposed pre-mixing method provided excellent dispersion characteristics for CFs compared with the after-mixing method. The introduction of nSiO2 can enhance the dispersion of CFs and the mechanical and electrical properties of AA GGBFS geopolymer composites. At a carbon fiber content of 1.5 %, the pre-mixing method and the addition of nSiO2 dispersant reduced the resistivity of the 28-day geopolymer composites by 17.0 % and 38 %, respectively, compared with the after-mixing method. It is feasible to use X-ray CT scanning with the gray-scale frequency map to analyze the dispersion effect of CFs in AA GGBFS geopolymer composites. However, the results were not intuitive when less agglomeration of CFs occurred for the low content of CFs. The scanning method is more applicable to the sample with over 1.0 wt% CFs. The average pixel areas of uniformly dispersed CF bundles in the 2D images of the pre-mixing method and the addition of nSiO2 dispersant specimens were 3.32 % and 6.55 % higher than those of the after-mixing method, respectively. The 2D and 3D scanning results from the dispersion characteristics of CFs were consistent. 2D scanning could provide a time-consuming option for the measurement of CFs dispersion characteristics.

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to the imbalance between osteogenesis and osteoclastogenesis, making osteoporotic bone defects healing a significant clinical challenge. Calcium phosphate cement (CPC) is a promising bone substitute material due to its good osteoinductive activity, however, the drawbacks such as fragility, slow degradation rate and incapability to control bone loss restrict its application in osteoporotic bone defects treatment. Currently, we developed the PLGA electrospun nanofiber sheets to carry alendronate (ALN) and magnesium oxide nanoparticle (nMgO) into CPC, therefore, to obtain a high-strength bone cement (C/AM-PL/C). The C/AM-PL/C bone cement had high mechanical strength, anti-washout ability, good injection performance and drug sustained release capacity. More importantly, the C/AM-PL/C cement promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and neovascularization via the release of Mg2+ (from nMgO) and Ca2+ (during the degradation of CPC), and inhibited osteoclastogenesis via the release of ALN in vitro. Moreover, the injection of C/AM-PL/C cement significantly improved bone healing in an OP model with femur condyle defects in vivo. Altogether, the injectable C/AM-PL/C cement could facilitate osteoporotic bone regeneration, demonstrating its capacity as a promising candidate for treatment of osteoporotic bone defects.

Lung cancer is the leading cause of global cancer-related deaths. Platinum-based chemotherapy is the first-line treatment for the most common type of lung cancer, i.e., non-small-cell lung cancer (NSCLC), but its therapeutic efficiency is limited by chemotherapeutic resistance. Therefore, it is vital to develop effective therapeutic modalities that bypass the common molecular mechanisms associated with chemotherapeutic resistance. Ferroptosis is a form of non-apoptotic regulated cell death characterized by iron-dependent lipid peroxidation (LPO). Ferroptosis is crucial for the proper therapeutic efficacy of lung cancer-associated chemotherapies. If targeted as a novel therapeutic mechanism, ferroptosis modulators present new opportunities for increasing the therapeutic efficacy of lung cancer chemotherapy. Emerging studies have revealed that the pharmacological induction of ferroptosis using natural compounds boosts the efficacy of chemotherapy in lung cancer or drug-resistant cancer. In this review, we first discuss chemotherapeutic resistance (or chemoresistance) in lung cancer and introduce the core mechanisms behind ferroptosis. Then, we comprehensively summarize the small-molecule compounds sourced from traditional medicines that may boost the anti-tumor activity of current chemotherapeutic agents and overcome chemotherapeutic resistance in NSCLC. Cumulatively, we suggest that traditional medicines with ferroptosis-related anticancer activity could serve as a starting point to overcome chemotherapeutic resistance in NSCLC by inducing ferroptosis, highlighting new potential therapeutic regimens used to overcome chemoresistance in NSCLC.

Cobalt-free refractory high-entropy alloys (RHEAs) are strong contenders for structural materials in nuclear reactors because they do not exhibit cobalt activity under irradiation. The mechanical properties and thermal stability of RHEAs are primarily attributed to the solid solution phase, which is essentially the body-centered cubic (BCC) phase. The BCC phase formation rules thus became the basic criterion in the compositional design of RHEAs. In this paper, the BCC phase formation rules in cobalt-free RHEAs were determined via the calculation of six semiempirical parameters, namely, the entropy of mixing, enthalpy of mixing, atomic size difference, Ω-parameter, d-orbital energy level and valance electron concentration. The mixing enthalpy and atomic size differences are more effective than other semiempirical parameters for predicting BCC phase stability in cobalt-free RHEAs. The presence of aluminum is found to cause a notable alteration in the range of phase stability in cobalt-free RHEAs.

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other cell death modes, plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications and posttranslational modifications (PTMs) promote anticancer drug resistance, cancer progression, and metastasis. Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases (NSDs), cardiovascular diseases (CVDs), liver diseases, lung diseases, and kidney diseases. In this review, we first summarize the core molecular mechanisms of ferroptosis. Then, the roles of epigenetic processes, including histone PTMs, DNA methylation, and noncoding RNA regulation and PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, methylation, and ADP-ribosylation, are concisely discussed. The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases, including cancers, NSD, CVDs, liver diseases, lung diseases, and kidney diseases, as well as the application of epigenetic and PTM modulators in the therapy of these diseases, are then discussed in detail. Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other diseases. In addition, these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

In light of a global rise in the number of patients with type 2 diabetes mellitus (T2DM) and obesity, non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of hepatocellular carcinoma (HCC), with the annual occurrence of MASLD-driven HCC expected to increase by 45%–130% by 2030. Although MASLD has become a serious major public health threat globally, the exact molecular mechanisms mediating MASLD-driven HCC remain an open problem, necessitating future investigation. Meanwhile, emerging studies are focusing on the utility of bioactive compounds to halt the progression of MASLD to MASLD-driven HCC. In this review, we first briefly review the recent progress of the possible mechanisms of pathogenesis and progression for MASLD-driven HCC. We then discuss the application of bioactive compounds to mitigate MASLD-driven HCC through different modulatory mechanisms encompassing anti-inflammatory, lipid metabolic, and gut microbial pathways, providing valuable information for future treatment and prevention of MASLD-driven HCC. Nonetheless, clinical research exploring the effectiveness of herbal medicines in the treatment of MASLD-driven HCC is still warranted.

Considering the high-speed and high power density technical specifications of new energy vehicle motors, there is a growing demand for rotor strength as motor peak speeds reach 20,000 r/min and beyond. The utilization of non-oriented silicon steel with a high yield strength in rotors has emerged as a promising approach to increase motor speed. However, the magnetic and mechanical properties of high-strength silicon steel under variable temperature conditions have not been fully explored, particularly in regards to their impact on motor torque, efficiency, and speed. This manuscript investigates the behavior of high-strength silicon steel before and after annealing and at different temperatures, analyzing its influence on high-speed motor performance. The validity and feasibility of this study are confirmed through prototype testing, providing a comprehensive reference for engineering design.

The Neoproterozoic Bure adakitic rock in the western Ethiopia shield is a newly discovered magmatic rock type. However, the physicochemical conditions during its formation, and its source characteristics are still not clear, restricting a full understanding of its petrogenesis and geodynamic evolution. In this study, in order to shed light on the physicochemical conditions during rock formation and provide further constraints on the petrogenesis of the Bure adakitic rock, we conduct electron microprobe analysis on K-feldspar, plagioclase, and biotite. Additionally, we investigate the trace elements and Hf isotopes of zircon, and the Sr-Nd isotopes of the whole rock. The results show that the K-feldspar is orthoclase (Or = 89.08~96.37), the plagioclase is oligoclase (Ab = 74.63~85.99), and the biotite is magnesio-biotite. Based on the biotite analysis results, we calculate that the pressure during rock formation was 1.75~2.81 kbar (average value of 2.09 kbar), representing a depth of approximately 6.39~10.2 km (average value of 7.60 km). The zircon thermometer yields a crystallization temperature of 659~814 °C. Most of the (Ce/Ce*)D values in the zircons plotted above the Ni-NiO oxygen buffer pair, and the calculated magmatic oxygen fugacity (logfO2) values vary from −18.5 to −4.9, revealing a relatively high magma oxygen fugacity. The uniform contents of FeO, MgO, and K2O in the biotite suggest a crustal magma source for the Bure adakitic rock. The relatively low (87Sr/86Sr)i values of 0.70088 to 0.70275, positive εNd(t) values of 3.26 to 7.28, together with the positive εHf(t) values of 7.64~12.99, suggest that the magma was sourced from a Neoproterozoic juvenile crust, with no discernable involvement of a pre-Neoproterozoic continental crust, which is coeval with early magmatic stages in the Arabian Nubian Shield elsewhere. Additionally, the mean Nd model ages demonstrate an increasing trend from the northern parts (Egypt, Sudan, Afif terrane of Arabia, and Eritrea and northern Ethiopia; 0.87 Ga) to the central parts (Western Ethiopia shield; 1.03 Ga) and southern parts (Southern Ethiopia Shield, 1.13 Ga; Kenya, 1.2 Ga) of the East African Orogen, which indicate an increasing contribution of pre-Pan-African crust towards the southern part of the East African Orogen. Based on the negative correlation between MgO and Al2O3 in the biotite, together with the Lu/Hf-Y and Yb-Y results of the zircon, we infer that the Bure adakitic rock was formed in an arc–arc collision orogenic environment. Combining this inference with the whole rock geochemistry and U-Pb age of the Bure adakitic rock, we further propose that the rock is the product of thickened juvenile crust melting triggered by the Neoproterozoic Pan-African Orogeny.

Abstract Background As a common malignant tumour, pancreatic cancer (PC) has the worst clinical outcome. Early evaluation of the postoperative prognosis has certain clinical value. Low-density lipoprotein cholesterol (LDL-c), which is mainly composed of cholesteryl esters, phospholipids, and proteins, plays an important role in transporting cholesterol into peripheral tissues. LDL-c has also been reported to be correlated with the occurrence and progression of malignant tumours and can predict postoperative prognosis in various tumours. Aims To determine correlation between serum LDL-c level and clinical outcome in PC patients after surgery. Methods Data of PC patients that received surgery at our department from January 2015 to December 2021 were retrospectively analysed. Receiver operating characteristic (ROC) curves between perioperative serum LDL-c at different timepoints and survival rate at postoperative 1-year were drawn, and the optimal cut-off value was calculated. Patients were categorized into low and high LDL-c groups, and their clinical data and outcome were compared. Univariate and multivariate analyses were applied to screen out risk markers for poor prognosis of PC patients after surgery. Results The area under the ROC curve of serum LDL-c at 4 weeks after surgery and prognosis was 0.669 (95% CI: 0.581–0.757), and the optimal cut-off value was 1.515 mmol/L. The median disease-free survival (DFS) rates of low and high LDL-c groups were 9 months and 16 months, respectively, and the 1-, 2- and 3-year DFS rates were 42.6%, 21.1% and 11.7% in low LDL-c group, respectively, and, 60.2%, 35.3% and 26.2% in high LDL-c group, respectively (P = 0.005). The median overall survival (OS) rates of low and high LDL-c groups were 12 months and 22 months, respectively, and the 1-, 2- and 3-year OS rates were 46.8%, 22.6% and 15.8% in low LDL-c group, respectively, and 77.9%, 46.8% and 30.4% in high LDL-c group, respectively (P = 0.004). Multivariate analysis confirmed low postoperative 4-week serum LDL-c as independent risk marker for early tumour recrudesce and poor clinical outcome in PC patients. Conclusion High postoperative 4-week serum LDL-c is a prognostic marker for prolonged DFS and OS time in PC patients.

A new dianhydride 9,10-diphenyl-9,10-bis(trifluoromethyl)-9,10-dihydroanthracene-2,3,6,7-tetraacid dianhydride (6FDPDA) with rigid semi-alicyclic structure was reported. CPI materials were prepared by copolymerizing 6FDPDA with 3,3′,4,4′-biphenyl tetracarboxylic dianhydride (BPDA) or 4,4’-(hexafluoroisopropene) diphthalic anhydride (6FDA) respectively, with 2,2′-bistrifluoromethyl benzidine (TFDB) as the diamine building blocks. Due to the ladder semi-alicyclic structure as well as –CF3 and phenyl large side groups, this new dianhydride exhibits two important advantages, the cut-off conjugated in the polymer backbone and suppressed intermolecular stacking. When 6FDA as the dianhydride comonomer, the obtained CPIs exhibits distinguished performance with transmission of 90 % at 550 nm, YI of 2.45, CTE of 16.5 ppm/K and Tg over 450 °C. These results demonstrated that 6FDPDA is an excellent building block to prepare the high performance CPIs in optoelectronic devices, for an example the substrates for flexible AMOLED display.

Climate change and human development will lead to an increase in groundwater levels. This will have a particularly severe impact on arid ecosystems that are highly dependent on groundwater, as overconsumption and pollution of water resources can lead to faster depletion of groundwater. This not only exacerbates the problem of groundwater scarcity, but also may have profound impacts on local ecological environment and biodiversity. However, previous research has focused on aboveground trait responses to precipitation deficits, with less emphasis on concomitant belowground impacts and deep soil drought from groundwater depletion. Therefore, it remains unclear how groundwater depletion affects above and belowground traits of plant to jointly regulate aboveground biomass. In this study, we assessed morphological and ecophysiological traits of two dominant species (herb: Pennisetum centrasiaticum and shrub: Artemisia halodendron) across three groundwater depth (50 cm, 100 cm, and 200 cm) in the Horqin Sandy Land in China, within which photosynthetic rate (Photo), stomatal conductance (Cond), transpiration rate (Tr), internal CO2 concentration (Ci), instantaneous water-use efficiency of leaves (Lwue), total nitrogen (LN) and phosphorus (LP) content of the leaves, root to shoot ratio (RSR), root length density (RLD), total root length (RTL), root length ratio (RLR) were measured. The result showed that the two species growing with increased groundwater depth had reduced photosynthetic rate, and regulated stomatal close to aggregate ability of instantaneous water use efficiency, which may allow plants to meet resource demands under drought stress avoiding transpiration water loss. Plants also reduced the density of all roots and adjusted the vertical distribution of coarse root by changing biomass distribution to acquire deeper soil available water. Correlation analysis showed that the vital traits for aboveground biomass responses appear to be groundwater depth, soil moisture, leaf area, photosynthesis, water use efficiency, and root traits. Overall, the biomass production response of two dominant species may be greatly influenced by the interaction between aboveground and belowground traits in response to changes in groundwater depth. This result contributes to our understanding of adaptive strategies of vegetation in sandy soils and provides additional support for enhancing vegetation productivity in semi-arid ecosystems. The ability of semi-arid ecosystems to predict vegetation dynamics under current and future increasing groundwater depths is crucial.

The aim of this study was to elucidate the application of ultrasound examination of umbilical artery (UA) hemodynamics with urine microalbumin (UmA) determination in evaluating the outcomes of sPE patients. Altogether 80 sPE patients and 75 healthy pregnant women were recruited. UmA, RI (resistance index) and PI (pulsatility index) were separately measured by ELISA and the ultrasonic Doppler flow detector. The correlation between parameters was analysed using Pearson’s coefficient method. The independent risk factors of sPE were identified using the Logistic regression model. sPE patients had increased UmA, RI and PI (all p

Investigation of cell-to-cell variability holds critical physiological and clinical implications. Thus, numerous new techniques have been developed for studying cell-to-cell variability, and these single-cell techniques can also be used to investigate rare cells. Moreover, for studying protein-protein interactions (PPIs) in single cells, several techniques have been developed based on the principle of the single-molecule pulldown (SiMPull) assay. However, the applicability of these single-cell SiMPull (sc-SiMPull) techniques is limited because of their high technical barrier and special requirements for target cells and molecules. Here, we report a highly innovative nanobead-based approach for sc-SiMPull that is based on our recently developed microbead-based, improved version of SiMPull for cell populations. In our sc-SiMPull method, single cells are captured in microwells and lysed in situ, after which commercially available, pre-surface-functionalized magnetic nanobeads are placed in the microwells to specifically capture proteins of interest together with their binding partners from cell extracts; subsequently, the PPIs are examined under a microscope at the single-molecule level. Relative to previously published methods, nanobead-based sc-SiMPull is considerably faster, easier to use, more reproducible, and more versatile for distinct cell types and protein molecules, and yet provides similar sensitivity and signal-to-background ratio. These crucial features should enable universal application of our method to the study of PPIs in single cells.

Soil extracellular enzyme activity (EEA) and enzyme stoichiometry are indicators of soil nutrient availability and microbial substrate limitation. However, the patterns in soil enzyme activities and stoichiometry, and their key drivers remain unclear during vegetation restoration in degraded sandy land. Here, soil ecosystems at five restoration stages of degraded sandy land were selected for investigation and we quantified the microbial nutrient limitation using EEA stoichiometry. The average C:N:P ratio for the nutrient-acquisition enzymes was 1:0.88:0.86, which differed from the global ratio of 1:1:1, indicating stronger microbial C limitation than N or P limitation. With vegetation restoration, the enzyme N:P ratio decreased, but the angle term used in vector analysis increased, indicating that the restored grassland transitioned from N-restricted (angle < 45°) to P-restricted (angle > 45°). Plant C inputs increased the soil nutrient content and significantly decreased the microbial C and N limitation but increased P limitation due to nutrient competition between plants and soil microorganisms. Decreased soil water levels caused by vegetation transpiration may have shifted the microbial limitation from N to P. The decreased fungi:bacteria ratio strengthened the microbial C and N or P limitations. On the basis of these findings, as measures to alleviate the associated nutrient limitations, we would recommend supplementation with phosphorus in the potential and slight stages of rocky desertification and the supplementary application of nitrogen in the moderate and severe stages during the restoration of degraded sandy ecosystems.

Injectable materials show their special merits in regeneration of damaged/degenerated bones in minimally-invasive approach. Injectable calcium phosphate bone cement (CPC) has attracted broad attention for its bioactivity, as compared to non-degradable polymethyl methacrylate cement. However, its brittleness, poor anti-washout property and uncontrollable biodegradability are the main challenges to limit its further clinical application mainly because of its stone-like dense structure and fragile inorganic-salt weakness. Herein, we developed a kind of injectable CPC bone cement with porous structure and improved robustness by incorporating poly(lactide-co-glycolic acid) (PLGA) nanofiber into CPC, with carboxymethyl cellulose (CMC) to offer good injectability as well as anti-wash-out capacity. Furthermore, the introduction of PLGA and CMC also enabled a formation of initial porous structure in the cements, where PLGA nanofiber endowed the cement with a dynamically controllable biodegradability which provided room for cell movement and bone ingrowth. Interestingly, the reinforced biodegradable cement afforded a sustainable provision of Ca2+ bioactive components, together with its porous structure, to improve synergistically new bone formation and osteo-integration in vivo by using a rat model of femur condyle defect. Further study on regenerative mechanisms indicated that the good minimally-invasive bone regeneration may come from the synergistic enhanced osteogenic effect of calcium ion enrichment and the improved revascularization capacity contributed from the porosity as well as the lactic acid released from PLGA nanofiber. These results indicate the injectable bone cement with high strength, anti-washout property and controllable biodegradability is a promising candidate for bone regeneration in a minimally-invasive approach.

The aim of this study was to observe the outcomes of newborn screening (NBS) in a certain population by using next-generation sequencing (NGS) as a first-tier screening test combined with tandem mass spectrometry (MS/MS). We performed a multicenter study of 29,601 newborns from eight screening centers with NBS via NGS combined with MS/MS. A custom-designed panel targeting the coding region of the 142 genes of 128 inborn errors of metabolism (IEMs) was applied as a first-tier screening test, and expanded NBS using MS/MS was executed simultaneously. In total, 52 genes associated with the 38 IEMs screened by MS/MS were analyzed. The NBS performance of these two methods was analyzed and compared respectively. A total of 23 IEMs were diagnosed via NGS combined with MS/MS. The incidence of IEMs was approximately 1 in 1287. Within separate statistical analyses, the positive predictive value (PPV) for MS/MS was 5.29%, and the sensitivity was 91.3%. However, for genetic screening alone, the PPV for NGS was 70.83%, with 73.91% sensitivity. The three most common IEMs were methylmalonic academia (MMA), primary carnitine deficiency (PCD) and phenylketonuria (PKU). The five genes with the most common carrier frequencies were PAH (1:42), PRODH (1:51), MMACHC (1:52), SLC25A13 (1:55) and SLC22A5 (1:63). Our study showed that NBS combined with NGS and MS/MS improves the performance of screening methods, optimizes the process, and provides accurate diagnoses.

This study investigates the synthesis of mesophase pitch using low-cost fluid catalytic cracking (FCC) slurry and waste fluid asphaltene (WFA) as raw materials through the co-carbonization method. The resulting mesophase pitch product and its formation mechanism were thoroughly analyzed. Various characterization techniques, including polarizing microscopy, softening point measurement, Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA), were employed to characterize and analyze the properties and structure of the mesophase pitch. The experimental results demonstrate that the optimal optical texture of the mesophase product is achieved under specific reaction conditions, including a temperature of 420 °C, pressure of 1 MPa, reaction time of 6 h, and the addition of 2% asphaltene. It was observed that a small amount of asphaltene contributes to the formation of mesophase pitch spheres, facilitating the development of the mesophase. However, excessive content of asphaltene may cover the surface of the mesophase spheres, impeding the contact between them and consequently compromising the optical texture of the mesophase pitch product. Furthermore, the inclusion of asphaltene promotes polymerization reactions in the system, leading to an increase in the average molecular weight of the mesophase pitch. Notably, when the amount of asphaltene added is 2%, the mesophase pitch demonstrates the lowest ID/IG value, indicating superior molecular orientation and larger graphite-like microcrystals. Additionally, researchers found that at this asphaltene concentration, the mesophase pitch exhibits the highest degree of order, as evidenced by the maximum diffraction angle (2θ) and stacking height (Lc) values, and the minimum d002 value. Moreover, the addition of asphaltene enhances the yield and aromaticity of the mesophase pitch and significantly improves the thermal stability of the resulting product.

In the face of the rapid development of the motor industry, some motors with traditional soft magnetic materials can no longer meet the needs of the market. Using new high-saturation magnetic density materials has become a new breakthrough to improve the torque density of motors. Fe-Co alloys (1J22) have high-saturation magnetic induction strength, which can effectively improve the motor’s magnetic field strength and increase its torque density. At the same time, the temperature rise of the motor is also an important factor to consider in the motor design process. In particular, the change in core temperature caused by loss makes the coupling of the internal temperature field and the electromagnetic field of the motor more common. Therefore, it is necessary to test the temperature and magnetic properties of 1J22 together. In this paper, a coupling measurement device for magnetic properties of soft magnetic materials is built, and a 1J22 temperature field–electromagnetic field coupling experiment is completed. It is found that the maximum loss of 1J22 decreases by 4.44% with the increase in temperature; the maximum loss is 6.41% less than that of traditional silicon steel. Finally, a finite element simulation model is built to simulate the actual working conditions of the motor, and it is verified that the magnetic properties of the material at high temperature will have a certain impact on the performance of the motor.

Zygote arrest-1 (Zar1) and Wilms’ tumor 1 (Wt1) play an important role in oogenesis, with the latter also involved in testicular development and gender differentiation. Here, Lczar1 and Lcwt1b were identified in Asian seabass (Lates calcarifer), a hermaphrodite fish, as the valuable model for studying sex differentiation. The cloned cDNA fragments of Lczar1 were 1192 bp, encoding 336 amino acids, and contained a zinc-binding domain, while those of Lcwt1b cDNA were 1521 bp, encoding a peptide of 423 amino acids with a Zn finger domain belonging to Wt1b family. RT-qPCR analysis showed that Lczar1 mRNA was exclusively expressed in the ovary, while Lcwt1b mRNA was majorly expressed in the gonads in a higher amount in the testis than in the ovary. In situ hybridization results showed that Lczar1 mRNA was mainly concentrated in oogonia and oocytes at early stages in the ovary, but were undetectable in the testis. Lcwt1b mRNA was localized not only in gonadal somatic cells (the testis and ovary), but also in female and male germ cells in the early developmental stages, such as those of previtellogenic oocytes, spermatogonia, spermatocytes and spermatids. These results indicated that Lczar1 and Lcwt1b possibly play roles in gonadal development. Therefore, the findings of this study will provide a basis for clarifying the mechanism of Lczar1 and Lcwt1b in regulating germ cell development and the sex reversal of Asian seabass and even other hermaphroditic species.

Understanding the effects of groundwater depth on soil microbiota and multiple soil functions is essential for ecological restoration and the implementation of groundwater conservation. The current impact of increased groundwater levels induced by drought on soil microbiota and multifunctionality remains ambiguous, which impedes our understanding of the sustainability of water-scarce ecosystems that heavily rely on groundwater resources. This study investigated the impacts of altered groundwater depths on soil microbiota and multifunctionality in a semi-arid region. Three groundwater depth levels were studied, with different soil quality and soil moisture at each level. The deep groundwater treatment had negative impacts on diversity, network complexity of microbiota, and the relationships among microbial phylum unites. Increasing groundwater depth also changed composition of soil microbiota, reducing the relative abundance of dominant phyla including Proteobacteria and Ascomycota. Increasing groundwater depth led to changes in microbial community characteristics, which are strongly related to alterations in soil multifunctionality. Overall, our results suggest that groundwater depth had a strongly effect on soil microbiota and functionality.

Abstract Objective We investigated the predictive value of clinical factors combined with coronary artery calcium (CAC) score based on a machine learning method for obstructive coronary heart disease (CAD) on coronary computed tomography angiography (CCTA) in individuals with atypical chest pain. Methods The study included data from 1,906 individuals undergoing CCTA and CAC scanning because of atypical chest pain and without evidence for the previous CAD. A total of 63 variables including traditional cardiovascular risk factors, CAC score, laboratory results, and imaging parameters were used to build the Random forests (RF) model. Among all the participants, 70% were randomly selected to train the models on which fivefold cross-validation was done and the remaining 30% were regarded as a validation set. The prediction performance of the RF model was compared with two traditional logistic regression (LR) models. Results The incidence of obstructive CAD was 16.4%. The area under the receiver operator characteristic (ROC) for obstructive CAD of the RF model was 0.841 (95% CI 0.820–0.860), the CACS model was 0.746 (95% CI 0.722–0.769), and the clinical model was 0.810 (95% CI 0.788–0.831). The RF model was significantly superior to the other two models (p

Abstract Background Brain lactate concentrations are enhanced in response to cerebral ischemia and promote the formation of reactive astrocytes, which are major components of the neuroinflammatory response and functional recovery, following cerebral ischemia. NDRG2 is upregulated during reactive astrocyte formation. However, its regulation and function are unclear. We studied the relationship between lactate and NDRG2 in astrocytes under conditions of ischemia or oxygen–glucose deprivation (OGD). Methods We examined astrocytic NDRG2 expression after middle cerebral artery occlusion (MCAO) using western blot and immunofluorescence staining. Under hypoxia conditions, we added exogenous L-lactate sodium (lactate) to cultured primary astrocytes to explore the effects of lactate on the ubiquitination modification of NDRG2. We profiled the transcriptomic features of NDRG2 silencing in astrocytes after 8 h of OGD conditions as well as exogenous lactate treatment by performing RNA-seq. Finally, we evaluated the molecular mechanisms of NDRG2 in regulating TNFα under OGD conditions using western blot and immunohistochemistry. Results Reactive astrocytes strongly expressed NDRG2 in a rat model of MCAO. We also showed that lactate stabilizes astrocytic NDRG2 by inhibiting its ubiquitination. NDRG2 inhibition in astrocytes increased inflammation and upregulated immune-associated genes and signaling pathways. NDRG2 knockdown induced TNFα expression and secretion via c-Jun phosphorylation. Conclusions We revealed that under OGD conditions, lactate plays an important anti-inflammatory role and inhibits TNFα expression by stabilizing NDRG2, which is beneficial for neurological functional recovery. NDRG2 may be a new therapeutic target for cerebral ischemia.

Résumé Contexte La fertilité masculine est progressivement devenue un problème mondial avec des possibilités de traitement limitées. L’acide alpha-lipoïque a été utilisé dans la pratique clinique pour améliorer la qualité du sperme. Cependant, il n’existe actuellement aucune revue systématique de haute qualité sur l’évaluation des effets de l’acide alpha-lipoïque sur les paramètres du sperme. Les bases de données Cochrane, MEDLINE, EMBASE, Web of Science, Clinicaltrials.org, China National Knowledge Infrastructure Database, China Biology Medicine Database, etc., ont été utilisées. Les essais contrôlés randomisés en relation ont été recueillis et sélectionnés jusqu’au 10 mars 2022. La littérature anglaise et la littérature chinoise ont été recherchées en utilisant les termes tels que « infertilité masculine », « sperme », « spermatozoïde », « acide alpha-lipoïque », « acide α-lipoïque », « acide alpha lipoïque », « acide thioctique ». Toutes les analyses statistiques ont été effectuées par RevMan 5.3. Résultats Au total, 133 participants provenant de trois études ont été inclus. Par rapport à la thérapie simulée, le traitement par l’acide alpha-lipoïque présente une amélioration significative des paramètres de sperme qui suivent : formes anormales de spermatozoïdes (différence moyenne [DM] = -1,06 ; intervalle de confiance à 95 % [IC] = -1,29--0,84, p < 0,00001), concentration de spermatozoïdes (DM = 3,98 ; IC à 95 % = 2,28-5,67, p < 0,00001), motilité totale des spermatozoïdes (grade a + b + c) (MD = 6,68 ; IC à 95% = 4,88-8,48, p < 0,00001), motilité progressive (grade a + b) (MD = 6,90 ; IC à 95% = 5,62-8,17, p

Abstract Introduction Improving the early prediction of neoadjuvant chemotherapy (NAC) efficacy in breast cancer can lead to an improved prediction of the final prognosis of patients, which would be useful for promoting individualized treatment. This study aimed to explore the value of the combination of dynamic contrast-enhanced (DCE)-MRI parameters and apparent diffusion coefficient (ADC) values in the early prediction of pathological complete response (pCR) to NAC for breast cancer. Methods A total of 119 (range, 28−69 years) patients with biopsy-proven breast cancer who received two cycles of NAC before breast surgery were retrospectively enrolled from our hospital database. Patients were divided into pCR and non pCR groups according to their pathological responses; a total of 24 patients achieved pCR, while 95 did not. The quantitative (Ktrans; Kep; Ve; IAUC) and semiquantitative parameters (W-in; W-out; TTP) of DCE-MRI that were significantly different between groups were combined with ADC values to explore their value in the early prediction of pCR to NAC for breast cancer. The independent T test was performed to compare the differences in DCE-MRI parameters and ADC values between the two groups. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC), sensitivity and specificity were calculated to evaluate the performance of the prediction. Results The Ktrans, Kep, IAUC, ADC, W-in and TTP values were significantly different between the pCR and non pCR groups after NAC. The AUC (0.845) and specificity (95.79%) of the combined Ktrans, Kep, IAUC and ADC values were both higher than those of the individual parameters. The combination of W-in, TTP and ADC values had the highest AUC value (0.886) in predicting pCR, with a sensitivity and specificity of 87.5% and 82.11%, respectively. Conclusions The results suggested that the combination of ADC values and quantitative and semiquantitative DCE-MRI parameters, especially the combination of W-in, TTP, and ADC values, may improve the early prediction of pCR in breast cancer.

Nanoparticles can promote the accumulation of drugs in tumors. However, they find limited clinical applications because they cannot easily penetrate the stroma of cancer tissues, and it is difficult to control drug release. We developed a multiresponse multistage drug-delivery nanogel with improved tumor permeability and responsiveness to the tumor microenvironment for the controlled delivery of anticancer agents. For this purpose, ∼100 nm multistage drug delivery nanogels with pH, redox, near-infrared stimulation, and enzyme responsiveness were grown in situ using 20 nm gold nanoparticles (AuNPs) via an emulsion-aiding crosslinking technique with cysteine crosslinker. An alginate cysteine AuNP (ACA) nanocarrier can efficiently load the cationic drug doxorubicin (DOX) to produce a multistage drug delivery nanocarrier (DOX@ACA). DOX@ACA can maintain the slow release of DOX and reduce its toxicity. In cancer tissues, the high pH and reductase microenvironment combined with the in vitro delivery of alginate and near-infrared light drove drug release. The developed nanoparticles effectively inhibited cancer cells, and in vivo evaluations showed that they effectively enhanced antitumor activity while having negligible in vivo toxicity to major organs.

Chemotherapy resistance poses a major obstacle in cancer therapy. Here, the authors identify the mTOR pathway as a determinant of chemosensitivity and demonstrate that inhibition of mTOR promotes the persistence of a chemotherapy-resistant cancer-cell subpopulation.

Abstract Hydrogen energy is a promising renewable resource for the sustainable development of society. As a key member of the fuel cell (FC) family, the solid oxide fuel cell (SOFC) has attracted a lot of attention because of characteristics such as having various sources as fuel and high energy conversion efficiency, and being pollution-free. SOFC is a highly coupled, nonlinear, and multivariable complex system, and thus it is very important to design an appropriate control strategy for an SOFC system to ensure its safe, reliable, and efficient operation. This paper undertakes a comprehensive review and detailed summary of the state-of-the-art control approaches of SOFC. These approaches are divided into eight categories of control: proportional integral differential (PID), adaptive (APC), robust, model predictive (MPC), fuzzy logic (FLC), fault-tolerant (FTC), intelligent and observer-based. The SOFC control approaches are carefully evaluated in terms of objective, design, application/scenario, robustness, complexity, and accuracy. Finally, five perspectives are proposed for future research directions.

Over the last decade, the superior properties of graphene have contributed to intensive studies on the fabrication and applications of graphene nanocomposites. Ex-situ homologous recombination and recombination techniques were listed. Because of their remarkable features, including thermal conductivity and high-specific area, graphene and its derivatives have a significant prospective for medical and biological applications, including drug delivery and bio-imaging. The usage of graphene-based nanomaterials is a hot topic in medicinal research. Many research studies have been performed on graphene-based composites, but only a few reviews have been published regarding their applications in the biomedical field and potential risk factors associated with human well-being and the environment. Hence, this review paper aims to provide in-depth information on ongoing knowledge and results about the properties of graphene-based composites. The discovery, developmental methods, structural properties, and synthesis of graphene nanomaterials have been discussed. After a brief description of the most common methods used for fabricating or extracting graphene derivatives, the main steps of graphene-based composite preparation are introduced. Applications of graphene-based composites in drug delivery, medical, and biomedical fields have been addressed. Finally, the future perspectives and challenges associated with the applications of graphene-based composites have been summarized.Highlights Compositions and characteristics of nanocomposite materials reinforced with graphene, graphene oxide, reduced graphene oxide, and modified graphene.The synthesis method of graphene and the manufacturing of graphene-based composites.Latest developments in graphene-based composites for biomedical applications.Consequences of the large-scale production of graphene-based composites.

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.

IntroductionUnderstanding the impact of deep groundwater depth on vegetation communities and soil in sand dunes with different underground water tables is essential for ecological restoration and the conservation of groundwater. Furthermore, this understanding is critical for determining the threshold value of groundwater depth that ensures the survival of vegetation.MethodThis paper was conducted in a semi-arid region in eastern China, and the effects of deep groundwater depth (6.25 m, 10.61 m, and 15.26 m) on vegetation communities and soil properties (0–200 cm) across three dune types (mobile, semi-fixed, and fixed dunes) were evaluated in a sand ecosystem in the Horqin Sandy Land.ResultsFor vegetation community, variations in the same species are more significant at different groundwater depths. For soil properties, groundwater depth negatively influences soil moisture, total carbon, total nitrogen, available nitrogen, available phosphorus concentrations, and soil pH. Besides, groundwater depth also significantly affected organic carbon and available potassium concentrations. In addition, herb species were mainly distributed in areas with lower groundwater depth, yet arbor and shrub species were sparsely distributed in places with deeper groundwater depth.DiscussionAs arbor and shrub species are key drivers of ecosystem sustainability, the adaptation of these dominant species to increasing groundwater depth may alleviate the negative effects of increasing groundwater depth; however, restrictions on this adaptation were exceeded at deeper groundwater depth.