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Abstract It was observed that a super-efficient gel adsorbent system (RRQG@CDC) could be obtained when a matrix material of polyquaternium gel with a flat distribution (RRQG) was loaded onto a skeleton material of cyclodextrin carbide (CDC). The results showed that the adsorption capacity of RRQG@CDC towards dyes was 1250 times higher than that of commonly used activated carbon, enabling highly efficient purification of dyeing wastewater through superior adsorption. In addition, RRQG@CDC demonstrated adaptability to a range of different pH values and salinity conditions, showing super-efficient adsorption abilities towards various types of dyes. Moreover, simulated scale-up tests confirmed the feasibility of this super-efficient adsorbent for practical engineering applications. An enhanced quasi-planar electrostatic adsorption mechanism model was established, which has changed the traditional understanding of adsorption mechanisms. Furthermore, the waste residues of RRQG@CDC, after dye adsorption, can be directly utilized as high-calorific fuels, showcasing the resourcefulness of these residues while eliminating the risk of secondary pollution. In conclusion, this study achieved a remarkably efficient and resource-based purification of dyeing wastewater by developing a highly effective adsorbent system.

Abstract Bursaphelenchus xylophilus (Steiner&Buhrer) Nickle is a global quarantine pest that causes devastating mortality in pine species. The rapid and uncontrollable parasitic spread of this organism results in substantial economic losses to pine forests annually. In this study, we used the MaxEnt model and GIS software ArcGIS10.8 to predict the distribution of B. xylophilus based on collected distribution points and 19 environmental variables (with a correlation coefficient of|R| > 0.8) for the contemporary period (1970–2000), 2041–2060 (2050s), 2061–2080 (2070s), and 2081–2100 (2090s) under four shared socioeconomic pathways (SSPs). We conducted a comprehensive analysis of the key environmental factors affecting the geographical distribution of B. xylophilus and suitable distribution areas. Our results indicate that in current prediction maps B. xylophilus had potential suitable habitats in all continents except Antarctica, with East Asia being the region with the most highly suitable areas and the most serious epidemic area currently. Precipitation of the warmest quarter, temperature seasonality, precipitation of the wettest month, and maximum temperature of the warmest month were identified as key environmental variables that determine the distribution of B. xylophilus. Under future climatic conditions, the potential geographic distribution of B. xylophilus will expand relative to current conditions. In particular, under the SSP5-8.5 scenario in 2081–2100, suitable areas will expand to higher latitudes, and there will be significant changes in suitable areas in Europe, East Asia, and North America. These findings are crucial for future prevention and control management and monitoring.

Abstract Litsea coreana Levl. var. sinensis (Allen) Yang et P. H. Huang is a popular ethnic herb and beverage plant known for its high flavonoid content, which has been linked to a variety of pharmacological benefits and crucial health-promoting impacts in humans. The progress in understanding the molecular mechanisms of flavonoid accumulation in this plant has been hindered due to the deficiency of genomic and transcriptomic resources. We utilized a combination of Illumina and Oxford Nanopore Technology (ONT) sequencing to generate a de novo hybrid transcriptome assembly. In total, 126,977 unigenes were characterized, out of which 107,977 were successfully annotated in seven public databases. Within the annotated unigenes, 3,781 were categorized into 58 transcription factor families. Furthermore, we investigated the presence of four valuable flavonoids—quercetin-3-O-β-D-galactoside, quercetin-3-O-β-D-glucoside, kaempferol-3-O-β-D-galactoside, and kaempferol-3-O-β-D-glucoside in 98 samples, using high-performance liquid chromatography. A weighted gene co-expression network analysis identified two co-expression modules, MEpink and MEturquoise, that showed strong positive correlation with flavonoid content. Within these modules, four transcription factor genes (R2R3-MYB, NAC, WD40, and ARF) and four key enzyme-encoding genes (CHI, F3H, PAL, and C4H) emerged as potential hub genes. Among them, the R2R3-MYB (LcsMYB123) as a homologous gene to AtMYB123/TT2, was speculated to play a significant role in flavonol biosynthesis based on phylogenetic analysis. Our findings provided a theoretical foundation for further research into the molecular mechanisms of flavonoid biosynthesis. Additionally, The hybrid transcriptome sequences will serve as a valuable molecular resource for the transcriptional annotation of L. coreana var. sinensis, which will contribute to the improvement of high-flavonoid materials.

Abstract Osteoporosis, a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture, has led to a high risk of fatal osteoporotic fractures worldwide. Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis, with sex-specific differences in epidemiology and pathogenesis. Specifically, females are more susceptible than males to osteoporosis, while males are more prone to disability or death from the disease. To date, sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells. Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men. This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis, mainly in a population of aging patients, chronic glucocorticoid administration, and diabetes. Moreover, we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men. Additionally, the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

Abstract Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases, which continuously pose one of the most serious threats to human health, attributed to factors such as the emergence of new pathogens, increasing drug resistance, changes in living environments and lifestyles, and the aging population. Despite rapid advancements in mechanistic research and drug development for these diseases, current treatments often have limited efficacy and notable side effects, necessitating the development of more effective and targeted anti-inflammatory therapies. In recent years, the rapid development of nanotechnology has provided crucial technological support for the prevention, treatment, and detection of inflammation-associated diseases. Various types of nanoparticles (NPs) play significant roles, serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and bioavailability. NPs can also directly combat pathogens and inflammation. In addition, nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory diseases. This review categorizes and characterizes different types of NPs, summarizes their applications in the prevention, treatment, and detection of infectious and inflammatory diseases. It also discusses the challenges associated with clinical translation in this field and explores the latest developments and prospects. In conclusion, nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.

Objective: To optimize the enzyme-assisted extraction process of polysaccharides from artificially-cultivated Cordyceps cicadae was conducted in this study. Four different parameters were considered to evaluate the yield of polysaccharides including liquid to solid ratio, enzyme dosage, enzymatic temperature and extraction time. Methods: A four-factor-three-level experimental design was employed to establish a mathematical model by Box-Behnken method, and the scavenging capacity of polysaccharides against three radicals was examined. Afterward, Fick's second law was used to build the kinetic model for the extraction of polysaccharide from artificially-cultivated Cordyceps cicadae. The parameters including rate constants, relative extraction rate, and activation energy were employed to analyze the kinetic and thermodynamic features. Results: Based on the response surface analysis, the optimal extraction process was presented to be as following: Liquid to solid ratio 1:30 g/mL, enzyme dosage 1.6%, enzymatic digestion temperature 67 ℃ and extraction time 90 min. The polysaccharide yield under the above condition was 7.91%, which was close to the predicted value. Moreover, the results of antioxidant capacities indicated that the obtained crude polysaccharides under optimal conditions showed strong DPPH radical scavenging and hydroxyl radical scavenging with IC50 values for 0.60 and 0.54 mg/mL, respectively, and its ORAC value was 45.62 Trolox μmol/g, suggesting potent antioxidant activity in vitro. Conclusion：The study of enzyme-assisted extraction of artificially-cultivated Cordyceps cicadae flower polysaccharides provide theoretical support for the production of polysaccharide fractions from this kind of commercialized Cordyceps cicadae resources.

Hepatitis B is a major global challenge, but there is a lack of epidemiological research on hepatitis B incidence from a change point perspective. This study aimed to fill this gap by identifying significant change points and trends in hepatitis time series in Xinjiang, China. The datasets were obtained from the Xinjiang Information System for Disease Control and Prevention. The Mann-Kendall-Sneyers (MKS) test was used to detect change points and trend changes on the hepatitis B time series of 14 regions in Xinjiang, and the effectiveness of this method was validated by comparing it with the binary segmentation (BS) and segment regression (SR) methods. Based on the results of change point analysis, the prevention and control policies and measures of hepatitis in Xinjiang were discussed. The results showed that 8 regions (57.1%) with at least one change fell within the 95% confidence interval (CI) in all 14 regions by the MKS test, where five regions (Turpan (TP), Hami (HM), Bayingolin (BG), Kyzylsu Kirgiz (KK), Altai (AT)) were identified at one change point, two change points existed for two regions (Aksu (AK), Hotan (HT)) and three change points was detected in 1 region (Bortala (BT)). Most of the change points occurred at both ends of the sequence. More change points indicated an upward trend in the front half of the sequence, while in the latter half, many change points indicated a downward trend prominently. Finally, in comparing the results of the three change point tests, the MKS test showed a 61.5% agreement (8/13) with the BS and SR.

Abstract Activation of the NLRP3 inflammasome is a two-step process: the priming and the activating. The priming step involves the induction of NLRP3 and pro-IL-1β, while the activating step leads to the full inflammasome activation triggered by a NLRP3 activator. Although mechanisms underlying the NLRP3 inflammasome activation have been increasingly clear, the regulation of this process remains incompletely understood. In this study, we find that LPS and Pseudomonas aeruginosa cause a rapid downregulation in MafB transcription in macrophages, which leads to a quick decline in the level of MafB protein because MafB is short-lived and constantly degraded by the ubiquitin/proteasome system. We find that MafB knockdown or knockout markedly enhances the NLRP3, but not the NLRP1, NLRC4, or AIM2, inflammasome activation in macrophages. Conversely, pharmacological induction of MafB diminishes the NLRP3 inflammasome activation. Mechanistically, we find that MafB sustains the expression of p62, a key mediator of autophagy/mitophagy. We find that MafB inhibits mitochondrial damage, and mitochondrial ROS production and DNA cytoplasmic release. Furthermore, we find that myeloid MafB deficient mice demonstrate increased systemic and lung IL-1β production in response to LPS treatment and P. aeruginosa infection and deficient lung P. aeruginosa clearance in vivo. In conclusion, our study demonstrates that MafB is an important negative regulator of the NLRP3 inflammasome. Our findings suggest that strategies elevating MafB may be effective to treat immune disorders due to excessive activation of the NLRP3 inflammasome.

Abstract Plasma cleaning is an effective method for removing micro/nanoparticle particles, thus solving the pollution problem of micro/nanoparticle instruments. However, the lack of research on the phase transition evolution law of micro/nanoparticles under the action of plasma affects the popularization and application of this method and is the key factor that affects the cleaning quality. The focus of this study is to analyze this law. Through experimental observation and finite element simulation, the spatial phase transition distribution characteristics of particles and the influence law of laser parameters are analyzed. Moreover, the effect of the particle phase transition on the cleaning process is discussed. The removal threshold and the best removal area of different particles are presented, and a reference and guidance for the follow-up development of laser-plasma shock wave removal technology are provided.

Background: The investigation of lncRNAs has provided a novel perspective for elucidating mechanisms underlying diverse physiological and pathological processes. Compelling evidence has revealed an intrinsic link between lncRNAs and lipid metabolism, demonstrating that lncRNAs-induced disruption of lipid metabolism and signaling contribute to the development of multiple cancers and some other diseases, including obesity, fatty liver disease, and cardiovascular disease. Aimof Review: The current review summarizes the recent advances in basic research about lipid metabolism and lipid signaling-related lncRNAs. Meanwhile, the potential and challenges of targeting lncRNA for the therapy of cancers and other lipid metabolism-related diseases are also discussed. Key Scientific Concept of Review: Compared with the substantial number of lncRNA loci, we still know little about the role of lncRNAs in metabolism. A more comprehensive understanding of the function and mechanism of lncRNAs may provide a new standpoint for the study of lipid metabolism and signaling. Developing lncRNA-based therapeutic approaches is an effective strategy for lipid metabolism-related diseases.

Camellia atrothea H.T. Chang, H.S. Wang & B.H. Chen 1983 is a native Camellia species in China, which has significant economic and breeding values. Here, we assembled and analyzed the complete chloroplast genome sequence of C. atrothea based on the whole genome sequencing data from Illumina NovaSeq6000 platform. Results show that the complete chloroplast genome of C. atrothea is 157,099 bp in length, and comprises a large single-copy (LSC, 86,643 bp) region, a small single-copy (SSC, 18,276 bp) region, and a pair of inverted repeats (IRs, 26,090 bp) region. Annotation of the C. atrothea chloroplast genome predicts a total of 133 genes, including 88 protein-coding genes, 8 ribosomal RNA genes, and 37 transfer RNA genes. The overall GC content accounts for 37.30% of the genome, which is clearly consistent with that of other previously published Camellia species from section Thea. Phylogenetic analyses of the whole chloroplast genome sequences of 14 Camellia species using Actinidia chinensis as outgroup reveals that C. atrothea has a close relationship with C. leptophylla.

This study aimed to explore the spatio-temporal distribution characteristics and risk factors of hepatitis B (HB) in 14 prefectures of Xinjiang, China, and to provide a relevant reference basis for the prevention and treatment of HB. Based on HB incidence data and risk factor indicators in 14 prefectures in Xinjiang from 2004 to 2019, we explored the distribution characteristics of the risk of HB incidence using global trend analysis and spatial autocorrelation analysis and established a Bayesian spatiotemporal model to identify the risk factors of HB and their spatio-temporal distribution to fit and extrapolate the Bayesian spatiotemporal model using the Integrated Nested Laplace Approximation (INLA) method. There was spatial autocorrelation in the risk of HB and an overall increasing trend from west to east and north to south. The natural growth rate, per capita GDP, number of students, and number of hospital beds per 10, 000 people were all significantly associated with the risk of HB incidence. From 2004 to 2019, the risk of HB increased annually in 14 prefectures in Xinjiang, with Changji Hui Autonomous Prefecture, Urumqi City, Karamay City, and Bayangol Mongol Autonomous Prefecture having the highest rates.

Recent progressions in immunotherapy have transformed cancer treatment, providing a promising strategy that activates the immune system of the patient to find and eliminate cancerous cells. Bispecific antibodies, which engage two separate antigens or one antigen with two distinct epitopes, are of tremendous concern in immunotherapy. The bi-targeting idea enabled by bispecific antibodies (BsAbs) is especially attractive from a medical standpoint since most diseases are complex, involving several receptors, ligands, and signaling pathways. Several research look into the processes in which BsAbs identify different cancer targets such angiogenesis, reproduction, metastasis, and immune regulation. By rerouting cells or altering other pathways, the bispecific proteins perform effector activities in addition to those of natural antibodies. This opens up a wide range of clinical applications and helps patients with resistant tumors respond better to medication. Yet, further study is necessary to identify the best conditions where to use these medications for treating tumor, their appropriate combination partners, and methods to reduce toxicity. In this review, we provide insights into the BsAb format classification based on their composition and symmetry, as well as the delivery mode, focus on the action mechanism of the molecule, and discuss the challenges and future perspectives in BsAb development.

ObjectiveHepatitis B (HB) is a major global challenge, but there has been a lack of epidemiological studies on HB incidence in Xinjiang from a change-point perspective. This study aims to bridge this gap by identifying significant change points and trends.MethodThe datasets were obtained from the Xinjiang Information System for Disease Control and Prevention. Change points were identified using binary segmentation for full datasets and a segmented regression model for five age groups.ResultsThe results showed four change points for the quarterly HB time series, with the period between the first change point (March 2007) and the second change point (March 2010) having the highest mean number of HB reports. In the subsequent segments, there was a clear downward trend in reported cases. The segmented regression model showed different numbers of change points for each age group, with the 30–50, 51–80, and 15–29 age groups having higher growth rates.ConclusionChange point analysis has valuable applications in epidemiology. These findings provide important information for future epidemiological studies and early warning systems for HB.

Abstract The single-nucleotide polymorphism (SNP) of p53, in particular the codon 72 variants, has recently been implicated as a critical regulator in tumor progression. However, the underlying mechanism remains elusive. Here we found that cancer cells carrying codon 72-Pro variant of p53 showed impaired metastatic potential upon serine supplementation. Proteome-wide mapping of p53-interacting proteins uncovered a specific interaction of the codon 72 proline variant (but not p5372R) with phosphoserine aminotransferase 1 (PSAT1). Interestingly, p5372P-PSAT1 interaction resulted in dissociation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) that otherwise bound to p5372P, leading to subsequent nuclear translocation of PGC-1α and activation of oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle. Depletion of PSAT1 restored p5372P-PGC-1α interaction and impeded the OXPHOS and TCA function, resulting in mitochondrial dysfunction and metastasis suppression. Notably, pharmacological targeting the PSAT1-p5372P interaction by aminooxyacetic acid (AOA) crippled the growth of liver cancer cells carrying the p5372P variant in both in vitro and patient-derived xenograft models. Moreover, AOA plus regorafenib, an FDA-proved drug for hepatocellular carcinoma and colorectal cancer, achieved a better anti-tumor effect on tumors carrying the p5372P variant. Therefore, our findings identified a gain of function of the p5372P variant on mitochondrial function and provided a promising precision strategy to treat tumors vulnerable to p5372P-PSAT1 perturbation.

A ternary-weight neural network (TWN) inspired keyword spotting (KWS) processor is proposed to support complicated and variable application scenarios. To achieve high-precision recognition of ten keywords under 5 dB~Clean wide range of background noises, a convolution neural network consists of four convolution layers and four fully connected layers, with modified sparsity-controllable truncated Gaussian approximation-based ternary-weight training is used. End-to-end optimization composed of three techniques is utilized: 1) the stage-by-stage bit-width selection algorithm to optimize the hardware overhead of FFT; 2) the lossy compressed TWN with symmetric kernel training (SKT) and dedicated internal data reuse computation flow; and 3) the error intercompensation approximate addition tree to reduce the computation overhead with marginal accuracy loss. Fabricated in an industrial 22-nm CMOS process, the processor realizes up to ten keywords in real-time recognition under 11 background noise types, with the accuracy of 90.6%@clean and 85.4%@5 dB. It consumes an average power of $3.8 ~\mu \text{W}$ at 250 kHz and the normalized energy efficiency is $2.79\times $ higher than state of the art.

Abstract To address the efficient resourcefulness of papermaking wastewater, this study designed a super-efficient gel material (SGPQG/SGPQ) that could remove over-10-times masses of lignins from wastewater, and subsequently realized the highly-efficient reuse of wastes. The mass of lignin removed by per unit mass of SGPQG/SGPQ was 10,157.71 mg•g-1, i.e., the mass of lignin removed was 10.16 times that of the mass of SGPQG/SGPQ itself, which was 1.23-50.55 times better than the existing similar materials, showing a super-efficient lignin removal ability. Meanwhile, the average lignin removal rate of SGPQG/SGPQ was 1.85-3.34 times higher than those of the pre-products. Moreover, the extended application of SGPQG/SGPQ in the purification of a complex wastewater and a real papermaking wastewater had been also successfully carried out. The mechanism investigations confirmed an integrated skeleton-space effect mechanism, which is the key factor for SGPQG/SGPQ to achieve the super-efficient lignin removal in the purification of papermaking wastewater. In addition, the SGPQG/SGPQ wastes after treating lignins, could be directly used for adsorption treatment of dyeing wastewater, and had 443.9 times adsorption capacity compared to the widely-used activated carbon, demonstrating an efficient resourcefulness reuse.

Abstract Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies. Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses. The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens. We also explore their current status, inherent challenges, and clinical translation potential.

Immune cells are essential for initiating and developing the fibrotic process by releasing cytokines and growth factors that activate fibroblasts and promote extracellular matrix deposition. Immunometabolism describes how metabolic alterations affect the function of immune cells and how inflammation and immune responses regulate systemic metabolism. The disturbed immune cell function and their interactions with other cells in the tissue microenvironment lead to the origin and advancement of fibrosis. Understanding the dysregulated metabolic alterations and interactions between fibroblasts and the immune cells is critical for providing new therapeutic targets for fibrosis. This review provides an overview of recent advances in the pathophysiology of fibrosis from the immunometabolism aspect, highlighting the altered metabolic pathways in critical immune cell populations and the impact of inflammation on fibroblast metabolism during the development of fibrosis. We also discuss how this knowledge could be leveraged to develop novel therapeutic strategies for treating fibrotic diseases.

Abstract Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice.

Abstract Background Hypoxia, a typical hallmark of solid tumors, exhibits an essential role in the progression of colorectal cancer (CRC), in which the dysregulation of long non-coding RNAs (lncRNAs) is frequently observed. However, the underlying mechanisms are not clearly defined. Methods The TCGA database was analyzed to identify differential lncRNA expression involved in hypoxia-induced CRC progression. qRT-PCR was conducted to validate the upregulation of lncRNA STEAP3-AS1 in CRC cell lines and tumor-bearing mouse and zebrafish models under hypoxia. ChIP-qRT-PCR was used to detect the transcriptional activation of STEAP3-AS1 mediated by HIF-1α. RNA-seq, fluorescent in situ hybridization, RNA pulldown, RNA immunoprecipitation, co-immunoprecipitation, immunofluorescence and immunoblot experiments were used to ascertain the involved mechanisms. Functional assays were performed in both in vitro and in vivo models to investigate the regulatory role of STEAP3-AS1/STEAP3/Wnt/β-catenin axis in CRC proliferation and metastasis. Results Here, we identified a hypoxia-induced antisense lncRNA STEAP3-AS1 that was highly expressed in clinical CRC tissues and positively correlated with poor prognosis of CRC patients. Upregulation of lncRNA STEAP3-AS1, which was induced by HIF-1α-mediated transcriptional activation, facilitated the proliferation and metastasis of CRC cells both in vitro and in vivo. Mechanistically, STEAP3-AS1 interacted competitively with the YTH domain-containing family protein 2 (YTHDF2), a N6-methyladenosine (m6A) reader, leading to the disassociation of YTHDF2 with STEAP3 mRNA. This effect protected STEAP3 mRNA from m6A-mediated degradation, enabling the high expression of STEAP3 protein and subsequent production of cellular ferrous iron (Fe2+). Increased Fe2+ levels elevated Ser 9 phosphorylation of glycogen synthase kinase 3 beta (GSK3β) and inhibited its kinase activity, thus releasing β-catenin for nuclear translocation and subsequent activation of Wnt signaling to support CRC progression. Conclusions Taken together, our study highlights the mechanisms of lncRNA STEAP3-AS1 in facilitating CRC progression involving the STEAP3-AS1/STEAP3/Wnt/β-catenin axis, which may provide novel diagnostic biomarkers or therapeutic targets to benefit CRC treatment. Graphical abstract Hypoxia-induced HIF-1α transcriptionally upregulates the expression of lncRNA STEAP3-AS1, which interacts competitively with YTHDF2, thus upregulating mRNA stability of STEAP3 and consequent STEAP3 protein expression. The enhanced STEAP3 expression results in production of cellular ferrous iron (Fe2+), which induces the Ser 9 phosphorylation and inactivation of GSK3β, releasing β-catenin for nuclear translocation and contributing to subsequent activation of Wnt signaling to promote CRC progression.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

As a core component in intelligent edge computing, deep neural networks (DNNs) will increasingly play a critically important role in addressing the intelligence-related issues in the industry domain, like smart factories and autonomous driving. Due to the requirement for a large amount of storage space and computing resources, DNNs are unfavorable for resource-constrained edge computing devices, especially for mobile terminals with scarce energy supply. Binarization of DNN has become a promising technology to achieve a high performance with low resource consumption in edge computing. Field-programmable gate array (FPGA)-based acceleration can further improve the computation efficiency to several times higher compared with the central processing unit (CPU) and graphics processing unit (GPU). This paper gives a brief overview of binary neural networks (BNNs) and the corresponding hardware accelerator designs on edge computing environments, and analyzes some significant studies in detail. The performances of some methods are evaluated through the experiment results, and the latest binarization technologies and hardware acceleration methods are tracked. We first give the background of designing BNNs and present the typical types of BNNs. The FPGA implementation technologies of BNNs are then reviewed. Detailed comparison with experimental evaluation on typical BNNs and their FPGA implementation is further conducted. Finally, certain interesting directions are also illustrated as future work.

ObjectiveThe objective of this study was to investigate the spatio-temporal distribution and epidemiological characteristics of hepatitis B in 96 districts and counties of Xinjiang and to give useful information for hepatitis B prevention and treatment.MethodsBased on the incidence data of hepatitis B in 96 districts and counties of Xinjiang from 2006 to 2019, the global trend analysis method was used to characterize the spatial variability of the disease, and the spatial autocorrelation and spatio-temporal aggregation analysis were used to explore the spatial clustering of hepatitis B and to identify high-risk areas and periods. The Integrated Nested Laplace Approximation (INLA)-based spatial age-period-cohort model was established to further explore the influence of age, period, birth queue effect, and spatial distribution on the incidence risk of hepatitis B, and sum-to-zero constraint was adopted to avoid the issue of model unrecognition.ResultsThe risk of hepatitis B in Xinjiang is increasing from west to east and from north to south, with spatial heterogeneity and spatio-temporal scanning statistics yielding five clustering areas. The spatial age-period-cohort model showed two peaks in the average risk of hepatitis B, at [25,30) years old and [50,55) years old, respectively. The mean risk of hepatitis B incidence fluctuated up and down around 1 with time, and the average risk of disease by birth cohort displayed an increasing-decreasing-stabilizing trend. Taking age, period, and cohort effect into consideration, it was found that the areas with a high risk of hepatitis B are Tianshan District, Xinshi District, Shuimogou District, Changji City, Aksu City, Kashi City, Korla City, Qiemo County and Yopurga County in Xinjiang. According to the spatio-temporal effect item, it was found that there are unobserved variables affecting the incidence of hepatitis B in some districts and counties of Xinjiang.ConclusionThe spatio-temporal characteristics of hepatitis B and the high-risk population needed to be taken into attention. It is suggested that the relevant disease prevention and control centers should strengthen the prevention and control of hepatitis B among young people while paying attention to middle-aged and older adult people, and strengthening the prevention and monitoring of high-risk areas.

Abstract The design of the efficient, flexible air electrode for enhancing the Zn‐air batteries (ZABs) performance is vital in developing a new portable rechargeable power supply. Emerging research indicates that non‐precious metal materials have promising activity for oxygen reduction/evolution in alkaline conditions while constructing a high‐performance and reliable electrode is still a big challenge at the present stage. In this work, a bimetal doped zeolitic imidazolate framework (ZIF) film is synthesized by fast current‐driven synthesis (FCDS) on a thin carbon nanotube film (CNTF). After carbonization at 950 °C, CoFe‐N‐C nanofoam formed on the CNTF, resulting in binder‐free, flexible electrodes. It exhibits excellent activity and stability toward oxygen reduction and evolution. The CoFe‐N‐C/CNTF‐based liquid‐state ZAB shows an output power density of 294 mW cm−2. When applied in solid‐state ZAB, the flexible battery shows high power density and excellent cycling stability.

Abstract Background Phoebe zhennan S.Lee (nanmu) is listed as a threatened tree species in China, whose growth and development, especially during the seedling stage, can be severely limited by drought. Previous studies on nanmu responses to drought stress involved physiological and biochemical analyses, while the molecular mechanisms remained unclear. Therefore, it is of great significance to carry out molecular biology research on the drought resistance of nanmu and reveal the genetic background and molecular regulation mechanism of nanmu drought resistance. Results Drought stress enhanced the soluble sugar (SS), free proline(PRO), superoxide anion (O2·−), and hydrogen peroxide (H2O2) contents as well as the peroxidase (POD) and monodehydroascorbate reductase (MDHAR) activities of nanmu. However, glutathione S-transferase (GST) activity was sensitive to drought stress. Further transcriptomic and proteomic analyses revealed the abundant members of the differentially expressed genes(DEGs) and differentially expressed proteins(DEPs) that were related to phenylpropanoid and flavonoid biosynthesis, hormone biosynthesis and signal transduction, chlorophyll metabolism, photosynthesis, and oxidation-reduction reaction, which suggested their involvement in the drought response of nanmu. These enhanced the osmotic regulation, detoxification, and enzyme-induced and non-enzyme-induced antioxidant ability of nanmu. Moreover, 52% (447/867) of proteins that were up-regulated and 34% (307/892) down-regulated ones were attributed to the increase and decrease of transcription abundance. Transcript up (TU) and protein up (PU) groups had 447 overlaps, while transcript down (TD) and protein down (PD) groups had 307 overlaps, accounting for 54% of up and 35% of down-regulated proteins. The lack of overlap between DEGs and DEPs also suggested that post-transcriptional regulation has a critical role in nanmu response to drought. Conclusions Our research results provide significant insights into the regulatory mechanisms of drought stress in nanmu.

Abstract Metformin, a well‐known antidiabetic drug, has been repurposed for cancer treatment; however, recently observed drug resistance and tumor metastasis have questioned its further application. Here, we found that long‐term metformin exposure led to metabolic adaptation of hepatocellular carcinoma (HCC) cells, which was characterized by an obvious epithelial–mesenchymal transition (EMT) phenotype and compensatory elevation of oxidative phosphorylation (OXPHOS). TOMM34, a translocase of the outer mitochondrial membrane, was upregulated to promote tumor metastasis in response to metformin‐induced metabolic stress. Mechanistically, TOMM34 interacted with ATP5B to preserve F1FO‐ATPase activity, which conferred mitochondrial OXPHOS and ATP production. This metabolic preference for OXPHOS suggested a large requirement of energy supply by cancer cells to survive and spread in response to therapeutic stress. Notably, disturbing the interaction between TOMM34 and ATP5B using Gboxin, a specific OXPHOS inhibitor, increased sensitivity to metformin and suppressed tumor progression both in vitro and in vivo. Overall, this study demonstrates a molecular link of the TOMM34/ATP5B‐ATP synthesis axis during metformin adaptation and provides promising therapeutic targets for metformin sensitization in cancer treatment.

Dietary carbohydrates are unexploited in the by-products of economically valuable Phyllostachys pracecox bamboo shoots. A residue-derived polysaccharide (PBSR1) was aqueously extracted from the processing waste of this bamboo shoot species. Its primary structure and advanced conformation were elucidated by a combined analysis of spectroscopy, chromatography, 2D nuclear magnetic resonance, laser light scattering and atomic microscopy. The results indicated PBSR1 was a triple-helix galactan consisting of →6)-β-D-Galp and →3)-β-D-Galp in linear with an 863 KD molecular weight (Mw). The relationship between the radius of gyration (Rg) and intrinsic viscosity ([η]) on Mw were established as Rg = 1.95 × 10−2Mw0.52±0.03 (nm) and [η] = 9.04 × 10−1Mw0.56±0.02 (mL/g) for PBSR1 in saline solution at 25 °C, which indicated it adopted a triple-helix chain shape with a height of 1.60 ± 0.12 nm supported by a red shift of λmax in Congo red analysis. The thermodynamic test (TG) displayed that it had excellent thermal stability for the food industry. Further, those unique structure features furnish PBSR1 on antioxidation with EC50 of 0.65 mg/mL on DPPH· and an ORAC value of 329.46 ± 12.1 μmol TE/g. It also possessed pronounced immunostimulation by up-regulating pro-inflammatory signals including NO, IL-6, TNF-α and IL-1β in murine cells. Our studies provided substantial data for the high-valued application of residues and a better understanding of the structure–function relationship of polysaccharide.

Abstract Purines and their derivatives, most notably adenosine and ATP, are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis. Besides, these purines support, as chemical messengers, purinergic transmission throughout tissues and species. Purines act as endogenous ligands that bind to and activate plasmalemmal purinoceptors, which mediate extracellular communication referred to as “purinergic signalling”. Purinergic signalling is cross-linked with other transmitter networks to coordinate numerous aspects of cell behaviour such as proliferation, differentiation, migration, apoptosis and other physiological processes critical for the proper function of organisms. Pathological deregulation of purinergic signalling contributes to various diseases including neurodegeneration, rheumatic immune diseases, inflammation, and cancer. Particularly, gout is one of the most prevalent purine-related disease caused by purine metabolism disorder and consequent hyperuricemia. Compelling evidence indicates that purinoceptors are potential therapeutic targets, with specific purinergic agonists and antagonists demonstrating prominent therapeutic potential. Furthermore, dietary and herbal interventions help to restore and balance purine metabolism, thus addressing the importance of a healthy lifestyle in the prevention and relief of human disorders. Profound understanding of molecular mechanisms of purinergic signalling provides new and exciting insights into the treatment of human diseases.

Objective: Cantleyoside (CA) is a kind of iridoid glycosides in Pterocephalus hookeri (C. B. Clarke) Höeck. The purpose of this study was to investigate the effects of CA on human rheumatoid arthritis fibroblast synovial cells (HFLS-RA). Methods: Cell proliferation of HFLS-RA was assessed by CCK-8. ELISA was used to detect cytokines NO, TNF-α, IL-1β/6, MCP-1, MMP-1/3/9 and metabolism-related ATPase activities and ATP levels. JC-1, DCFH-DA, Fluo-3 AM and Calcein AM probes were used to detect mitochondrial membrane potential (MMP), reactive oxygen species (ROS), Ca2+ and mitochondrial permeability conversion pore (MPTP), respectively. Isolated mitochondria assay was used to detect mitochondrial swelling. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and real-time ATP production were measured using a Seahorse analyzer. Apoptosis was detected by TUNEL and Hoechst staining. Western blot was used to detect the expressions of AMPK/p-AMPK, Sirt 1, IκBα, NF-κB p65/p-NF-κB p65, Bcl-2 and Bax. Cytoplasmic nuclear isolation was also performed to detect the translocation of NF-κB. Results: CA significantly suppressed cell proliferation and the levels of NO, TNF-α, IL-1β/6, MCP-1 and MMP-1/3/9 in HFLS-RA. In addition, CA promoted the apoptosis of HFLS-RA by increasing TUNEL and Hoechst positive cells and the ratio of Bax/Bcl-2. Inhibition of energy metabolism in HFLS-RA by CA reduced OCR, ECAR and real-time ATP generation rate. Importantly, CA promoted p-AMPK and Sirt 1 expression, inhibited IκBα degradation to reduce p-NF-κB and translocation. Conclusion: The results suggest that CA activates the AMPK/Sirt 1/NF-κB pathway by promoting mitochondrial dysfunction, thereby exerting anti-inflammatory and pro-apoptotic effects.

Chilling stress threatens the yield and distribution pattern of global crops, including the tea plant (Camellia sinensis), one of the most important cash crops around the world. Circular RNA (circRNA) plays roles in regulating plant growth and biotic/abiotic stress responses. Understanding the evolutionary characteristics of circRNA and its feedbacks to chilling stress in the tea plant will help to elucidate the vital roles of circRNAs. In the current report, we systematically identified 2702 high-confidence circRNAs under chilling stress in the tea plant, and interestingly found that the generation of tea plant circRNAs was associated with the length of their flanking introns. Repetitive sequences annotation and DNA methylation analysis revealed that the longer flanking introns of circRNAs present more repetitive sequences and higher methylation levels, which suggested that repeat-elements-mediated DNA methylation might promote the circRNAs biogenesis in the tea plant. We further detected 250 differentially expressed circRNAs under chilling stress, which were functionally enriched in GO terms related to cold/stress responses. Constructing a circRNA-miRNA-mRNA interaction network discovered 139 differentially expressed circRNAs harboring potential miRNA binding sites, which further identified 14 circRNAs that might contribute to tea plant chilling responses. We further characterized a key circRNA, CSS-circFAB1, which was significantly induced under chilling stress. FISH and silencing experiments revealed that CSS-circFAB1 was potentially involved in chilling tolerance of the tea plant. Our study emphasizes the importance of circRNA and its preliminary role against low-temperature stress, providing new insights for tea plant cold tolerance breeding.