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Abstract Background Baryscapus dioryctriae (Chalcidodea: Eulophidae) is a parasitic wasp that parasitizes the pupae of many Pyralidae members and has been used as a biological control agent against Dioryctria pests of pinecones. Results This B. dioryctriae assembly has a genome size of 485.5 Mb with a contig N50 of 2.17 Mb, and scaffolds were assembled onto six chromosomes using Hi-C analysis, significantly increasing the scaffold N50 to 91.17 Mb, with more than 96.13% of the assembled bases located on chromosomes, and an analysis revealed that 94.73% of the BUSCO gene set. A total of 54.82% (279.27 Mb) of the assembly was composed of repetitive sequences and 24,778 protein-coding genes were identified. Comparative genomic analysis demonstrated that the chemosensory perception, genetic material synthesis, and immune response pathways were primarily enriched in the expanded genes. Moreover, the functional characteristics of an odorant-binding protein (BdioOBP45) with ovipositor-biased expression identified from the expanded olfactory gene families were investigated by the fluorescence competitive binding and RNAi assays, revealing that BdioOBP45 primarily binds to the D. abietella-induced volatile compounds, suggesting that this expanded OBP is likely involved in locating female wasp hosts and highlighting a direction for future research. Conclusions Taken together, this work not only provides new genomic sequences for the Hymenoptera systematics, but also the high-quality chromosome-level genome of B. dioryctriae offers a valuable foundation for studying the molecular, evolutionary, and parasitic processes of parasitic wasps.

Abstract Background Haem is essential but toxic for metazoan organisms. Auxotrophic nematodes can acquire sufficient haem from the environment or their hosts in the meanwhile eliminate or detoxify excessive haem through tightly controlled machinery. In previous work, we reported a role of the unique transporter protein HRG-1 in the haem acquisition and homeostasis of parasitic nematodes. However, little is known about the haem efflux and detoxification via ABC transporters, particularly the multiple drug resistance proteins (MRPs). Results Here, we further elucidate that a member of the mrp family (mrp-3) is involved in haem efflux and detoxification in a blood-feeding model gastrointestinal parasite, Haemonchus contortus. This gene is haem-responsive and dominantly expressed in the intestine and inner membrane of the hypodermis of this parasite. RNA interference of mrp-3 resulted in a disturbance of genes (e.g. hrg-1, hrg-2 and gst-1) that are known to be involved in haem homeostasis and an increased formation of haemozoin in the treated larvae and lethality in vitro, particularly when exposed to exogenous haem. Notably, the nuclear hormone receptor NHR-14 appears to be associated the regulation of mrp-3 expression for haem homeostasis and detoxification. Gene knockdown of nhr-14 and/or mrp-3 increases the sensitivity of treated larvae to exogenous haem and consequently a high death rate (> 80%). Conclusions These findings demonstrate that MRP-3 and the associated molecules are essential for haematophagous nematodes, suggesting novel intervention targets for these pathogens in humans and animals.

Strong-aroma natural spices are characterized by their strong aroma, possessing aromatic and irritating properties, with the main components being aromatic compounds. Typical representatives include star anise, cinnamon, fennel, and cloves. The aforementioned strong-aroma natural spices are widely used both domestically and internationally, especially in soy sauce stewed meat products and fermented meat products. Nonetheless, current research on the aroma-imparting and flavor-presenting mechanisms of natural spices remains insufficiently in-depth and systematic. This paper bases on a review of relevant domestic and international research in recent years, systematically summarizes the flavor analysis methods, flavor characteristics, and key flavor components of typical strong-aroma natural spices. It concurrently discusses their impact on the flavor formation of meat products: spice flavor components can influence the flavor of soy sauce stewed meat products by directly migrating into the food or by improving the flavor of fermented meat products through inhibiting fat oxidation and anti-bacterial effects. Building on this, the paper further elucidates the aroma-imparting and flavor-presenting mechanisms of strong-aroma natural spices, encompassing direct migration of flavor components into food for aroma enhancement, aroma-generating reactions between spice components and food matrices, inhibition of flavor precursor oxidation processes, and suppression of spoilage bacteria growth to ameliorate undesirable flavor formation. The summary of the flavor characteristics and aroma-imparting mechanisms of strong-aroma natural spices facilitates researchers in delving into the mechanisms by which these spices regulates food flavor formation and provides a reference for food enterprises, particularly meat product manufacturers, in further rational development and utilization of natural spices.

Abstract Background Chlorophenoxy compounds represent a group of selective herbicides widely used around the world. Chlorophenoxy herbicides are toxic, chemically stable, and can migrate into groundwater through soil leaching, posing a significant threat to drinking water safety and human health. Chlorophenoxy herbicides in groundwater aquifers are subject to anaerobic processes; however, the pathway and microbiology involved in the attenuation of chlorophenoxy herbicides under anaerobic condition are largely unknown. Here, the anaerobic degradation process of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a typical chlorophenoxy herbicide, was investigated. Results The initial 52.5 ± 2.3 μM 2,4,5-T was completely degraded by a sediment-derived microbial consortium, with 3,4-dichlorophenol, 2,5-dichlorophenol, 3-chlorophenol (3-CP) and phenol being identified as the intermediate products. Reductive dechlorination of 3-CP to phenol and the subsequent elimination of phenol were the key transformation steps in the overall degradation process of 2,4,5-T. Amplicon sequencing suggested that Dehalobacter, Sulfuricurvum, Bacteroides, Acetobacterium, and Clostridium sensu stricto 7 might contribute to the transformation of 2,4,5-T to phenol, and Smithella, Syntrophorhabdus, Methanofollis and Methanosaeta likely cooperated to accomplish the complete mineralization of phenol. Conclusions This study reported the anaerobic degradation of 2,4,5-T via reductive dechlorination and the subsequent syntrophic metabolization of phenol, an intermediate product transformed from 2,4,5-T. Dehalobacter was identified as the organohalide-respiring population catalyzing the reductive dechlorination reaction. Syntrophorhabdus and methanogenic populations were likely involved in anaerobic phenol oxidation and facilitated the complete mineralization of 2,4,5-T.

Abstract Intervertebral disc degeneration (IDD) is a major cause of discogenic pain, and is attributed to the dysfunction of nucleus pulposus, annulus fibrosus, and cartilaginous endplate (CEP). Osteopontin (OPN), a glycoprotein, is highly expressed in the CEP. However, little is known on how OPN regulates CEP homeostasis and degeneration, contributing to the pathogenesis of IDD. Here, we investigate the roles of OPN in CEP degeneration in a mouse IDD model induced by lumbar spine instability and its impact on the degeneration of endplate chondrocytes (EPCs) under pathological conditions. OPN is mainly expressed in the CEP and decreases with degeneration in mice and human patients with severe IDD. Conditional Spp1 knockout in EPCs of adult mice enhances age-related CEP degeneration and accelerates CEP remodeling during IDD. Mechanistically, OPN deficiency increases CCL2 and CCL5 production in EPCs to recruit macrophages and enhances the activation of NLRP3 inflammasome and NF-κB signaling by facilitating assembly of IRAK1-TRAF6 complex, deteriorating CEP degeneration in a spatiotemporal pattern. More importantly, pharmacological inhibition of the NF-κB/NLRP3 axis attenuates CEP degeneration in OPN-deficient IDD mice. Overall, this study highlights the importance of OPN in maintaining CEP and disc homeostasis, and proposes a promising therapeutic strategy for IDD by targeting the NF-κB/NLRP3 axis.

Background: As a physiological function of body, immunity can maintain health by identifying itself and excluding others. With economic development and increasingly fierce social competition, the number of sub-healthy population is gradually increasing, and the most basic problem exposed is human hypoimmunity. Hypoimmunity can be manifested as often feeling tired, catching colds, mental depression, etc. In order to enhance immunity, eating healthy foods with the effect of enhancing immunity may become an effective choice. KRG has pharmacological effects of enhancing immunity. Because the screening and evaluation method of immune population are not unified, there are relatively few KRG immunity tests for sub-health population. It is of great significance to study the effect of KRG on people with hypoimmunity to improve sub-health status. Methods: This was a 180-day, randomized, double-blind, placebo-controlled clinical trial. According to the trial scheme design, 119 qualified subjects were included and randomly divided into the test group taking KRG and the placebo control group. Subjects need to check safety indicators (blood pressure and heart rate, blood routine, liver and kidney function, urine routine and stool routine) and efficacy indicators (main and secondary) inspection at baseline, efficacy indicators inspection during the mid-term of the test (90th days of administration), safety and efficacy indicators inspection after the test (180th days of administration). Results: After the test, the safety indicators of placebo control group and KRG test group were basically within the normal range, and there is no significant difference in fireness score between the two groups. Through follow-up interviews, it was found that the subjects in the test group and the control group had no adverse reactions and allergic reactions such as nausea, flatulence, diarrhea, and abdominal pain during the test period. Self-comparison of the test group, the results of the main efficacy indicators: (1) immune related health scores were significantly improved in the mid-term and after the test (P

Abstract Background Data on long-term cancer survivors treated with apatinib are lacking. This study aimed to describe the characteristics of long-term cancer survivors after apatinib-based therapy, and to know about their satisfaction degree with apatinib and severity of depression and insomnia. Methods Patients with solid tumors who had received apatinib-based therapy for at least 5 years were invited to complete an online questionnaire. Characteristics of patients and treatment, knowledge of apatinib, satisfaction degree, and severity of depression and insomnia assessed by Patient Health Questionnaire-9 and Insomnia Severity Index were collected. Results Between December 8, 2023 and March 1, 2024, a total of 436 patients completed the online questionnaire. Most patients were satisfied with the efficacy (96.6%) and safety (93.1%) of apatinib, were willing to continue apatinib treatment (99.5%), and would recommend apatinib to other patients (93.3%). Continuous apatinib treatment resulted in significant negative impact on daily life, work, or study in only two (0.5%) patients. Almost all patients currently had no or mild depression (97.0%) and insomnia (97.9%) problems. The most common patient-reported adverse events were hand-foot syndrome (21.3%) and hypertension (18.3%). Conclusions Our survey showed a high satisfaction degree with apatinib in long-term cancer survivors. Long-term apatinib treatment resulted in almost no negative impact on patient’s quality of life.

Abstract Variations at the event horizon structure of a black hole will emit the signals of the gravitational wave echoes associated with the ringdown of the binary black hole merger. In this work, combining mass model of M87 and Einasto profile for dark matter halo, we construct one formal solution of black holes in dark matter halo, and this solution includes the regular black hole for geometric parameter $$a < 2M$$ a < 2 M and the wormhole for $$a \ge 2M$$ a ≥ 2 M . Then, we test this solution under axial gravitational perturbation and calculate their quasinormal modes (QNM). Our results show that when geometric parameter $$a>2M$$ a > 2 M , a series of gravitational wave echoes appear after the QNM, and one distinctive feature of gravitational wave echoes is the double barrier. Besides, we also study the impacts of shape parameters $$\alpha $$ α of Einasto profile both on the QNM and gravitational wave echoes, and extract their frequencies using WKB method and Prony method. In principle, with the increasing of shape parameter $$\alpha $$ α , the frequencies of the QNM and gravitational wave echoes between the different shape parameters must be different. But now there is zero difference of the frequencies between shape parameter $$\alpha =0.18$$ α = 0.18 and $$\alpha =0.20$$ α = 0.20 . Zero difference is not allowed, so we give an upper limit for shape parameter $$\alpha $$ α , which is approximately $$\alpha

Abstract Background Human hexokinase 2 (HK2) plays an important role in regulating Warburg effect, which metabolizes glucose to lactate acid even in the presence of ample oxygen and provides intermediate metabolites to support cancer cell proliferation and tumor growth. HK2 overexpression has been observed in various types of cancers and targeting HK2-driven Warburg effect has been suggested as a potential cancer therapeutic strategy. Given that epigenetic enzymes utilize metabolic intermediates as substrates or co-factors to carry out post-translational modification of histones and nucleic acids modifications in cells, we hypothesized that altering HK2 expression could impact the epigenome and, consequently, chromatin stability in yeast. To test this hypothesis, we established genetic models with different yeast hexokinase 2 (HXK2) expression in Saccharomyces cerevisiae yeast cells and investigated the effect of HXK2-dependent metabolism on parental nucleosome transfer, a key DNA replication–coupled epigenetic inheritance process, and chromatin stability. Results By comparing the growth of mutant yeast cells carrying single deletion of hxk1Δ, hxk2Δ, or double-loss of hxk1Δ hxk2Δ to wild-type cells, we firstly confirmed that HXK2 is the dominant HXK in yeast cell growth. Surprisingly, manipulating HXK2 expression in yeast, whether through overexpression or deletion, had only a marginal impact on parental nucleosome assembly, but a noticeable trend with decrease chromatin instability. However, targeting yeast cells with 2-deoxy-D-glucose (2-DG), a clinical glycolysis inhibitor that has been proposed as an anti-cancer treatment, significantly increased chromatin instability. Conclusion Our findings suggest that in yeast cells lacking HXK2, alternative HXKs such as HXK1 or glucokinase 1 (GLK1) play a role in supporting glycolysis at a level that adequately maintains epigenomic stability. While our study demonstrated an increase in epigenetic instability with 2-DG treatment, the observed effect seemed to occur dependent on non-glycolytic function of Hxk2. Thus, additional research is needed to identify the molecular mechanism through which 2-DG influences chromatin stability.

Abstract Lymph node metastasis (LNM) is a common invasive feature of hepatocellular carcinoma (HCC) associated with poor clinical outcomes. Through microarray profiling and bioinformatic analyses, we identified the circ-0044539-miR-29a-3p-VEGFA axis as a potential key factor in the progression of HCC LNM. In HCC cells and nude mice, circ-0044539 downregulation or miR-29a-3p upregulation was associated with small tumor size, PI3K-AKT-mTOR pathway inactivation, and downregulation of the key LNM factors (HIF-1α and CXCR4). Furthermore, circ-0044539 was also responsible for exosomal miR-29a-3p secretion. Exosomal miR-29a-3p was then observed to migrate to the LNs and downregulate High-mobility group box transcription factor 1 (Hbp1) in Polymorphonuclear Myeloid-derived suppressor cells (PMN-MDSCs), inducing the formation of a microenvironment suitable for tumor colonization. Overall, circ-0044539 promotes HCC cell LNM abilities and induces an immune-suppressive environment in LNs through exosomes, highlighting its potential as a target for HCC LNM and HCC immunotherapy.

Abstract Background Carbon monoxide (CO), hypothetically linked to prebiotic biosynthesis and possibly the origin of the life, emerges as a substantive growth substrate for numerous microorganisms. In anoxic environments, the coupling of CO oxidation with hydrogen (H2) production is an essential source of electrons, which can subsequently be utilized by hydrogenotrophic bacteria (e.g., organohalide-respring bacteria). While Dehalococcoides strains assume pivotal roles in the natural turnover of halogenated organics and the bioremediation of chlorinated ethenes, relying on external H2 as their electron donor and acetate as their carbon source, the synergistic dynamics within the anaerobic microbiome have received comparatively less scrutiny. This study delves into the intriguing prospect of CO serving as both the exclusive carbon source and electron donor, thereby supporting the reductive dechlorination of trichloroethene (TCE). Results The metabolic pathway involved anaerobic CO oxidation, specifically the Wood-Ljungdahl pathway, which produced H2 and acetate as primary metabolic products. In an intricate microbial interplay, these H2 and acetate were subsequently utilized by Dehalococcoides, facilitating the dechlorination of TCE. Notably, Acetobacterium emerged as one of the pivotal collaborators for Dehalococcoides, furnishing not only a crucial carbon source essential for its growth and proliferation but also providing a defense against CO inhibition. Conclusions This research expands our understanding of CO’s versatility as a microbial energy and carbon source and unveils the intricate syntrophic dynamics underlying reductive dechlorination. Graphical Abstract Video Abstract

Abstract Background Stroke is a globally dangerous disease capable of causing irreversible neuronal damage with limited therapeutic options. Meldonium, an inhibitor of carnitine-dependent metabolism, is considered an anti-ischemic drug. However, the mechanisms through which meldonium improves ischemic injury and its potential to protect neurons remain largely unknown. Methods A rat model with middle cerebral artery occlusion (MCAO) was used to investigate meldonium’s neuroprotective efficacy in vivo. Infarct volume, neurological deficit score, histopathology, neuronal apoptosis, motor function, morphological alteration and antioxidant capacity were explored via 2,3,5-Triphenyltetrazolium chloride staining, Longa scoring method, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, rotarod test, transmission electron microscopy and Oxidative stress index related kit. A primary rat hippocampal neuron model subjected to oxygen–glucose deprivation reperfusion was used to study meldonium’s protective ability in vitro. Neuronal viability, mitochondrial membrane potential, mitochondrial morphology, respiratory function, ATP production, and its potential mechanism were assayed by MTT cell proliferation and cytotoxicity assay kit, cell-permeant MitoTracker® probes, mitochondrial stress, real-time ATP rate and western blotting. Results Meldonium markedly reduced the infarct size, improved neurological function and motor ability, and inhibited neuronal apoptosis in vivo. Meldonium enhanced the morphology, antioxidant capacity, and ATP production of mitochondria and inhibited the opening of the mitochondrial permeability transition pore in the cerebral cortex and hippocampus during cerebral ischemia–reperfusion injury (CIRI) in rats. Additionally, meldonium improved the damaged fusion process and respiratory function of neuronal mitochondria in vitro. Further investigation revealed that meldonium activated the Akt/GSK-3β signaling pathway to inhibit mitochondria-dependent neuronal apoptosis. Conclusion Our study demonstrated that meldonium shows a neuroprotective function during CIRI by preserving the mitochondrial function, thus prevented neurons from apoptosis.

Abstract Background Venoms have repeatedly evolved over 100 occasions throughout the animal tree of life, making them excellent systems for exploring convergent evolutionary novelty. Growing evidence supports that venom evolution is predominantly driven by prey or host-related selection pressures, and the expression patterns of venom glands reflect adaptive evolution. However, it remains elusive whether the evolution of expression patterns in venom glands is likewise a convergent evolution driven by their prey/host species. Results We utilized parasitoid wasps that had independently adapted to Drosophila hosts as models to investigate the convergent evolution of venom gland transcriptomes in 19 hymenopteran species spanning ~ 200 million years of evolution. Comparative transcriptome analysis reveals that the global expression patterns among the venom glands of Drosophila parasitoid wasps do not achieve higher similarity compared to non-Drosophila parasitoid wasps. Further evolutionary analyses of expression patterns at the single gene, orthogroup, and Gene Ontology (GO) term levels indicate that some orthogroups/GO terms show correlation with the Drosophila parasitoid wasps. However, these groups rarely include genes highly expressed in venom glands or putative venom genes in the Drosophila parasitoid wasps. Conclusions Our study suggests that convergent evolution may not play a predominant force shaping gene expression levels in the venom gland of the Drosophila parasitoid wasps, offering novel insights into the co-evolution between venom and prey/host.

Abstract Background The effect of nirmatrelvir/ritonavir on preventing post-COVID condition (PCC) in the BA4, BA5, and XBB Omicron predominant periods is not well understood. The purpose of this study was to assess how nirmatrelvir/ritonavir treatment affected both PCC and health-related quality of life. Methods This retrospective cohort study enrolled 2,524 adults aged 18 years and older who were eligible for nirmatrelvir/ritonavir between July 14 to November 14, 2022. All outcomes were observed from the patient’s first visit to the primary health clinic, 1 week, 1 month, 3 months, and 6 months after testing positive for COVID-19. The primary outcome was the presence of PCC. Secondary outcomes included the effects on health-related quality of life, such as walking, bathing and dressing, activities, cause adverse emotions or signs that prevent individuals from leading normal lives over a 180-day observation period. Results There were no significant differences observed between the nirmatrelvir/ritonavir and those not administered (control group) in terms of PCC symptoms at 3 months (OR 0.71 95% CI 0.31, 1.64) and 6 months (OR 1.30 95% CI 0.76, 2.21). At 3 months, the use of nirmatrelvir/ritonavir was associated with a 26% reduction in symptoms causing negative emotions (OR 0.74 95% CI 0.60, 0.92) and an increased likelihood of symptoms limiting walking (OR 1.58 95% CI 1.10, 2.27). However, there were no significant differences between the nirmatrelvir/ritonavir and the control group in terms of the impact of PCC on health-related quality of life at 6 months. Conclusions Our study indicates that the administration of nirmatrelvir/ritonavir does not significantly reduce PCC after 3 months and 6 months in a population with high vaccination coverage.

Marine creatures have an abundance of polysaccharides, active proteins, active peptides, and amino acids. With advancements in separation extraction and structure-activity relationship analysis technology, marine animal polysaccharides, as important components of marine animal active ingredients, are shown to exhibit a variety of biological activities such as immune regulation, hypoglycemic activities, antioxidant effects, lipid-lowering processes, and anticancer properties. This article examines the different types, biological activities, and applications of polysaccharides in biomedicine, aquaculture, food, cosmetics, and proposes potential research directions for pursuit by providing theoretical reference to promote the high-value and ecological development and utilization of marine animals.

Abstract Background Acute hypobaric hypoxia-induced brain injury has been a challenge in the health management of mountaineers; therefore, new neuroprotective agents are urgently required. Meldonium, a well-known cardioprotective drug, has been reported to have neuroprotective effects. However, the relevant mechanisms have not been elucidated. We hypothesized that meldonium may play a potentially novel role in hypobaric hypoxia cerebral injury. Methods We initially evaluated the neuroprotection efficacy of meldonium against acute hypoxia in mice and primary hippocampal neurons. The potential molecular targets of meldonium were screened using drug-target binding Huprot™ microarray chip and mass spectrometry analyses after which they were validated with surface plasmon resonance (SPR), molecular docking, and pull-down assay. The functional effects of such binding were explored through gene knockdown and overexpression. Results The study clearly shows that pretreatment with meldonium rapidly attenuates neuronal pathological damage, cerebral blood flow changes, and mitochondrial damage and its cascade response to oxidative stress injury, thereby improving survival rates in mice brain and primary hippocampal neurons, revealing the remarkable pharmacological efficacy of meldonium in acute high-altitude brain injury. On the one hand, we confirmed that meldonium directly interacts with phosphoglycerate kinase 1 (PGK1) to promote its activity, which improved glycolysis and pyruvate metabolism to promote ATP production. On the other hand, meldonium also ameliorates mitochondrial damage by PGK1 translocating to mitochondria under acute hypoxia to regulate the activity of TNF receptor-associated protein 1 (TRAP1) molecular chaperones. Conclusion These results further explain the mechanism of meldonium as an energy optimizer and provide a strategy for preventing acute hypobaric hypoxia brain injury at high altitudes.

Abstract To investigate the influence of spouses of business leaders on corporate decision-making behavior, we use data from 2003 to 2019 from Chinese listed family-controlled companies to examine the impact of entrepreneurs’ wives participating in corporate management on the risk-taking of family businesses. We found that entrepreneurs’ wives participating in company management significantly reduce the risk taking of family businesses, particularly when the wife is a shareholder in the company. Additionally, the wife’s age, level of education, and professional experience also affect her attitude and behavior toward participating in company management. When the wife is older and has a higher degree of education, the risk taking of the enterprise decreases. However, the wife’s rich professional experience can mitigate female conservatism and increase the company’s risk taking. Our research has implications for understanding gender differences in the context of the extension of marital power of Chinese entrepreneurs’ wives from the family to corporate decision-making and risk preferences. This helps to deepen our understanding of the role and status of women in China’s family business management.

Abstract Dark matter density can be significantly enhanced by the supermassive black hole at the galactic center, leading to a structure called dark matter spike. Dark matter spike may change the spacetime properties of black holes that constitute deviations from GR black holes. Based on these interesting background, we construct a set of solutions of black holes in a dark matter spike under the Newtonian approximation and full relativity. Combining the mass model of M87, we study the quasinormal modes of black holes in the scalar field and axial gravitational perturbation, then compared them with Schwarzschild black hole. Besides, the impacts of dark matter on the quasinormal mode of black holes have been studied in depth. In particular, in the axial gravitational perturbation, our results show that the impacts of dark matter spike on the quasinormal mode of black holes can reach up to $$10^{-4}$$ 10 - 4 . These new features from quasinormal mode of black holes under the Newtonian approximation and full relativity may provide some help for the establishment of the final dark matter model, and provide a new thought for the indirect detection of dark matter.

Abstract Background Cardiometabolic multimorbidity (CM) is emerging as a global health challenge. This study investigated the potential impact of muscle strength on the risk of CM in middle-aged and older Chinese adults. Methods In total, 7610 participants were identified from the China Health and Retirement Longitudinal Study (CHARLS). Muscle strength was measured by absolute, relative grip strength (normalized for body mass index) and chair-rising time which were classified into three categories according to tertiles stratified by gender. Cox proportional hazards models were adopted to evaluate the effect of muscle strength on CM. Results During follow-up, 235(3.76%) participants from none cardiometabolic diseases (CMD), 140 (19.23%) from diabetes, 119 (21.17%) from heart disease, and 22 (30.56%) from stroke progressed to CM. In participants who had low relative grip strength, CM was more likely to occur in individuals with heart disease at baseline (HR: 1.89, 95%CIs: 1.10 to 3.23). Those with high chair-rising time had a higher risk of CM than those with low chair-rising time in the individuals with diabetes (HR: 1.85, 95%CIs:1.20 to 2.86) and with heart disease (HR: 1.67, 95%CIs:1.04 to 2.70). However, we did not observe an association between muscle strength and CM in participants without CMD or with stroke at baseline. Conclusions In Chinese middle-aged and older adults, low relative grip strength was associated with a higher risk of CM in individuals with heart disease, while high chair-rising time was associated with a higher risk of CM in individuals with diabetes or heart disease.

Under the background of the “carbon peaking and carbon neutrality goals”, the salt cavern is an important place for geological storage and carbon sequestration. The limited knowledge of the quantity and quality of the salt cavern and immature investigation technology constrains the development and utilization of salt cavern. After analyzing the geological exploration reports on major salt mines, reserves reports, enterprise annual reports, and research articles, a scientific understanding and basic judgment of the amount and utilizability of salt caverns in China are obtained; a technical system of salt cavern resource survey is established through a test with comprehensive detection technology in the concentrated area of salt cavern. The results show that salt cavern resources in China are characterized by abundant reserves, wide distribution, feasible burial depth, and convenient utilization on large scale. The most abundant salt cavern resources occur in the east and central regions. The national salt cavern resources are divided into levels I, II, and III by using an availability evaluation method system of salt cavern resource. Level I accounting for about 29.4%, is mainly distributed in Jiangsu, Hubei, Henan, and other provinces in east and central China. Salt cavern resources in level I are preferred for development and utilization. Level II accounting for about 65.4%, is widely distributed in southwest, northwest, and centra China, and can be used as a prospective area for development and utilization. Salt cavern resources in level III accounting for about 5.2%, are not suitable for development and utilization. Ground geophysical exploration, which can identify the characteristics of the regional geology, salt layer geology, hydrogeology, and salt cavity distribution of the salt mining area, guides the site selection on the salt cavern construction; geophysical exploration of high precision, which can obtain the information of salt mine levels and cavity structure, benefit the construction and operation detection of storage. This study provides the basic data and technical support for the planning and development of salt cavern resources in China.

Snow melting and deicing of pavement has long been a subject that has attracted researchers from a diverse range of fields. In this paper, graphite modified asphalt concrete was used to melt snow and ice on pavement. The micromechanics theory of composites was used to establish the effective electrical conductivity model of graphite modified asphalt concrete. Flake graphite was used as the conductive phase. Considering the hexagonal inclusion of graphite particles, the Eshelby tensor was calculated. The modified self-consistent (MSC) model was based on the self-consistent theory and percolation theory considering the polygonal inclusion of Eshelby tensor. By comparison, the predicted values of the MSC model were in good agreement with the experimental values. The conductivity of graphite modified asphalt concrete was studied by the finite element (FE) simulation according to the prediction model. The predicted conductivity value of 0.13 S/m at 18Vol% of graphite volume fraction was applied to proceed the finite element analysis (FEA). The temperature field distribution and the ice-melting performance of graphite modified asphalt concrete were calculated by the influence of different input power, environment temperature and wind speed. Through analysis and research, the input power reaching between 600 W to 1000 W was more reasonable. Wind speed had a greater effect on ice melting time when the wind scale exceeded 3 scale at lower input power. The application of MSC model and FEA can play an important role in the design and application of deicing or snow melting systems.

Abstract Background Non-small cell lung cancer (NSCLC) patients with EGFR mutations exhibit an unfavorable response to immune checkpoint inhibitor (ICI) monotherapy, and their tumor microenvironment (TME) is usually immunosuppressed. TGF-β plays an important role in immunosuppression; however, the effects of TGF-β on the TME and the efficacy of anti-PD-1 immunotherapy against EGFR-mutated tumors remain unclear. Methods Corresponding in vitro studies used the TCGA database, clinical specimens, and self-constructed mouse cell lines with EGFR mutations. We utilized C57BL/6N and humanized M-NSG mouse models bearing EGFR-mutated NSCLC to investigate the effects of TGF-β on the TME and the combined efficacy of TGF-β blockade and anti-PD-1 therapy. The changes in immune cells were monitored by flow cytometry. The correlation between TGF-β and immunotherapy outcomes of EGFR-mutated NSCLC was verified by clinical samples. Results We identified that TGF-β was upregulated in EGFR-mutated NSCLC by EGFR activation and subsequent ERK1/2-p90RSK phosphorylation. TGF-β directly inhibited CD8+ T cell infiltration, proliferation, and cytotoxicity both in vitro and in vivo, but blocking TGF-β did not suppress the growth of EGFR-mutated tumors in vivo. Anti-TGF-β antibody combined with anti-PD-1 antibody significantly inhibited the proliferation of recombinant EGFR-mutated tumors in C57BL/6N mice, which was superior to their monotherapy. Mechanistically, the combination of anti-TGF-β and anti-PD-1 antibodies significantly increased the infiltration of CD8+ T cells and enhanced the anti-tumor function of CD8+ T cells. Moreover, we found that the expression of TGF-β1 in EGFR-TKI resistant cell lines was significantly higher than that in parental cell lines. The combination of anti-TGF-β and nivolumab significantly inhibited the proliferation of EGFR-TKI resistant tumors in humanized M-NSG mice and prolonged their survival. Conclusions Our results reveal that TGF-β expression is upregulated in NSCLC with EGFR mutations through the EGFR-ERK1/2-p90RSK signaling pathway. High TGF-β expression inhibits the infiltration and anti-tumor function of CD8+ T cells, contributing to the “cold” TME of EGFR-mutated tumors. Blocking TGF-β can reshape the TME and enhance the therapeutic efficacy of anti-PD-1 in EGFR-mutated tumors, which provides a potential combination immunotherapy strategy for advanced NSCLC patients with EGFR mutations. Graphical Abstract

Abstract Nuclear receptor coactivator 4 (NCOA4) has recently been recognized as a selective cargo receptor of ferritinophagy participating in ferroptosis. However, NCOA4 is also a coactivator that modulates the transcriptional activity of many vital nuclear receptors. Recent novel studies have documented the role of NCOA4 in healthy and pathogenic conditions via its modulation of iron- and non-iron-dependent metabolic pathways. NCOA4 exhibits non-ferritinophagic and iron-independent features such as promoting tumorigenesis and erythropoiesis, immunomodulation, regulating autophagy, and participating in DNA replication and mitosis. Full-length human-NCOA4 is composed of 614 amino acids, of which the N-terminal (1–237) contains nuclear-receptor-binding domains, while the C-terminal (238–614) principally contains a ferritin-binding domain. The exploration of the protein structure of NCOA4 suggests that NCOA4 possesses additional significant and complex functions based on its structural domains. Intriguingly, another three isoforms of NCOA4 that are produced by alternative splicing have been identified, which may also display disparate activities in physiological and pathological processes. Thus, NCOA4 has become an important bridge that encompasses interactions between immunity and metabolism. In this review, we outline the latest advances in the important regulating mechanisms underlying NCOA4 actions in health and disease conditions, providing insights into potential therapeutic interventions.

Polyacrylamide (PAM) in environmental water has become a major problem in water pollution management due to its high molecular mass, high viscosity and non-absorption by soil. CoFe2O4 with strong magnetic properties was prepared by solvent-thermal synthesis method and used as the catalyst for the removal on PAM in heterogeneous Electro-Fenton (EF) system. It showed that the removal efficiency of PAM by the heterogeneous EF system using CoFe2O4 catalyst was 92.01% at pH 3 after 120 min. Further studies indicated that ·OH was the most significant active species for the removal of PAM, and the contribution of ·O2− and SO4·− for the removal of PAM was less than 15%. The reusability test and XRD, XPS, FTIR analyses proved that the catalyst had good stability. After a repeated use for five times, the catalyst still had a high PAM removal rate and stable structure. The valence distribution and functional groups of the phase components of the catalyst did not change significantly before and after the reaction. The possible mechanism of catalyst activation of H2O2 was deduced by mechanism investigation. The CoFe2O4 is an efficient and promising catalyst for the removal of PAM wastewater. HIGHLIGHTS A Co–Fe bimetallic oxide catalyst was prepared by hydrothermal method and used to treat polymer-containing wastewater.; The prepared catalyst has strong magnetic properties, is easy to recover and can be reused (resource reuse).; In the CoFe2O4 heterogeneous system, the higher contaminant removal rate can be achieved with less catalyst dosage.;

We investigated the phenomenon of pseudo-Hopf bifurcation in a Filippov Hindmarsh-Rose neuronal system with threshold switching, and the existence of crossing limit cycles was proved by constructing the half-return mapping. Through the threshold control, the firing state of the system could be switched, allowing transitions from a non-periodic state to a periodic state, as well as the evolution from spiking to bursting. Furthermore, through threshold switching, the system exhibited the coexistence of multiple attractors, the system could be in multiple stable states, or have multiple stable sets that could attract system trajectories. This meant that neuronal system could exhibits diverse dynamical behaviors than being limited to a single stable state. The phenomenon of period-doubling bifurcation also indicated that the system will eventually enter a chaotic state. By extending the analysis to nonlinear neuronal systems, this study contributes to a deeper understanding of complex dynamics and provides valuable insights for designing state switching in the application of neural dynamics.

Abstract Background Time-restricted eating (TRE), a popular form of intermittent fasting, has shown benefits for improving metabolic diseases and cardiometabolic health. However, the effect of TRE in the regulation of blood pressure in primary hypertension remains unclear. Methods A 6-week randomized controlled trial was conducted, in which a total of 74 stage 1 primary hypertensive patients without high-risk were randomly assigned to Dietary Approaches to Stop Hypertension (DASH) group (n = 37) or DASH + TRE group (n = 37). Participants in the DASH + TRE group were instructed to consume their food within an 8-h window. Scientific research platform in We Chat application was used to track participants. The primary outcome was blood pressure. The secondary outcomes included body composition, cardiometabolic risk factors, inflammation-related parameters, urinary Na+ excretion, other clinical variables and safety outcomes. Results The reduction of systolic blood pressure and diastolic blood pressure were 5.595 ± 4.072 and 5.351 ± 5.643 mm Hg in the DASH group and 8.459 ± 4.260 and 9.459 ± 4.375 mm Hg in the DASH + TRE group. DASH + TRE group improved blood pressure diurnal rhythm. Subjects in DASH + TRE group had decreased extracellular water and increased urinary Na+ excretion. Furthermore, the decrease in blood pressure was associated with a reduction of extracellular water or increase in urinary Na+ excretion. In addition, safety outcomes such as nighttime hunger were also reported. Conclusion Our study demonstrated that 8-h TRE + DASH diet caused a greater decrease in blood pressure in stage 1 primary hypertensive patients than DASH diet. This study may provide novel insights into the benefits of lifestyle modification in the treatment of primary hypertension. Trial registration https://www.chictr.org.cn/ (ChiCTR2300069393, registered on March 15, 2023).

Abstract As the severity of global climate change escalates, carbon peak and carbon neutrality have emerged as international imperatives. Green taxation, a crucial fiscal strategy promoting the transition to a green low-carbon economy, demands thorough investigation regarding its efficacy and operational mechanisms. Predominantly, existing research has concentrated on the macroeconomic implications of green taxes, while their influence on regional green growth and innovation remains underexplored. This paper delineates green taxation in both a broad and narrow sense, elucidating its essence and potential in stimulating regional green progress and innovation. Utilizing panel data from 30 provinces in China spanning 2004 to 2021, a bidirectional fixed-effects model was developed for empirical analysis. Moreover, an impact mechanism model was constructed to delve into how green taxation specifically affects regional green development and innovation. Findings reveal that green taxation significantly fosters regional green growth and markedly enhances green innovation. Nonetheless, due to the resource crowding-out effect, it adversely impacts the comprehensive innovation capabilities of regional enterprises. This insight offers a fresh perspective on the paradoxical effects of green taxation, underscoring the necessity for a balanced approach in policy design and implementation. Drawing on these conclusions, the paper presents tailored policy recommendations.

Abstract When INS/GNSS (inertial navigation system/global navigation satellite system) integrated system is applied, it will be affected by the insufficient number of visible satellites, and even the satellite signal will be lost completely. At this time, the positioning error of INS accumulates with time, and the navigation accuracy decreases rapidly. Therefore, in order to improve the performance of INS/GNSS integration during the satellite signals interruption, a novel learning algorithm for neural network has been presented and used for intelligence integrated system in this article. First of all, determine the input and output of neural network for intelligent integrated system and a nonlinear model for weighs updating during neural network learning has been established. Then, the neural network learning based on strong tracking and square root UKF (unscented Kalman filter) is proposed for iterations of the nonlinear model. In this algorithm, the square root of the state covariance matrix is used to replace the covariance matrix in the classical UKF to avoid the filter divergence caused by the negative definite state covariance matrix. Meanwhile, the strong tracking coefficient is introduced to adjust the filter gain in real-time and improve the tracking capability to mutation state. Finally, an improved calculation method of strong tracking coefficient is presented to reduce the computational complexity in this algorithm. The results of the simulation test and the field-positioning data show that the proposed learning algorithm could improve the calculation stability and robustness of neural network. Therefore, the error accumulation of INS/GNSS integration is effectively compensated, and then the positioning accuracy of INS/GNSS intelligence integrated system has been improved.

Abstract Nucleic acid tests are essential for the accurate diagnosis and control of infectious diseases. However, current assays are not easily scalable for a large population, due to the requirement of laboratory settings or special equipment. Here, we developed an integrated box for instant nucleic acid screening which fully integrates nucleic acid release, amplification, and results visualization for self-service standalone test. Importantly, the operation of the box runs on a novel gamepad-like interface, which allows deployment of the box in home settings and operation by users without any prior professional training. The performance of the box is empowered by an RNA extraction-free sample inactivation process and nested recombinase polymerase amplification chemistry and exhibits sensitivity comparable to reverse transcription-quantitative polymerase chain reaction with high specificity for severe acute respiratory syndrome coronavirus 2 RNA in a reaction time of 30 minutes directly from fresh swab sample to results. These innovations make the box a novel platform for a convenient, accurate, and deployable point-of-care testing scheme.

ObjectiveTo determine the role of AAMP in osteosarcoma cells and explore the mechanism of invasion and metastasis of osteosarcoma cells regulated by AAMP through the YAP signaling pathway. MethodsPublic sequencing data analysis was used to explore the correlation between AAMP and osteosarcoma. q-PCR, Western blot, and immunohistochemistry were used to detect the expression levels of osteosarcoma cell-related molecules. CCK-8 was used to detect cell proliferation ability. Transwell and wound healing assays were used to detect the invasive and metastatic abilities of osteosarcoma cells. Immunofluorescence was used to detect the cell localization and expression levels of related molecules. ResultsHigh expression of AAMP was negatively correlated with the prognosis of patients with osteosarcoma (P

Abstract Background Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host–parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases. Methods Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host–parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice. Results This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice. Conclusions Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals. Graphical Abstract

Abstract Introduction College students’ physical fitness is likely to be directly related to their cells’ health. However, there is a lack of literature on whether the relationship between cell health and college students’ physical fitness is direct or indirect. This study used a structural equation modeling (SEM) approach to investigate the connection between cell health and college students’ physical fitness. Methods This cross-sectional study collected data from 838 volunteers (502 males and 336 females, average age of 18.74 ± 1.5 years) who were college students from the Shandong province of China in July 2023. Initially, we obtained anthropometric measurements and conducted physical fitness tests on the students. Then, we performed Pearson correlation analysis and principal component analysis to screen variables and explore potentially influencing factors. Finally, we examined associations between the variables and determined whether there were direct or indirect influences among factors using SEM. Results The results revealed a significant correlation between the cell health factor and the muscle strength factor (path coefficient = 0.97; p

Abstract Three-dimensional (3D) glass chips are promising waveguide platforms for building hybrid 3D photonic circuits due to their 3D topological capabilities, large transparent windows, and low coupling dispersion. At present, the key challenge in scaling down a benchtop optical system to a glass chip is the lack of precise methods for controlling the mode field and optical coupling of 3D waveguide circuits. Here, we propose an overlap-controlled multi-scan (OCMS) method based on laser-direct lithography that allows customizing the refractive index profile of 3D waveguides with high spatial precision in a variety of glasses. On the basis of this method, we achieve variable mode-field distribution, robust and broadband coupling, and thereby demonstrate dispersionless LP21-mode conversion of supercontinuum pulses with the largest deviation of

Abstract We study an evaporating black hole in the boundary conformal field theory (BCFT) model under the fully time-dependent AdS-Vaidya spacetime geometry. We introduce the time-dependent finite bath termed the effective Hawking radiation region. This is described by a nontrivial BCFT solution that acts as a time-dependent brane which we call the moving end-of-the-radiation (METR) brane that leads to a new type of Hubeny-Rangamani-Takayanagi surface. We further examine the island formulation in this particular time-dependent spacetime. The Page curve is calculated by using Holographic Entanglement Entropy (HEE) in the context of double holography.

Abstract Background Understanding factors associated with antiretroviral treatment (ART) adherence is crucial for ART success among people living with HIV (PLHIV) in the “test and treat” era. Multiple psychosocial factors tend to coexist and have a syndemic effect on ART adherence. We aimed to explore factors associated with ART adherence and the syndemic effect of multiple psychosocial factors on ART adherence among PLHIV newly starting ART in Guangdong Province, China. Methods Newly diagnosed PLHIV from six cities in Guangdong Province were recruited between May 2018 and June 2019, and then followed up from May 2019 to August 2020. Baseline and follow-up data were collected from a questionnaire and the national HIV surveillance system, the follow-up data of which were analyzed in this study. A Center for Adherence Support Evaluation (CASE) index > 10 points was defined as optimal ART adherence, which was measured via participants’ self-reported adherence during follow-up survey. Multivariable logistic regression was used to identify factors associated with ART adherence. Exploratory factor analysis (EFA) and multi-order latent variable structural equation modeling (SEM) were performed to explore the syndemic effect of multiple psychosocial factors on ART adherence. Results A total of 734 (68.53%) follow-up participants were finally included in this study among the 1071 baseline participants, of whom 91.28% (670/734) had self-reported optimal ART adherence. Unemployment (aOR = 1.75, 95%CI: 1.01–3.02), no medication reminder (aOR = 2.28, 95%CI: 1.09–4.74), low medication self-efficacy (aOR = 2.28, 95%CI: 1.27–4.10), low social cohesion (aOR = 1.82, 95%CI: 1.03–3.19), no social participation (aOR = 5.65, 95%CI: 1.71–18.63), and ART side effects (aOR = 0.46, 95%CI: 0.26–0.81) were barriers to optimal ART adherence. The EFA and second-order latent variable SEM showed a linear relationship (standardized coefficient = 0.43, P

Abstract Catalytic films work well in degradation of organic matters. However, catalytic activity and stability of films are challenging factors. A nanoscale zero-valent iron (NZVI) incorporated porous PAN fiber (Fe-PAN) film was thus developed through a one-step cryogenic auxiliary electrospinning method. The Fe-PAN film overcame the problem in the traditional multistep preparation process. The excellent intrinsic properties of the polymer in the film were maintained. It exhibited high catalytic activity (> 95% conversion in just 4 min) and excellent stability and reusability, due to the synergistic interaction between PAN and NZVI. The degradation process was optimized by the Box-Behnken design, leading to the optimal condition: pH = 2.8, temperature = 56 °C, and oxidant concentration = 4.2 mmol/L. The degradation followed the 2nd order kinetic equation and was due to the reactions by ·OH and O2 -· radicals. This study demonstrates the great potentials of the Fe-PAN film for industrial applications.

Abstract Background Investigating the trend of changes in the occurrence of necrotizing enterocolitis (NEC) in preterm infants during 9 years and analyzing the risk factors of NEC with the purpose of providing reference for clinical diagnosis and treatment of NEC. Methods Clinical data of NEC in preterm infants with Bell’s stage ≥ II from January 2013 to December 2021 in the Neonatology Department of the Third Affiliated Hospital of Zunyi Medical University was retrospectively analyzed. Trends in the occurrence of NEC in preterm infants were analyzed by the trend chi-square test. Subsequently, the general data (sex, gestational age, singleton or multiple births, birth weight, serum albumin, alkaline phosphatase, sepsis, blood transfusion, mechanical ventilation, RDS, arterial catheterization) and perinatal data (intrauterine distress, turbid amniotic fluid, premature rupture of membranes, mode of delivery, fetal heart abnormalities, diabetes mellitus) were collected; then, the risk factors for NEC were analyzed by univariate and multivariate logistic-regression analysis. Results In the past 9 years, 77 cases of NEC occurred, with the incidence rate of 1.95%, and the incidence of NEC in preterm infants has been increasing year by year (P

Abstract The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

Abstract Background Neuroblastoma (NB) patients with amplified MYCN often face a grim prognosis and are resistant to existing therapies, yet MYCN protein is considered undruggable. KAP1 (also named TRIM28) plays a crucial role in multiple biological activities. This study aimed to investigate the relationship between KAP1 and MYCN in NB. Methods Transcriptome analyses and luciferase reporter assay identified that KAP1 was a downstream target of MYCN. The effects of KAP1 on cancer cell proliferation and colony formation were explored using the loss-of-function assays in vitro and in vivo. RNA stability detection was used to examine the influence of KAP1 on MYCN expression. The mechanisms of KAP1 to maintain MYCN mRNA stabilization were mainly investigated by mass spectrum, immunoprecipitation, RIP-qPCR, and western blotting. In addition, a xenograft mouse model was used to reveal the antitumor effect of STM2457 on NB. Results Here we identified KAP1 as a critical regulator of MYCN mRNA stability by protecting the RNA N6-methyladenosine (m6A) reader YTHDC1 protein degradation. KAP1 was highly expressed in clinical MYCN-amplified NB and was upregulated by MYCN. Reciprocally, KAP1 knockdown reduced MYCN mRNA stability and inhibited MYCN-amplified NB progression. Mechanistically, KAP1 regulated the stability of MYCN mRNA in an m6A-dependent manner. KAP1 formed a complex with YTHDC1 and RNA m6A writer METTL3 to regulate m6A-modified MYCN mRNA stability. KAP1 depletion decreased YTHDC1 protein stability and promoted MYCN mRNA degradation. Inhibiting MYCN mRNA m6A modification synergized with chemotherapy to restrain tumor progression in MYCN-amplified NB. Conclusions Our research demonstrates that KAP1, transcriptionally activated by MYCN, forms a complex with YTHDC1 and METTL3, which in turn maintain the stabilization of MYCN mRNA in an m6A-dependent manner. Targeting m6A modification by STM2457, a small-molecule inhibitor of METTL3, could downregulate MYCN expression and attenuate tumor proliferation. This finding provides a new alternative putative therapeutic strategy for MYCN-amplified NB.

Abstract Background Porcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal Health. The current detection methods of Cysticercus cellulosae cannot meet the needs of large-scale and rapid detection in the field. We hypothesized that the immunofluorescence chromatography test strip (ICS) for detecting Cysticercus cellulosae, according to optimization of a series of reaction systems was conducted, and sensitivity, specificity, and stability testing, and was finally compared with ELISA. This method utilizes Eu3+-labeled time-resolved fluorescent microspheres (TRFM) coupled with TSOL18 antigen to detect TSOL18 antibodies in infected pig sera. Results ICS and autopsy have highly consistent diagnostic results (n = 133), as determined by Cohen’s κ analysis (κ = 0.925). And the results showed that the proposed ICS are high sensitivity (0.9459) with specificity (0.9792). The ICS was unable to detect positive samples of other parasites. It can be stored for at least six months at 4℃. Conclusions In summary, we established a TRFM-ICS method with higher sensitivity and specificity than indirect ELISA. Results obtained from serum samples can be read within 10 min, indicating a rapid, user-friendly test suitable for large-scale field detection.

Abstract Background This study aimed to examine the reporting quality of existing economic evaluations for negotiated glucose-lowering drugs (GLDs) included in China National Reimbursement Drug List (NRDL) using the Consolidated Health Economic Evaluation Reporting Standards 2013 (CHEERS 2013). Methods We performed a systematic literature research through 7 databases to identify published economic evaluations for GLDs included in the China NRDL up to March 2021. Reporting quality of identified studies was assessed by two independent reviewers based on the CHEERS checklist. The Kruskal–Wallis test and Mann–Whitney U test were performed to examine the association between reporting quality and characteristics of the identified studies. Results We have identified 24 studies, which evaluated six GLDs types. The average score rate of the included studies was 77.41% (SD:13.23%, Range 47.62%-91.67%). Among all the required reporting items, characterizing heterogeneity (score rate = 4.17%) was the least satisfied item. Among six parts of CHEERS, results part scored least at 0.55 (score rate = 54.79%) because of the incompleteness of characterizing uncertainty. Results from the Kruskal–Wallis test and Mann–Whitney U test showed that model choice, journal type, type of economic evaluations, and study perspective were associated with the reporting quality of the studies. Conclusions There remains room to improve the reporting quality of economic evaluations for GLDs in NRDL. Checklists such as CHEERS should be widely used to improve the reporting quality of economic researches in China.

316L stainless steel (SS) is widely applied as microimplant anchorage (MIA) due to its excellent mechanical properties. However, the risk that the oral microorganisms can corrode 316L SS is fully neglected. Microbiologically influenced corrosion (MIC) of 316L SS is essential to the health and safety of all patients because the accelerated corrosion caused by the oral microbiota can trigger the release of Cr and Ni ions. This study investigated the corrosion behavior and mechanism of subgingival microbiota on 316L SS by 16S rRNA and metagenome sequencing, electrochemical measurements, and surface characterization techniques. Multispecies biofilms were formed by the oral subgingival microbiota in the simulated oral anaerobic environment on 316L SS surfaces, significantly accelerating the corrosion in the form of pitting. The microbiota samples collected from the subjects differed in biofilm compositions, corrosion behaviors, and mechanisms. The oral subgingival microbiota contributed to the accelerated corrosion of 316L SS via acidic metabolites and extracellular electron transfer. Our findings provide a new insight into the underlying mechanisms of oral microbial corrosion and guide the design of oral microbial corrosion-resistant materials.

Determining gallic acid in honey can provide information for assessing the nutritional value and tracing the source of honey. However, the complex matrix of honey and the low content of gallic acid may hamper the detection. Therefore, it is important to select an appropriate sample preparation method. This work established an air-assisted dispersive micro-solid phase extraction combined with a high-performance liquid chromatography method to determine gallic acid in honey. Zinc/nickel/aluminium layered double hydroxides were selected as the adsorbent to extract gallic acids in diluted honey samples. Under air-assisted extraction, the adsorbents adsorbed gallic acid in honey via anion exchange. Subsequently, the isolated adsorbents were dissolved in a 1% phosphoric acid solution. A high-performance liquid chromatography-UV-Vis detector was used for gallic acid detection. Under the optimised conditions, gallic acid showed good linearity over the concentration range of 0.005-10.0 mg.L-1 with a coefficient of determination greater than 0.999. The detection limit and quantification limit were 13.5 and 45 ng.g-1, respectively. The recoveries were 89.8-93.4%, with the intra-day and inter-day relative standard deviations in the range of 0.71-1.17% and 0.76-1.27%, respectively. The method possesses the advantages of simplicity, rapidity, economy and environmental friendliness and is suitable for detecting gallic acid in honey.

Supercapacitors (SCs) are considered promising energy storge systems because of their outstanding power density, fast charge and discharge rate and long-term cycling stability. The exploitation of cheap and efficient electrode materials is the key to improve the performance of supercapacitors. As the battery-type materials, transition metal phosphides (TMPs) possess high theoretical specific capacity, good electrical conductivity and superior structural stability, which have been extensively studied to be electrode materials for supercapacitors. In this review, we summarize the up-to-date progress on TMPs materials from diversified synthetic methods, diverse nanostructures and several prominent TMPs and their composites in application of supercapacitors. In the end, we also propose the remaining challenges toward the rational discovery and synthesis of high-performance TMP electrodes materials for energy storage.

Abstract Flash Joule heating (FJH) is an emerging and profitable technology for converting inexhaustible biomass into flash graphene (FG). However, it is challenging to produce biomass FG continuously due to the lack of an integrated device. Furthermore, the high-carbon footprint induced by both excessive energy allocation for massive pyrolytic volatiles release and carbon black utilization in alternating current-FJH (AC-FJH) reaction exacerbates this challenge. Here, we create an integrated automatic system with energy requirement-oriented allocation to achieve continuous biomass FG production with a much lower carbon footprint. The programmable logic controller flexibly coordinated the FJH modular components to realize the turnover of biomass FG production. Furthermore, we propose pyrolysis-FJH nexus to achieve biomass FG production. Initially, we utilize pyrolysis to release biomass pyrolytic volatiles, and subsequently carry out the FJH reaction to focus on optimizing the FG structure. Importantly, biochar with appropriate resistance is self-sufficient to initiate the FJH reaction. Accordingly, the medium-temperature biochar-based FG production without carbon black utilization exhibited low carbon emission (1.9 g CO2-eq g−1 graphene), equivalent to a reduction of up to ~86.1% compared to biomass-based FG production. Undoubtedly, this integrated automatic system assisted by pyrolysis-FJH nexus can facilitate biomass FG into a broad spectrum of applications.

Abstract To handle the disturbances and uncertainties issue in the control of the stabilized platform toolface angle, a composite control approach based on a backstepping sliding mode control (BSMC) method with a nonlinear disturbance observer (NDO) is proposed. First, a nonlinear mathematical model of the stabilized platform is established, and the NDO is employed to observe and compensate for the external disturbance. Then, the BSMC control approach based on the nonlinear mathematical model is designed to improve the robustness of the stabilized platform control system. The asymptotic stability of the designed controller and NDO convergence are mathematically verified using the Lyapunov theory. Furthermore, to address the dead zone torque caused by mechanical friction on the stabilized platform, which could lead to instability in the toolface angle, a novel dead zone torque estimation algorithm is presented. Finally, in comparison with other advanced control methods, simulation results show the superiority and robustness of the proposed scheme under complex disturbances from the downhole environment. And drilling simulation experiment results are provided to validate the robustness and adaptivity of the proposed method.

Abstract Interpolation of probability distributions can be formulated as an optimal transport problem. Positive matrix, which can be viewed as the generalization of probability distribution to higher dimension, is used in quantum theory to describe the state of a quantum system. Here, a quantum‐inspired method for the interpolation of positive matrices is proposed. Particularly, this method employs the quantum state purification of the positive matrices in an extended space. Since pure state controllability can be easily achieved using open‐loop coherent control, the continuous interpolation of positive matrices is given as a completely positive map induced by simulating the optimal control for pure state transfer. The quantum‐inspired interpolation is shape‐preserving with applications to tensor field processing.