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Abstract Background Genetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population. Methods A case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders. Results Our study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes. Conclusion This study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes. Trial registration www.chictr.org.cn ID: ChiCTR2300071579 2023-05-18.

Abstract Background Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins. Methods The keywords “lipid droplets” and “metabolic diseases” were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like “lipid droplets”, “lipid droplet-associated proteins”, “fatty liver disease”, “diabetes”, “diabetic kidney disease”, “obesity”, “atherosclerosis”, “hyperlipidemia”, “natural drug monomers” and “natural compounds”, the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized. Results The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases. Conclusion Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications. Graphical Abstract

ABSTRACTNitrogen mainly exists as nitrate in aqueous environments. In karst areas, nitrate pollution caused by anthropogenic activities severely endangers aqueous systems. In order to identify nitrate sources, nitrate in the cave water of Mahuang Cave was comprehensively analysed using hydrochemistry, δ15N-δ18O isotopes and stable isotope analysis in R. The results indicate that the nitrate content in the cave water presented insignificant seasonal variations but significant spatial variations. Compared with the variation of δ15N-NO3−, the seasonal variation of δ18O-NO3− was positive (2.68‰) in the dry season and negative (−0.52‰) in the wet season. The variation of NO3− and Cl− and the isotopes of NO3− (δ15N, δ18O) suggest multiple sources of NO3− in the water. The average contribution of different nitrate sources in the karst cave water was assessed by the SIAR model: chemical fertilisers (46.29%) > soil nitrogen (30.57%) > manure & sewage (14.14%) > atmospheric precipitation (9.14%) in the dry season and chemical fertilisers (61.86%) > soil nitrogen (20.29%) > manure & sewage (12.43%) > atmospheric precipitation(5.57%) in the wet season. The contribution in dry and wet seasons was dominated by chemical fertilisers and soil nitrogen.

Abstract Background Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality. Methods Herein we present 12 genetic variants identified in seven clinically well-characterized Chinese patients with CPS1 deficiency who were admitted to the Children’s Medical Center of Peking University First Hospital from September 2014 to August 2023. Results Seven patients (two male and five female patients including two sisters) experienced symptoms onset between 2 days and 13 years of age, and they were diagnosed with CPS1 deficiency between 2 months and 20 years. Peak blood ammonia levels ranged from 160 to 1,000 µmol/L. Three patients showed early-onset CPS1 deficiency, with only one surviving after treatment with sodium phenylbutyrate, N-carbamoyl-L-glutamate, and liver transplantation at 4 months, showing a favorable outcome. The remaining four patients had late-onset CPS1 deficiency, presenting with mental retardation, psychiatric symptoms, and self-selected low-protein diets. Among the 12 CPS1 variants identified in these patients, 10 were novel, with all patients exhibiting compound heterozygosity for CPS1 mutant alleles. Seven variants (c.149T > C, c.616 A > T, c.1145 C > T, c.1294G > A, c.3029 C > T, c.3503 A > T, and c.3793 C > T) resulted in single amino acid substitutions. Three frameshift variations (c.2493del, c.3067dup, and c.3241del) were identified, leading to enzyme truncation. One mutation (c.3506_3508del) caused an in-frame single amino acid deletion, while another (c.2895 + 2T > C) resulted in aberrant splicing. Conclusions Except for two known variants, all other variants were identified as novel. No hotspot variants were observed among the patients. Our data contribute to expanding the mutation spectrum of CPS1.

Abstract Background Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. Methods We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. Results We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. Conclusions We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

Abstract Investigating proton transport at the interface in an excited state facilitates the mechanistic investigation and utilization of nanomaterials. However, there is a lack of suitable tools for in-situ and interfacial analysis. Here we addresses this gap by in-situ observing the proton transport of graphene quantum dots (GQDs) in an excited state through reduction of magnetic resonance relaxation time. Experimental results, utilizing 0.1 mT ultra-low-field nuclear magnetic resonance relaxometry compatible with a light source, reveal the light-induced proton dissociation and acidity of GQDs’ microenvironment in the excited state (Hammett acidity function: –13.40). Theoretical calculations demonstrate significant acidity enhancement in –OH functionalized GQDs with light induction ( $${{\mathrm{p}}}{K}_{{\text{a}}}^{*}$$ p K a * = –4.62, stronger than that of H2SO4). Simulations highlight the contributions of edge and phenolic –OH groups to proton dissociation. The light-induced superacidic microenvironment of GQDs benefits functionalization and improves the catalytic performances of GQDs. Importantly, this work advances the understanding of interfacial properties of light-induced sp 2–sp 3 carbon nanostructure and provides a valuable tool for exploring catalyst interfaces in photocatalysis.

Background: Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. Methods: To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. Results: In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. Conclusion: Collectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this article: This study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.

Abstract Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells that represent the interface between blood cells on one side and hepatocytes on the other side. LSECs not only form a barrier within the hepatic sinus, but also play important physiological functions such as regulating hepatic vascular pressure, anti-inflammatory and anti-fibrotic. Pathologically, pathogenic factors can induce LSECs capillarization, that is, loss of fenestra and dysfunction, which are conducive to early steatosis, lay the foundation for the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), and accelerate metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. The unique localization, phenotype, and function of LSECs make them potential candidates for reducing liver injury, inflammation, and preventing or reversing fibrosis in the future.

Abstract Background and aims To investigate the clinical features, ALDH5A1 gene variations, treatment, and prognosis of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency. Materials and methods This retrospective study evaluated the findings in 13 Chinese patients with SSADH deficiency admitted to the Pediatric Department of Peking University First Hospital from September 2013 to September 2023. Results Thirteen patients (seven male and six female patients; two sibling sisters) had the symptoms aged from 1 month to 1 year. Their urine 4-hydroxybutyrate acid levels were elevated and were accompanied by mildly increased serum lactate levels. Brain magnetic resonance imaging (MRI) showed symmetric abnormal signals in both sides of the globus pallidus and other areas. All 13 patients had psychomotor retardation, with seven showing epileptic seizures. Among the 18 variants of the ALDH5A1 gene identified in these 13 patients, six were previously reported, while 12 were novel variants. Among the 12 novel variants, three (c.85_116del, c.206_222dup, c.762C > G) were pathogenic variants; five (c.427delA, c.515G > A, c.637C > T, c.755G > T, c.1274T > C) were likely pathogenic; and the remaining four (c.454G > C, c.479C > T, c.1480G > A, c.1501G > C) were variants of uncertain significance. The patients received drugs such as L-carnitine, vigabatrin, and taurine, along with symptomatic treatment. Their urine 4-hydroxybutyric acid levels showed variable degrees of reduction. Conclusions A cohort of 13 cases with early-onset SSADH deficiency was analyzed. Onset of symptoms occurred from 1 month to 1 year of age. Twelve novel variants of the ALDH5A1 gene were identified.

Abstract Background Although research has explored the association between atherogenic index of plasma (AIP) and prediabetes and diabetes, there is still not sufficient available evidence the role of physical activity (PA) in this relationship. Our purpose is to examine the complex connections between AIP, PA, and prediabetes and diabetes in a young and middle‐aged population. Methods This study included 2220 individuals from the general population, aged 20–60 years. AIP was calculated from the logarithm of the triglyceride (TG) to high‐density lipoprotein cholesterol (HDL‐C) ratio. PA was assessed depending to the American Heart Association (AHA) criteria and categorized into medium‐high and low PA levels. We used binary logistic regression to explore associations and subsequently performed sensitivity and subgroup analyses. Results The 2220 participants had a mean age of 38 years, with a mean AIP of −0.1185, and a prediabetes and diabetes prevalence of 7.2%. After adjusting for auxiliary variables, AIP was positively correlated with prediabetes and diabetes (odds ratio [OR]: 3.447, 95% confidence interval [CI]: 1.829–6.497). In the low PA population, the prevalence of prediabetes and diabetes raised significantly with higher AIP (OR: 3.678, 95% CI: 1.819–7.434). This association was not meaningful in the medium to high PA population (OR: 1.925, 95% CI: 0.411–9.007). Joint and sensitivity analyze results also showed agreement. Restricted cubic spline identified a linear relationship between AIP and the prevalence of prediabetes and diabetes. Notably, the prevalence significantly increases when AIP values exceed −0.16 (p for linearity

IntroductionClassical Muscovy duck reovirus (C-MDRV) and goose-origin Muscovy duck reovirus (Go-MDRV) infections cause “Liver white-spots disease” in Muscovy duckling and gosling. It is difficult to differentiate the infections caused by C-MDRV and Go-MDRV using conventional serological methods.MethodsSpecific primers were designed and synthesized according to σNS and λA nucleotide sequences of C-MDRV and Go-MDRV, respectively. The PCR amplified products were cloned into the pMD-18-T vector. The recombinant plasmid DNA was used to establish an SYBR Green І based duplex real-time PCR assay for the simultaneous detection and differentiation of C-MDRV and Go-MDRV using high-resolution melting (HRM) analysis. The specificity, sensitivity, and repeatability of the methodology were examined based on the optimization of the reaction system and amplification conditions.ResultsC-MDRV and Go-MDRV were identified by their distinctive melting temperatures with 84.50 ± 0.25°C for C-MDRV and 87.50 ± 0.20°C for Go-MDRV, respectively. The amplifications were specific, and other non-targeted waterfowl viruses employed in this study did not show normalized melting peaks. The intra- and inter-assay coefficients of variations were between 0.05 and 1.83%, demonstrating good repeatability. The detection limits of this assay were 51.4 copies·μl−1 for C-MDRV and 61.8 copies·μl−1 for Go-MDRV, respectively. A total of 45 clinical samples were tested by RT-qPCR, with positive rates of 15.56% for C-MDRV and 22.22% for Go-MDRV, without co-infections.DiscussionThese results suggest that this duplex RT-qPCR method is highly sensitive, specific, and reproducible. The HRM assay established in this study provides a powerful tool for the differential detection and epidemiological investigation of C-MDRV and Go-MDRV.

RationaleKidney inflammation plays a crucial role in the pathogenesis of IgA nephropathy (IgAN), yet the specific phenotypes of immune cells involved in disease progression remain incompletely understood. Utilizing joint profiling through longitudinal single-cell RNA-sequencing (scRNAseq) and single-cell assay for transposase-accessible chromatin sequencing (scATACseq) can provide a comprehensive framework for elucidating the development of cell subset diversity and how chromatin accessibility regulates transcription.ObjectiveWe aimed to characterize the dynamic immune cellular landscape at a high resolution in an early IgAN mouse model with acute kidney injury (AKI).Methods and resultsA murine model was utilized to mimic 3 immunological states –”immune stability (IS), immune activation (IA) and immune remission (IR)” in early human IgAN-associated glomerulopathy during AKI, achieved through lipopolysaccharide (LPS) injection. Urinary albumin to creatinine ratio (UACR) was measured to further validate the exacerbation and resolution of kidney inflammation during this course. Paired scRNAseq and scATACseq analysis was performed on CD45+ immune cells isolated from kidney tissues obtained from CTRL (healthy vehicle), IS, IA and IR (4 or 5 mice each). The analyses revealed 7 major cell types and 24 clusters based on 72304 single-cell transcriptomes, allowing for the identification and characterization of various immune cell types within each cluster. Our data offer an impartial depiction of the immunological characteristics, as the proportions of immune cell types fluctuated throughout different stages of the disease. Specifically, these analyses also revealed novel subpopulations, such as a macrophage subset (Nlrp1b Mac) with distinct epigenetic features and a unique transcription factor motif profile, potentially exerting immunoregulatory effects, as well as an early subset of Tex distinguished by their effector and cytolytic potential (CX3CR1-transTeff). Furthermore, in order to investigate the potential interaction between immune cells and renal resident cells, we conducted single-cell RNA sequencing on kidney cells obtained from a separate cohort of IS and IA mice without isolating immune cells. These findings underscored the diverse roles played by macrophages and CD8+ T cells in maintaining homeostasis of endothelial cells (ECs) under stress.ConclusionsThis study presents a comprehensive analysis of the dynamic changes in immune cell profiles in a model of IgAN, identifying key cell types and their roles and interactions. These findings significantly contribute to the understanding of the pathogenesis of IgAN and may provide potential targets for therapeutic intervention.

Summary: The manipulation and mechanism of two-dimensional (2D) transition metal dichalcogenides (TMDs) by external electric field are significant to the photoelectric properties. Herein, the 2D MoS2 nanosheets were oxidized to form MoS2-MoO3 local heterojunctions by an electric field, applied in multistable memristors for the proposal of NanoQR code. A modified thermal oxidation model was derived to reveal the mechanism of local electric oxidation on 2D MoS2. From current-voltage curves, the barrier height of the MoS2 device showed an increase of 0.39 eV due to local oxidation after applying voltage for 480 s. Based on density-functional theory, the increase of barrier height was calculated as 0.38 eV between MoS2-MoS2 and MoS2-MoO3 supercells. The 2D MoS2-MoO3 local heterojunctions were further applied as multistable memory storage at the nanoscale. The findings suggest a novel strategy for controlling local electric oxidation on 2D TMDs to manipulate the properties for the application of photoelectric memory nanodevices.

Abstract Background Wolbachia-infected thelytokous Trichogramma wasps have been considered as potential effective biocontrol agents against lepidopteran pests in agriculture and forests. However, intra-specific competition may arise when Wolbachia-infected thelytokous Trichogramma coexist with their uninfected bisexual counterparts in fields or during mass-rearing procedures. This competition could potentially impact the efficacy of Trichogramma females in biological control programs. Results This study examined the parasitic capacities of bisexual (TdB) and Wolbachia-infected thelytokous (TdT) strains of Trichogramma dendrolimi as influenced by host density (ranging from 5 to 70 host eggs) and wasp density (two, four, and six females per arena). The experiments involved inter-strain competition between TdB and TdT strains (Inter-Td) as well as intra-strain competition within the TdT (Intra-TdT) or TdB (Intra-TdB) strains. Results revealed that females in the Inter-Td group exhibited a higher attack rate compared to those in the Intra-TdT and Intra-TdB groups, irrespective of wasp density. Specifically, when six females were present, the Inter-Td group showed significantly shorter host handling times than the Intra-TdT group. Within intra-strain cohorts, TdT females displayed a lower attack rate than TdB females when four or six females were present, and longer host handling times when six females were present. Mutual interference between individuals was not affected by competition types. Females of the Inter-Td group exhibited a higher probability of superparasitism than those of the Intra-TdB group or Inter-Td group. When both strains coexisted, the proportion of TdT offspring with six females was higher than that with two females or four females. Male ratios of bisexual offspring in Inter-Td groups were higher than those in Intra-TdB groups. The male ratio of bisexual offspring in the Inter-Td group increased with wasp density. Conclusions Our study highlights the negative impact of Wolbachia on parasitic capacity of Trichogramma females, increasing the likelihood of superparasitism. The coexistence of both strains enhances total parasitic efficacy, albeit resulting in a higher proportion of male offspring compared to scenarios with only uninfected females. The results will provide the reference for the usage of Wolbachia-infected thelytokous strain of T. dendrolimi in augmentative biological control programs.

Abstract Background Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported. Results Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR. Conclusions Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.

Abstract Background Metarhizium rileyi is an important entomopathogenic fungus which has a wide range of host pests. In this work, the virulence of M. rileyi EFNL-08 against 3rd instar larvae of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), was quantified. Additionally, the infection process and aspects of the host immunological response were described in the laboratory. Results Bioassay results proved that M. rileyi was highly virulent to 3rd instar S. frugiperda larvae with 98.33% mortality at 1 × 108 conidia/ml. Scanning electron microscopy was used to monitor morphological aspects of the infection process. When hyphal bodies (Hbs) of M. rileyi were injected into the hemocoel of host, they were not recognized by the host’s immune system as invaders. There were nonsignificant differences in the hemocytes and phenoloxidase activity between the infected and control larvae at the initial 30 h, indicating that fungus successfully avoids the attack from the immune system. However, it inhibited the enzyme activity at the latest stage when Hbs reached a high density. After infection with M. rileyi, the activity of glutathione-S-transferase (GST) of S. frugiperda larvae presented a significant upward trend, while the activity of acetylcholinesterase (AchE) initially increased, followed by a decrease, and eventually stabilized. However, the activity of both detoxification enzymes in the control group showed slight fluctuations in the initial stage, and then stabilized at a low level. Conclusion Obtained results provided new insights into the virulence and potential physiological responses of M. rileyi. This provides ideas for further development of novel and efficient entomopathogenic fungi (EPF) for pest control.

Abstract Background The protozoan parasite Toxoplasma gondii encodes dozens of phosphatases, among which a plant-like phosphatase absent from mammalian genomes named PPKL, which is involved in regulating brassinosteroid signaling in Arabidopsis, was identified in the genome. Among the Apicomplexa parasites, T. gondii is an important and representative pathogen in humans and animals. PPKL was previously identified to modulate the apical integrity and morphology of the ookinetes and parasite motility and transmission in another important parasite, Plasmodium falciparum. However, the exact function of PPKL in the asexual stages of T. gondii remains unknown. Methods The plant auxin-inducible degron (AID) system was applied to dissect the phenotypes of PPKL in T. gondii. We first analyzed the phenotypes of the AID parasites at an induction time of 24 h, by staining of different organelles using their corresponding markers. These analyses were further conducted for the parasites grown in auxin for 6 and 12 h using a quantitative approach and for the type II strain ME49 of AID parasites. To further understand the phenotypes, the potential protein interactions were analyzed using a proximity biotin labeling approach. The essential role of PPKL in parasite replication was revealed. Results PPKL is localized in the apical region and nucleus and partially distributed in the cytoplasm of the parasite. The phenotyping of PPKL showed its essentiality for parasite replication and morphology. Further dissections demonstrate that PPKL is required for the maturation of daughter parasites in the mother cells, resulting in multiple nuclei in a single parasite. The phenotype of the daughter parasites and parasite morphology were observed in another type of T. gondii strain ME49. The substantial defect in parasite replication and morphology could be rescued by genetic complementation, thus supporting its essential function for PPKL in the formation of parasites. The protein interaction analysis showed the potential interaction of PPKL with diverse proteins, thus explaining the importance of PPKL in the parasite. Conclusions PPKL plays an important role in the formation of daughter parasites, revealing its subtle involvement in the proper maturation of the daughter parasites during division. Our detailed analysis also demonstrated that depletion of PPKL resulted in elongated tubulin fibers in the parasites. The important roles in the parasites are potentially attributed to the protein interaction mediated by kelch domains on the protein. Taken together, these findings contribute to our understanding of a key phosphatase involved in parasite replication, suggesting the potential of this phosphatase as a pharmaceutic target. Graphical Abstract

Turtle shell dorsal armor comprises a typical lightweight laminated composite structural material, which is constructed by cuticle and bone layer, with high specific strength and high fracture toughness. The red-eared slider turtle, a widely studied species of turtle, has a rich hierarchical structure. In this paper, according to the structure of red-eared slider turtle shell dorsal armor and the characteristics of each layer as well as by taking into full consideration of the fine structure of cuticle and ventral cortex of the shell dorsal armor, two bionic foam silicone rubber sandwich structures of different levels were prepared. Low-velocity impact test and finite element simulation analysis were carried out to study the mechanical response, specific absorbed energy, and damage mode of the two bionic sandwich structures under different impact energies, hammerhead shapes, and hammerhead radii. By comparing the mechanical response and specific energy absorption with the existing ordinary sandwich structure, we find that the two sandwich structures modeled in this paper exhibit better impact resistance than the ordinary sandwich structure. The shape and radius of the hammer head have a significant effect on the energy absorption characteristics of the sandwich structure, and the damage mode under the hemispherical hammer head is mainly dominated by tensile tearing damage, while the damage mode of extrusion fracture is more obvious under the impact of the conical hammer head. With the increase of the radius of the hammer head, the absorbed energy and specific energy absorption of the sandwich structure increases.

Carbon-based quantum dots (CQDs) have been shown to have promising application value in tumor diagnosis. Their use, however, is severely hindered by the complicated nature of the nanostructures in the CQDs. Furthermore, it seems impossible to formulate the mechanisms involved using the inadequate theoretical frameworks that are currently available for CQDs. In this review, we re-consider the structure-property relationships of CQDs and summarize the current state of development of CQDs-based tumor diagnosis based on biological theories that are fully developed. The advantages and deficiencies of recent research on CQDs-based tumor diagnosis are thus explained in terms of the manifestation of nine essential changes in cell physiology. This review makes significant progress in addressing related problems encountered with other nanomaterials.

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is currently difficult to treat, even when therapies are combined with immune checkpoint blockade (ICB). A novel strategy for immunotherapy would be to maximize the therapeutic potential of oncolytic viruses (OVs), which have been proven to engage the regulation of tumor microenvironment (TME) and cause-specific T-cell responses. To boost tumor sensitivity to ICB therapy, this study aimed to investigate how glutathione peroxide 4 (GPX4)-loaded OVs affect CD8+ T cells and repair the immunosuppressive environment. Here, we successfully constructed a novel recombinant oncolytic vaccinia virus (OVV) encoding the mouse GPX4 gene. We found the OVV-GPX4 effectively replicated in tumor cells and prompted the expression of GPX4 in T cells. Our research indicated that OVV-GPX4 could reshape the TME, rectify the depletion of CD8+T cells, and enhance the antitumor effects of ICB therapy.

IntroductionGeranylgeranyltransferase Subunit Beta (RABGGTB) was expressed at higher levels in patients with Amyotrophic lateral sclerosis (ALS) compared with healthy controls. This study aims to observe the expression of RABGGTB in different cells from patients with ALS and different diseases.MethodsIn this case–control study, we collected peripheral blood from patients with ALS and healthy controls, and compared the expression of RABGGTB in natural killer cells (NK), T cells and B cells between patients with ALS and healthy controls by flow cytometry. And compared the expression of RABGGTB in monocytes and monocyte-derived macrophages from patients with ALS, Parkinson’s disease (PD), acute cerebrovascular disease (ACVD), and healthy controls by flow cytometry and immunofluorescence. Then flow cytometry was used to detect the expression of RABGGTB in monocytes from SOD1G93A mice and WT mice.ResultsThe expression of RABGGTB was not significantly changed in NK cells, cytotoxic T cells (CTL), helper T cells (Th), regulatory T cells (Treg), and B cells from patients with ALS compared to healthy controls. And the expression of RABGGTB in monocytes and monocyte-derived macrophages was higher in the ALS group than in the PD, ACVD and control group. The expression of RABGGTB was significantly higher in monocytes of SOD1G93A mice compared to WT mice.ConclusionThese findings suggest that RABGGTB expression was increased in monocytes and monocyte-derived macrophages from patients with ALS, not in NK, CTL, Th, Treg, and B cells. Future studies are needed to find the clinical implication of RABGGTB in ALS.

Background and purposeThis study explores the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and mortality among Parkinson’s disease (PD) patients, providing evidence for the potential benefits of vitamin D (VD) supplementation.MethodsPD patients were collected from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2020. These patients were categorized based on their serum 25(OH)D levels: deficiency, insufficiency, and sufficiency. We compared demographic information and analyzed mortality data from the National Death Index. A restricted cubic spline model assessed the nonlinear association between 25(OH)D levels and mortality, complemented by multivariable Cox regression analysis. Consistency of results was checked through subgroup analysis.ResultsThe study included 364 PD patients: 87 (23.9%) with VD deficiency, 121 (33.2%) with insufficiency, and 156 (42.9%) with sufficiency. Demographically, 46.4% were male, and 56% were over 65 years. The deficiency group predominantly consisted of Mexican Americans (53.1%), had lower income levels, a higher unmarried rate, and increased liver disease incidence. The analysis showed a U-shaped curve between 25(OH)D levels and mortality risk, with the lowest risk at 78.68 nmol/L (p-non-linear = 0.007, p-overall = 0.008). Kaplan–Meier analysis found the highest survival rates in patients with 25(OH)D levels between 75–100 nmol/L (p = 0.039). Compared to this group, patients with levels below 50 nmol/L had a 3.52-fold increased mortality risk (95% CI = 1.58–7.86, p = 0.002), and those above 100 nmol/L had a 2.92-fold increase (95% CI = 1.06–8.05, p = 0.038). Age-specific subgroup analysis (p = 0.009) revealed that both very low (100 nmol/L) levels increased mortality risk in patients under 65, while levels below 75 nmol/L raised mortality risk in older patients.ConclusionSerum 25(OH)D levels are nonlinearly linked to mortality in PD patients, with optimal survival rates occurring at 75–100 nmol/L. Deviations from this range increase the risk of death.

To further enhance the recovery rate of low temperature waste heat, the low temperature flue gas in the sinter annular cooler is chosen as the heat source of organic Rankine cycle (ORC) system in the current study, and the system thermal-economic performance evaluation are conducted. The thermal-economic performance models of ORC system are established firstly, and the butane and isopentane are selected to constitute the mixed working fluid. Then the changes of system performance with the mass fraction of isopentane (MR601a) and ORC crucial parameters are evaluated comprehensively, and the bi-objective optimization is applied to ascertain the optimal ORC crucial parameters under various MR601a. The results indicate that the MR601a of 0.6 can obtain the maximum glide temperature. The higher the evaporating temperature is, and the lower the condensing temperature is, the larger the exergy efficiency is, while the smaller the levelized energy cost is. There is an optimal superheat degree to make the ORC system achieve the better overall performance under various MR601a. The exergy efficiency of butane is the maximum with a respectable waste heat recovery rate of 64.18 %, while the levelized energy cost of isopentane in the whole conditions is the minimum with the better economic performance.

Ulcerative colitis (UC) is a recurring inflammatory bowel disease, in which oxidative stress plays a role in its progression, and regulation of the oxidative/antioxidative balance has been suggested as a potential target for the treatment of UC. The aim of this study was to evaluate the protective effect of andrographolide against UC and its potential antioxidant properties by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Dextran sulfate sodium (DSS) -induced UC mice and the LPS-induced HT29 inflammatory cell model were established to uncover the potential mechanisms of andrographolide. ML385, a Nrf2 inhibitor, was used in both models to assess whether andrographolide exerts a protective effect against UC through the Nrf2/HO-1 pathway. The in vivo experiment showed that andrographolide ameliorated the symptoms and histopathology of DSS-induced mice and restored the expressions of ZO-1, Occludin-1 and Claudin-1. Meanwhile, DSS-induced oxidative stress and inflammation were suppressed by andrographolide treatment, along with the upregulation of key proteins in the Nrf2/HO-1 pathway. In vitro experiments showed that andrographolide attenuated LPS-induced excessive generation of ROS in HT29 cells, reduced inflammatory factors, and upregulated the expression of proteins related to tight junctions and Nrf2/HO-1 pathway. In addition, ML385 abolished the beneficial effect of andrographolide. In conclusion, the protective effect of andrographolide against UC may involve the suppression of oxidative stress and inflammation via the Nrf2/HO-1 pathway.

Although the store-operated Ca2+ entry (SOCE) plays a critical role in maintaining Ca2+ homeostasis in vascular endothelial cells (VECs), its role in regulating endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation is largely unknown. Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are the most common gastrointestinal disorders with no effective cures. The present study applied N,N,N′,N′-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) as a Ca2+ chelator in the endoplasmic reticulum (ER) to study the SOCE/EDH-mediated vasorelaxation of micro-arteries and their involvements in the pathogenesis of IBD and IBS. Human submucosal arterioles and the second-order branch of 6–8 weeks male C57BL/6 mouse mesenteric arterioles were used, and TPEN-induced vasorelaxation was recorded by Danish DMT520A microvascular measuring system. The mice were fed water with 2.5 % dextran sulfate sodium for 7 days to induce mouse model of ulcerative colitis, and water avoidance stress was used to induce mouse model of IBS. The statistical significance of differences in the means of experimental groups was determined using a t-test for two groups or one-way ANOVA for more than two groups. TPEN concentration-dependently induced vasorelaxation of human colonic submucosal arterioles and the second-order branch of murine mesenteric arteries in endothelium-dependent manner. TPEN-induced vasorelaxation was much greater in the arteries pre-constricted by noradrenaline than those by high K+. While TPEN-induced vasorelaxation was unaffected by inhibitors of NO and PGI2, it was significantly inhibited by the selective inhibitors of IKCa and SKCa channels but was potentiated by their activator. Moreover, TPEN-induced vasorelaxation was attenuated by selective inhibitors of NCX, NKA, SOCE, STIM translocation and Orai transportation. Finally, TPEN-induced vasorelaxation via SOCE/EDH was impaired in colitic mice but remained intact in IBS mice. Interestingly, TPEN could rescue vagus neurotransmitter ACh-induced vasorelaxation that was impaired in IBS mice. Therefore, since TPEN-induced SOCE/EDH-mediated vasorelaxation of mesenteric arteries is well-preserved to be able to rescue ACh-induced vasorelaxation impaired in IBS, TPEN has therapeutic potentials for IBS.

This paper studies the synchronization and tracking issue for the connected and automated vehicle (CAV) platoon with mixed-order nonlinear vehicle dynamics. Previous researches have demonstrated that vehicle platoons can improve traffic efficiency and minimize the incidence of traffic collisions. However, vehicles within the same platoon may have different-order dynamics in practical scenarios. The heterogeneity issue of a vehicle platoon caused by the different-order dynamics is difficult to address by existing platoon control methods. Therefore, the platoon synchronization and tracking control problem for the heterogeneous CAV platoon which consists of mixed-order vehicles with a hybrid of second- and third-order dynamics is formulated in this paper. The proposed novel distributed sliding mode (DSM) control protocols for vehicles with second- and third-order dynamics aim to guarantee the convergence of vehicle state errors and the stability of the heterogeneous platoon. The distributed neural network-based adaptive estimation technique are developed in this paper to approximate the unknown uncertainties and compensate for the model nonlinearities of the platoon system. The uniform ultimate boundedness of errors and string stability are substantiated through the Lyapunov theory and infinity-norm technique. The efficacy of the developed platoon control strategies can be verified by the numerical examples.

Abstract Retinoid-related orphan receptor gamma t (RORγt) is the lineage-specific transcription factor for T helper 17 (Th17) cells. Our previous study demonstrated that STAT3 likely participates in the activation of RORCE2 (a novel enhancer of the RORγt gene) in Th17 cells. However, the detailed mechanism is still unclear. Here, we demonstrate that both STAT3 and SOX-5 mediate the enhancer activity of RORCE2 in vitro. Deletion of the STAT3 binding site (STAT3-BS) in RORCE2 impaired RORγt expression and Th17 differentiation, resulting in reduced severity of experimental autoimmune encephalomyelitis (EAE). Mechanistically, STAT3 and SOX-5 bind the RORCE2 region and recruit the chromatin remodeling factor BRG1 to remodel the nucleosomes positioned at this region. Collectively, our data suggest that STAT3 and SOX-5 mediate the differentiation of Th17 cells through the induction of BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells.

Abstract The Asian corn borer, Ostrinia furnacalis (Guenée) (Lepidoptera: Crambidae), is one of the most harmful pests of maize in Asia. It poses a significant threat to maize production, causing economic losses due to its strong ecological adaptation. In this study, we compared and analyzed the hemolymph proteome between freezing and resistance-freezing O. furnacalis strains using two-dimensional gel electrophoresis to gain insights into the mechanisms of cold resistance. The results revealed that 300–400 hemolymph protein spots were common, with 24 spots showing differences between the two strains. Spectrometry analysis revealed 21 protein spots, including 17 upregulated spots and 4 downregulated ones. The expression of upregulation/downregulation proteins plays a crucial role in the metabolism, energy supply, and defense reaction of insects. Proteomics research not only provides a method for investigating protein expression patterns but also identifies numerous attractive candidates for further exploration.

The mechanism of fine grains migration is the basis and key to understand the seepage erosion process of gravel soil, which is significance to study the disaster-caused mesomechanism of rain erosion process on sandy gravel slopes. However, the migration mode and critical condition for the transition of migration state are unclear. The migration types of fine grains differ from different physical and hydraulic conditions. To reveal the overall movement characteristics of fine grains and the critical conditions for the change of their motion state during the process of gravel soil erosion, this study adopted the visual cylindrical infiltration test and discrete element numerical simulation to analyze the influencing factors and mechanism of the fine grains migration, deposition, and self-dredging. The results show that: 1) the migration of fine grains is significantly affected by the gradation and hydraulic gradient but not by the initial porosity. The gradation has a greater effect than the hydraulic gradient. 2) The overall motion of fine grains under hydraulic forces can be divided into two states: deposition and self-dredging. The fine grains of gravel soil with unstable internal structure are in the self-dredging state, and that with stable and transitional internal structure will change from deposition to self-dredging with the increase of hydraulic gradient. 3) The motion state of fine grains has an obvious boundary under the combined effects of grain size ratio and hydraulic gradient, and the critical condition for fine grains transition from deposition to self-dredging is obtained to be \begin{document}$ i = 3.4 - 0.12{{\text{e}}^{\left( {{D_{15}}/{d_{85}}} \right)/1.5}} $\end{document}.

Abstract Engineering piezo/ferroelectricity in two-dimensional materials holds significant implications for advancing the manufacture of state-of-the-art multifunctional materials. The inborn nonstoichiometric propensity of two-dimensional transition metal dichalcogenides provides a spiffy ready-available solution for breaking inversion centrosymmetry, thereby conducing to circumvent size effect challenges in conventional perovskite oxide ferroelectrics. Here, we show the extendable and ubiquitous piezo/ferroelectricity within nonstoichiometric two-dimensional transition metal dichalcogenides that are predominantly centrosymmetric during standard stoichiometric cases. The emerged piezo/ferroelectric traits are aroused from the sliding of van der Waals layers and displacement of interlayer metal atoms triggered by the Frankel defects of heterogeneous interlayer native metal atom intercalation. We demonstrate two-dimensional chromium selenides nanogenerator and iron tellurides ferroelectric multilevel memristors as two representative applications. This innovative approach to engineering piezo/ferroelectricity in ultrathin transition metal dichalcogenides may provide a potential avenue to consolidate piezo/ferroelectricity with featured two-dimensional materials to fabricate multifunctional materials and distinguished multiferroic.

Abstract Backgroud Multiple studies have identified pathogenic germline variants in cancer susceptibility genes (CSGs) in Chinese lung cancer patients; however, accurate assessment of these variants' contributions to cancer predisposition is always hampered by the absence of data on the prevalence of these variants in the general population. It is necessary to conduct a large‐scale case–control study to identify CSGs that significantly increase the risk of lung cancer. Materials and methods We performed targeted sequencing of a CSGs panel in 1117 lung cancer patients and 16,327 controls from the general Chinese population. Results In comparison to controls, lung cancer patients had a considerably higher prevalence of pathogenic and likely pathogenic (P/LP) variations. Among lung cancer patients, 72% of P/LP variants carriers did not have a family cancer history, who would be ignored if germline testing was only provided for patients meeting family history‐based criteria. Furthermore, compared to individuals with late‐onset lung cancer, patients with early‐onset lung cancer had a considerably higher prevalence of P/LP variations. With odds ratios (ORs) ranging from 4‐fold (BRCA1: OR, 4.193; 95%CI, 1.382–10.768) to 29‐fold (TP53: OR, 29.281; 95%CI, 1.523–1705.506), P/LP variants in the BRCA1 and TP53 genes were discovered to be strongly related to increased lung cancer risk. Additionally, with ORs ranging from 7.322‐fold to infinity, we discovered 23 variations previously categorized as non‐P/LP variants were highly enriched in lung cancer patients. Conclusion Our findings indicated that P/LP variants in BRCA1 and TP53 conferred increased risk of lung cancer in Chinese.

Abstract Cross‐affiliation emerges as a new and fast‐developing means to promote collaboration in financial research. We find that the average number of affiliations reported per author in the top‐three finance journals increases steadily from 1.1 to 1.3 from 1995 to 2016. Scale‐free power laws characterize the resulting highly‐skewed distributions of top finance journal publications of worldwide institutions. We propose an explanation of the scale‐invariance, based on a network model featuring nonlinear growth and linear preferential attachment. The model indicates that success‐breeds‐success engenders 87% of total publications and hence the dispersion in research output, while accelerated growth of collaboration reduces the heterogeneity.

Abstract The attacker in white-box model has full access to software implementation of a cryptographic algorithm and full control over its execution environment. In order to solve the issues of high storage cost and inadequate security about most current white-box cryptographic schemes, WAS, an improved white-box cryptographic algorithm over AS iteration is proposed. This scheme utilizes the AS iterative structure to construct a lookup table with a five-layer ASASA structure, and the maximum distance separable matrix is used as a linear layer to achieve complete diffusion in a small number of rounds. Attackers can be prevented from recovering the key under black-box model. The length of nonlinear layer S and affine layer A in lookup table is 16 bits, which effectively avoids decomposition attack against the ASASA structure and makes the algorithm possess anti-key extraction security under the white-box model, while WAS possesses weak white-box (32 KB, 112)-space hardness to satisfy anti-code lifting security. WAS has provable security and better storage cost than existing schemes, with the same anti-key extraction security and anti-code lifting security, only 128 KB of memory space is required in WAS, which is only 14% of SPACE-16 algorithm and 33% of Yoroi-16 algorithm.

Background: Whether the effect of the unfixed mesh during laparoscopic total extraperitoneal (TEP) inguinal hernia repair can lead to hernia recurrence remains controversial. Methods: The PubMed, Cochrane Library, and EMBASE databases were searched to retrieve clinical randomized controlled trials (RCTs) comparing nonfixation of mesh and fixation of mesh in TEP inguinal hernia repair, and we performed a metaanalysis with RevMan 5.3 software. Results: Fifteen RCTs were included in the metaanalysis, which showed that the operation time (P = 0.001) of the unfixed mesh group was shorter than that of the fixed mesh group; additionally, the postoperative 24-h pain score (P = 0.04) and incidence of urinary retention (P = 0.001) were lower in the unfixed mesh group. There was no significant difference between the unfixed mesh group and the fixed mesh group in terms of hospital stay (P = 0.47), time to resume normal activities (P = 0.51), incidence of haematoma (P = 0.96), incidence of chronic pain (P = 0.20), and recurrence rate (P = 0.09). Conclusion: Unfixed mesh in TEP inguinal hernia repair shows no elevated recurrence rates compared to fixed mesh and is clinically safe.

Underground telecommunication cables are highly susceptible to damage from excavation activities. Preventing accidental damage to underground telecommunication cables is critical and necessary. In this study, we present field trial results of monitoring excavation activities near underground fiber cables using an intensity-based phase-sensitive optical time-domain reflectometer (φ-OTDR). The reasons for choosing intensity-based φ-OTDR for excavation monitoring are presented and analyzed. The vibration signals generated by four typical individual excavation events, i.e., cutting, hammering, digging, and tamping at five different field trial sites, as well as five different mixed events in the fifth field trial site were investigated. The findings indicate that various types of events can generate vibration signals with different features. Typically, fundamental peak frequencies of cutting, hammering and tamping events ranged from 30 to 40 Hz, 11 to 15 Hz, and 30 to 40 Hz, respectively. Digging events, on the other hand, presented a broadband frequency spectrum without a distinct peak frequency. Moreover, due to differences in environmental conditions, even identical excavation events conducted with the same machine may also generate vibration signals with different characteristics. The diverse field trial results presented offer valuable insights for both research and the practical implementation of excavation monitoring techniques for underground cables.

Raman spectroscopy with the advantages of the in situ and simultaneous detection of multi-components has been widely used in the identification and quantitative detection of gas. As a type of scattering spectroscopy, the detection sensitivity of Raman spectroscopy is relatively lower, mainly due to the low signal collection efficiency. This paper presents the design and assembly of a multi-channel cavity-enhanced Raman spectroscopy system, optimizing the structure of the sample pool to reduce the loss of the laser and increase the excitation intensity of the Raman signals. Moreover, three channels are used to collect Raman signals to increase the signal collection efficiency for improving the detection sensitivity. The results showed that the limits of detection for the CH4, H2, CO2, O2, and N2 gases were calculated to be 3.1, 34.9, 17.9, 27, and 35.2 ppm, respectively. The established calibration curves showed that the correlation coefficients were all greater than 0.999, indicating an excellent linear correlation and high level of reliability. Meanwhile, under long-time integration detection, the Raman signals of CH4, H2, and CO2 could be clearly distinguished at the concentrations of 10, 10, and 50 ppm, respectively. The results indicated that the designed Raman system possesses broad application prospects in complex field environments.

Satellite communication links are vulnerable to attacks due to the lack of necessary security protection and can be considered as a white-box environment. In a white-box environment, cryptanalysts can access the intermediate processes of the algorithm and even manipulate or change the operating environment. Cryptanalysts can obtain keys or tamper with important data in many ways, which makes data communication unsecured. To solve the problem, a lightweight white-box cipher over Addition/Rotation/XOR (ARX) structure (LWARX) is proposed, which has 48 rounds of iterations through an unbalanced Feistel structure. On this basis, some of its linear operations are represented as lookup tables, and a secure external coding method is combined to complete the white-box implementation. The design and white-box implementation of the algorithm has resulted in a lighter and more rational structure, and still provides sufficient obfuscation of the data even when the S-box is discarded. The test results show that the average encryption speed is 37.53 Kbps, and average encryption speed after white-box implementation is 30.05 Kbps. And it can resist various attacks. The security of the algorithm against common attack methods such as differential analysis, linear analysis, code lifting attacks and BGE attacks is given in the paper with security analysis and specific values. This scheme balances computing efficiency and security, takes up little space, can be applied to scenarios with limited hardware and software resources, and broadens the application area of white-box cryptography.

The magnesium salt Mg(NO3)2·2H2O from laterite nickel ore nitric acid leaching process can be reused by thermal decomposition using calciner. To improve the performance of the calciner, a new numerical model integrating the gas-particle hydrodynamics and the particle pyrolysis reaction was established by Euler-Lagrange approach. In particular, the particle size variation caused by pyrolysis reaction was considered to accurately describe the gas-particle hydrodynamics. The particle pyrolysis model was developed to realize the interphase mass transfer. The P-1 model was modified to realize interphase radiation heat transfer. Then, the influence of different parameters on the thermal decomposition processes was discussed by using the established model. Finally, the optimal conditions for Mg(NO3)2·2H2O thermal decomposition were determined via response surface optimization analysis. The results show that the thermal decomposition of Mg(NO3)2·2H2O can be improved by increasing the initial hot gas temperature, reaction zone height, and decreasing treatment capacity of Mg(NO3)2·2H2O. The degree of influence of each parameter on thermal decomposition follows the order of initial hot gas temperature > treatment capacity of Mg(NO3)2·2H2O > reaction zone height. The decomposition rate of 99.99 % is obtained at optimized conditions of initial hot gas temperature 1111 K, Mg(NO3)2·2H2O treatment capacity 251 kg/h and reaction zone height 9 m.

Avian coccidiosis, caused by Eimeria parasites, continues to devastate the poultry industry and results in significant economic losses. Ionophore coccidiostats, such as maduramycin and monensin, are widely used for prophylaxis of coccidiosis in poultry. Nevertheless, their efficacy has been challenged by widespread drug resistance. However, the underlying mechanisms have not been revealed. Understanding the targets and resistance mechanisms to anticoccidials is critical to combat this major parasitic disease. In the present study, maduramycin-resistant (MRR) and drug-sensitive (DS) sporozoites of Eimeria tenella were purified for transcriptomic and metabolomic analysis. The transcriptome analysis revealed 5016 differentially expressed genes (DEGs) in MRR compared to DS, and KEGG pathway enrichment analysis indicated that DEGs were involved in spliceosome, carbon metabolism, glycolysis, and biosynthesis of amino acids. In the untargeted metabolomics assay, 297 differentially expressed metabolites (DEMs) were identified in MRR compared to DS, and KEGG pathway enrichment analysis indicated that these DEMs were involved in 10 pathways, including fructose and mannose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, and glutathione metabolism. Targeted metabolomic analysis revealed 14 DEMs in MRR compared to DS, and KEGG pathway analysis indicated that these DEMs were involved in 20 pathways, including fructose and mannose metabolism, glycolysis/gluconeogenesis, and carbon metabolism. Compared to DS, energy homeostasis and amino acid metabolism were differentially regulated in MRR. Our results provide gene and metabolite expression landscapes of E. tenella following maduramycin induction. This study is the first work involving integrated transcriptomic and metabolomic analyses to identify the key pathways to understand the molecular and metabolic mechanisms underlying drug resistance to polyether ionophores in coccidia.

The apicoplast is a four-membrane plastid found in the apicomplexans, which harbors biosynthesis and organelle housekeeping activities in the matrix. However, the mechanism driving the flux of metabolites, in and out, remains unknown. Here, we used TurboID and genome engineering to identify apicoplast transporters in Toxoplasma gondii. Among the many novel transporters, we show that one pair of apicomplexan monocarboxylate transporters (AMTs) appears to have evolved from a putative host cell that engulfed a red alga. Protein depletion showed that AMT1 and AMT2 are critical for parasite growth. Metabolite analyses supported the notion that AMT1 and AMT2 are associated with biosynthesis of isoprenoids and fatty acids. However, stronger phenotypic defects were observed for AMT2, including in the inability to establish T. gondii parasite virulence in mice. This study clarifies, significantly, the mystery of apicoplast transporter composition and reveals the importance of the pair of AMTs in maintaining the apicoplast activity in apicomplexans.

Depression is a major global health issue that urgently requires innovative and precise treatment options. In this context, saikosaponin has emerged as a promising candidate, offering a variety of therapeutic benefits that may be effective in combating depression. This review delves into the multifaceted potential of saikosaponins in alleviating depressive symptoms. We summarized the effects of saikosaponins on structural and functional neuroplasticity, elaborated the regulatory mechanism of saikosaponins in modulating key factors that affect neuroplasticity, such as inflammation, the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, and the brain-gut axis. Moreover, this paper highlights existing gaps in current researches and outlines directions for future studies. A detailed plan is provided for the future clinical application of saikosaponins, advocating for more targeted researches to speed up its transition from preclinical trials to clinical practice.

Abstract Background Although chronic inflammation, oxidative stress, airway remodeling, and protease-antiprotease imbalance have been implicated in chronic obstructive pulmonary disease (COPD), the exact pathogenesis is still obscure. Gene transcription and post-transcriptional regulation have been taken into account as key regulators of COPD occurrence and development. Identifying the hub genes and constructing biological regulatory networks at the post-transcriptional level will help extend current knowledge on COPD pathogenesis and develop potential drugs. Methods All lung tissues from non-smokers (n = 6), smokers without COPD (smokers, n = 7), and smokers with COPD (COPD, n = 7) were collected to detect messenger RNA (mRNA), microRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) expression and identify the hub genes. Biological regulatory networks were constructed at the post-transcriptional level, including the RNA-binding protein (RBP)-hub gene interaction network and the competitive endogenous RNA (ceRNA) network. In addition, we assessed the composition and abundance of immune cells in COPD lung tissue and predicted potential therapeutic drugs for COPD. Finally, the hub genes were confirmed at both the RNA and protein levels. Results Among the 20 participants, a total of 121169 mRNA transcripts, 1871 miRNA transcripts, 4244 circRNA transcripts, and 122130 lncRNA transcripts were detected. There were differences in the expression of 1561 mRNAs, 48 miRNAs, 33 circRNAs, and 545 lncRNAs between smokers and non-smokers, as well as 1289 mRNAs, 69 miRNAs, 32 circRNAs, and 433 lncRNAs between smokers and COPD patients. 18 hub genes were identified in COPD. TGF-β signaling and Wnt/β-catenin signaling may be involved in the development of COPD. Furthermore, the circRNA/lncRNA-miRNA-mRNA ceRNA networks and the RBP-hub gene interaction network were also constructed. Analysis of the immune cell infiltration level revealed that M2 macrophages and activated NK cells were increased in COPD lung tissues. Finally, we identified that the ITK inhibitor and oxybutynin chloride may be effective in treating COPD. Conclusions We identified several novel hub genes involved in COPD pathogenesis. TGF-β signaling and Wnt/β-catenin signaling were the most dysregulated pathways in COPD patients. Our study constructed post-transcriptional biological regulatory networks and predicted small-molecule drugs for the treatment of COPD, which enhanced the existing understanding of COPD pathogenesis and suggested an innovative direction for the therapeutic intervention of the disease.

The migration and transformation of dissolved organic matter (DOM) in highly heterogeneous and permeable karst aquifers are of great significance to the regional carbon cycle but are rarely explored, especially in response to extreme climate events. In this study, we utilized spectroscopic indices to investigate variations in DOM concentration, composition, and origin in Mahuang Cave, Southwest China, from August 2020 to October 2022. The findings indicate that meteorological conditions, hydrological pathways, and in–situ metabolism primarily control DOM dynamics in karst cave drip water. However, due to the complex cave fractures and stratigraphy, the DOM composition at the four monitoring sites—classified into slow and fast seepage—showed different responses to meteorological events. Therefore, surface reworking must be fully considered when assessing the environmental information recorded by cave sediments.

Postbiotics possess various functional activities, closely linked to their source bacterial strains and preparation methods. Therefore, the functional activities of postbiotics need to be evaluated through in vitro and in vivo methods. This study aims to prepare a postbiotic and explore its antihemolytic, anti-inflammatory, antioxidant, and antibacterial activities. Specifically, a postbiotic preparation named PostbioP-6 was prepared by intercepting 1–5 kDa of Lacticaseibacillus paracasei Postbiotic-P6 fermentation broth. The results demonstrate that PostbioP-6 exhibited notable biological activities across multiple assays. It showed significant antihemolytic activity, with a 4.9–48.1% inhibition rate at 10–50% concentrations. Anti-inflammatory effects were observed both in vitro, where 8–40% PostbioP-6 was comparable to 259.1–645.4 μg/mL diclofenac sodium, and in vivo, where 3.5 and 4.0 μL/mL PostbioP-6 significantly reduced neutrophil counts in inflamed zebrafish (p < 0.05). Antioxidant properties were evident through increased reducing power (OD700 increased from 0.279 to 2.322 at 1.25–12.5% concentrations), DPPH radical scavenging activity (38.9–92.4% scavenging rate at 2.5–50% concentrations), and hydroxyl radical scavenging activity (4.66–10.38% scavenging rate at 0.5–4% concentrations). Additionally, PostbioP-6 demonstrated antimicrobial activity against two Gram-positive bacteria, eight Gram-negative bacteria, and one fungus. Furthermore, PostbioP-6 significantly inhibited the increase in peroxide value and malondialdehyde content in cookies, highlighting its potential application in food preservation. In conclusion, we prepared a novel postbiotic, termed PostbioP-6, which proved to have prominent anti-hemolytic, anti-inflammatory, antioxidant, and broad-spectrum antimicrobial activities. The multifunctional properties of PostbioP-6 position it as a potentially effective functional food supplement or preservative. In the future, further research is necessary to elucidate the precise mechanisms of action, identify the active components, and validate its biological activities in animal models or clinical trials.

Pleurotus citrinopileatus Singer (PCS) has attracted increasing attention as a raw material for medicine and food. Its quality is greatly affected by the accumulation of metabolites, which varies with the applied drying methods. In this study, we utilize an approach based on ultra-high-performance liquid chromatography/Q Exactive mass spectrometry (UHPLC-QE-MS) to reveal the metabolic profiles of PCS from three different drying methods (natural air-drying, NAD; hot-air-drying, HAD; vacuum freeze-drying, VFD). The results showed that lipids, amino acids and their derivatives were all important secondary metabolites produced during NAD, HAD and VFD treatments, with the key differential metabolites of PCS during drying including fifteen lipids and seven amino acids. Meanwhile, VFD was the best way for long-term preservation of dried PCS. Hot-drying methods, especially HAD, can improve the medicinal component of PCS. Furthermore, KEGG enrichment analysis highlighted 16 pathways and indicated that amino acid metabolism might be the key metabolite pathway for the PCS drying process. Our study elucidates the relationship between drying methods and metabolites or metabolic pathways of PCS to determine the mechanisms affecting the quality of PCS, and finally provides reference values for further development and application in functional food and medications.

The bioaccessibility of particle-bound hydrophobic organic contaminants, such as polycyclic aromatic hydrocarbons (PAHs), and the factors influencing their re-release are crucial for assessing potential human health risks via inhalation and hand-mouth exposure. However, the mechanisms by which various factors affect the re-release of PAHs in body fluids, particularly in response to environmental changes like freeze-thaw cycles, remain unclear. To obtain a better understanding, an in vitro method was employed to investigate the re-release processes of PAHs from different soil types (ferrallitic soil and calcareous soil) in simulated body fluids (simulated lung fluid and simulated saliva) under varying freeze-thaw conditions (0, 15, and 30 cycles). The findings indicated that the bioaccessibilities of phenanthrene and pyrene decreased with the frequency of freeze-thaw cycles, which were constrained by soil nature and simulated body fluids compositions as well. Additionally, this study observed that the portion of reversible adsorption of PAHs declined after exposure to freeze-thaw cycles in a nonlinear manner, suggesting that the potential human health risk associated with PAHs could be mitigated due to the “aging effect” which occurred as PAHs became less bioaccessible over time. These results underscore the importance of considering the characteristics of pollutants, body fluids, and environmental media when conducting a precise assessment of the human health risks posed by such contaminants.

In order to improve the efficiency of the implementation of the authenticated encryption algorithm without compromising the security of the algorithm, a new authenticated encryption algorithm AEUR was designed.Firstly, based on the uBlock round function, with resistance to internal collision attacks as the security objective, a mixed integer linear programming approach was used to search for generic iterative component R(t,s) to meet the security objective.Secondly, the authenticated encryption algorithm AEUR was designed by using this component.AEUR consisted of two parts: authenticated encryption and decrypted verification, both of which performed the same process without the need to design additional operational sessions, reducing the algorithm’s resource consumption.In addition, the correctness of the algorithm was verified by comparing the corresponding round state values, and the security of the algorithm was analyzed using various analysis methods such as linear attacks and sliding attacks.Finally, the algorithm was implemented in C language to prove the AEUR has good performance.The results show that the proposed algorithm has a better overall performance in terms of software runtime, with efficiency improvements of 3% and 46% compared to AEGIS and ALE, and 74% and 92% compared to AES-GCM and ACORN, respectively.

Abstract Objectives Gut microbiota is relevant to the pathogenesis of mental disorders including depression. This study aimed to investigate the influence of fluoxetine (FLX) on the gut microbiota in rats with Chronic Unpredictable Mild Stresses (CUMS)-induced depression. Results We confirmed that the 28-day CUMS-induced depression rat model. Chronic FLX administration weakly improved depressive-like behaviors in rats. Illumina 16S rRNA gene sequencing on rat feces showed CUMS increased the relative abundance of Firmicutes (60.31% vs. 48.09% in Control, p

Abstract Background Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Vitro experiments have shown that adding cytokines can help DPSCs to be transformed from multipotent stem cells to osteoblasts. TGF-β has been proved to have an effect on the proliferation and mineralization of bone tissue, but its effect on the osteogenesis and proliferation of dental pulp stem cells is still uncertain. We aim to determine the effect of TGF-β on the osteogenesis and proliferation of dental pulp stem cells. Methods We have identified studies from the Cochrane Central Register of Controlled Trials, PubMed, Embase, and China national knowledge infrastructure (CNKI) for studies interested in TGF-β and proliferation and differentiation of dental pulp stem cells in the following indicators: A490 (an index for evaluating cell proliferation), bone sialoprotein (BSP), Col plasmid-1 (Col-1), osteocalcin (OCN), runt-related transcription factor 2 (Runx-2); and the number of mineralized nodules. Any language restrictions were rejected. Furthermore, we drew a forest plot for each outcome. We conducted a sensitivity analysis, data analysis, heterogeneity, and publication bias test. We evaluate the quality of each study under the guidance of Cochrane's tool for quality assessment. Results The pooled data showed that TGF-β could promote the proliferation and ossification of dental pulp stem cells. All the included results support this conclusion except for the number of mineralized nodules: TGF-β increases the A490 index (SMD 3.11, 95% CI [0.54–5.69]), promotes the production of BSP (SMD 3.11, 95% CI [0.81–6.77]), promotes the expression of Col-1 (SMD 4.71, 95% CI [1.25–8.16]) and Runx-2 (SMD 3.37, 95% CI [− 0.63 to 7.36]), increases the content of OCN (SMD 4.32, 95% CI [1.20–7.44]) in dental pulp, and has no significant effect on the number of mineralized nodules (SMD 3.87, 95% CI [− 1.76 to 9.51]) in dental pulp stem cells. Conclusions TGF-β promotes the proliferation and osteogenesis of dental pulp stem cells.