Search

Simple Summary: The reproduction of goats is a highly complex and dynamic process of life regulation, which is synergistically regulated by various aspects such as central nervous system regulation, reproductive system development, oocyte maturation, and fertilized egg development. In goats, there is still an urgent need to explore marker genes related to reproductive performance. This study identified the RPL4 gene as a key marker gene related to reproductive capacity in goat oocytes through various bioinformatics analysis methods including WGCNA, PPI network analysis, and differential gene expression analysis. The results reveal that the RPL4 gene in oocytes has the potential to serve as a biological marker for determining the reproductive rate of goats, deepening our understanding of the regulatory mechanisms of goat reproductive performance. Reproduction in goats is a highly complex and dynamic process of life regulation, involving coordinated regulation from various aspects such as central nervous system regulation, reproductive system development, oocyte maturation, and fertilized egg development. In recent years, researchers have identified numerous genes associated with goat reproductive performance through high-throughput sequencing, single-cell sequencing, gene knockout, and other techniques. However, there is still an urgent need to explore marker genes related to goat reproductive performance. In this study, a single-cell RNA sequencing dataset of oocytes (GSE136005) was obtained from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to identify modules highly correlated with goat litter size. Through gene function enrichment analysis, it was found that genes within the modules were mainly enriched in adhesive junctions, cell cycle, and other signaling pathways. Additionally, the top 30 hub genes with the highest connectivity in WGCNA were identified. Subsequently, using Protein–Protein Interaction (PPI) network analysis, the top 30 genes with the highest connectivity within the modules were identified. The intersection of hub genes, key genes in the PPI network, and differentially expressed genes (DEGs) led to the identification of the RPL4 gene as a key marker gene associated with reproductive capacity in goat oocytes. Overall, our study reveals that the RPL4 gene in oocytes holds promise as a biological marker for assessing goat litter size, deepening our understanding of the regulatory mechanisms underlying goat reproductive performance. [ABSTRACT FROM AUTHOR]

mRNA vaccines are attractive prospects for the development of DC-targeted vaccines; however, no clinical success has been realized because, currently, it is difficult to simultaneously achieve DC targeting and efficient endosomal/lysosomal escape. Herein, we developed a sialic acid (SA)-modified mRNA vaccine that simultaneously achieved both. The SA modification promoted DCs uptake of lipid nanoparticles (LNPs) by 2 times, >90% of SA-modified LNPs rapidly escaped from early endosomes (EEs), avoided entering lysosomes, achieved mRNA simultaneously translated in ribosomes distributed in the cytoplasm and endoplasmic reticulum (ER), significantly improved the transfection efficiency of mRNA LNPs in DCs. Additionally, we applied cleavable PEG-lipids in mRNA vaccines for the first time and found this conducive to cellular uptake and DC targeting. In summary, SA-modified mRNA vaccines targeted DCs efficiently, and showed significantly higher EEs/lysosomal escape efficiency (90% vs 50%), superior tumor treatment effect, and lower side effects than commercially formulated mRNA vaccines. The SA-modified mRNA vaccine prepared by microfluidic mixture synchronously realizes DCs targeted and efficient EEs and lysosome escape, activates the immune system to eliminate tumors. [Display omitted] • Simultaneously achieving DC targeting and efficient endosomal/lysosomal escape. • First to apply sialic acid- lipid derivative and cleavable PEG-lipid on mRNA LNPs. • Constructed a new computational model to evaluate the transfection efficiency of mRNA delivery vectors. • SA modification significantly improved the antitumor efficacy of mRNA vaccine, and has fewer side effects. [ABSTRACT FROM AUTHOR]

Response process data collected from human–computer interactive items contain detailed information about respondents' behavioural patterns and cognitive processes. Such data are valuable sources for analysing respondents' problem‐solving strategies. However, the irregular data format and the complex structure make standard statistical tools difficult to apply. This article develops a computationally efficient method for exploratory analysis of such process data. The new approach segments a lengthy individual process into a sequence of short subprocesses to achieve complexity reduction, easy clustering and meaningful interpretation. Each subprocess is considered a subtask. The segmentation is based on sequential action predictability using a parsimonious predictive model combined with the Shannon entropy. Simulation studies are conducted to assess the performance of the new method. We use a case study of PIAAC 2012 to demonstrate how exploratory analysis for process data can be carried out with the new approach. [ABSTRACT FROM AUTHOR]

Objective: To critically review the literature regarding workplace breast-feeding interventions and to assess their impact on breast-feeding indicators.Design: A systematic review and meta-analysis was conducted. Electronic searches for workplace intervention studies to support breast-feeding, without restriction on language or study design, were performed in PubMed, CENTRAL, CINAHL, Embase, Web of Science, Business Source Complete, ProQuest-Sociology and ProQuest-Social Science to 13 April 2020. A meta-analysis of the pooled effect of the programmes on breast-feeding indicators was conducted.Results: The search identified 10 215 articles; fourteen studies across eighteen publications met eligibility criteria. Programmes were delivered in the USA (n 10), Turkey (n 2), Thailand (n 1) or Taiwan (n 1). There were no randomised controlled trials. The pooled OR for exclusive breast-feeding at 3 or 6 months for participants v. non-participants of three non-randomised controlled studies was 3·21 (95 % CI 1·70, 6·06, I2 = 22 %). Despite high heterogeneity, other pooled outcomes were consistently in a positive direction with acceptable CI. Pooled mean duration of breast-feeding for five single-arm studies was 9·16 months (95 % CI 8·25, 10·07). Pooled proportion of breast-feeding at 6 months for six single-arm studies was 0·76 (95 % CI 0·66, 0·84) and breast-feeding at 12 months for three single-arm studies was 0·41 (95 % CI 0·22, 0·62). Most programmes were targeted at mothers; two were targeted at expectant fathers.Conclusions: Workplace programmes may be effective in promoting breast-feeding among employed mothers and partners of employed fathers. However, no randomised controlled trials were identified, and better-quality research on workplace interventions to improve breast-feeding is needed. [ABSTRACT FROM AUTHOR]

Computer simulations have become a popular tool for assessing complex skills such as problem‐solving. Log files of computer‐based items record the human–computer interactive processes for each respondent in full. The response processes are very diverse, noisy, and of non‐standard formats. Few generic methods have been developed to exploit the information contained in process data. In this paper we propose a method to extract latent variables from process data. The method utilizes a sequence‐to‐sequence autoencoder to compress response processes into standard numerical vectors. It does not require prior knowledge of the specific items and human–computer interaction patterns. The proposed method is applied to both simulated and real process data to demonstrate that the resulting latent variables extract useful information from the response processes. [ABSTRACT FROM AUTHOR]

Glycogen is an essential nutritional component of the Pacific abalone (Haliotis discus hannai), and its content is a crucial factor in selecting and breeding high-quality abalone. Glycogen catabolism is facilitated by two key enzymes: glycogen debranching enzyme (GDE) and glycogen phosphorylase (GP). This study aimed to explore the relationship between GDE and GP gene polymorphisms and glycogen content in abalone. To this end, four and two SNP loci located in the exonic regions of these two genes, respectively, were screened and identified in 264 abalone using direct sequencing. The results of genetic polymorphism and correlation analysis revealed a negative correlation between the expression of GDE and GP and glycogen content. Moreover, the study found that the GA haplotype of GDE gene SNP1/3 was significantly associated with high glycogen content, while the TT genotype of GP gene SNP2 was significantly associated with low glycogen content. These results provide molecular markers that could be utilized for selecting and breeding glycogen traits in abalone, indicating the potential influence of GDE and GP polymorphisms on glycogen content. • Glycogen content in 264 samples of H. discus hannai showed a normal distribution. • The expressions of GDE and GP were negatively correlated with glycogen content. • The GA haplotype of SNP1/3 in GDE was strongly associated with high glycogen content. • The TT genotype of SNP2 in GP was strongly associated with low glycogen content. [ABSTRACT FROM AUTHOR]

Many surveillance systems of infectious diseases are syndrome-based, capturing patients by clinical manifestation. Only a fraction of patients, mostly severe cases, undergo laboratory validation to identify the underlying pathogen. Motivated by the need to understand transmission dynamics and associate risk factors of enteroviruses causing the hand, foot, and mouth disease (HFMD) in China, we developed a Bayesian spatio-temporal modeling framework for surveillance data of infectious diseases with small validation sets. A novel approach was proposed to sample unobserved pathogen-specific patient counts over space and time and was compared to an existing sampling approach. The practical utility of this framework in identifying key parameters was assessed in simulations for a range of realistic sizes of the validation set. Several designs of sampling patients for laboratory validation were compared with and without aggregation of sparse validation data. The methodology was applied to the 2009 HFMD epidemic in southern China to evaluate transmissibility and the effects of climatic conditions for the leading pathogens of the disease, enterovirus 71, and Coxsackie A16. for this article are available online. [ABSTRACT FROM AUTHOR]

IκB-related kinase ε (IKKε) plays a crucial role in the activation of nuclear factor κB (NF-κB) by phosphorylating inhibitor of NF-κB (IκB) and in the regulation of interferon (IFN) gene expression by phosphorylating IFN regulatory factors (IRFs). In this study, we cloned an IKKε homologue cDNA (designated as CgIKKε-like) from the Pacific oyster, Crassostrea gigas. The full 2896-bp cDNA sequence comprised a 2163-bp open reading frame (ORF) encoding 720 amino acids. CgIKKε-like is ubiquitously expressed, and its mRNA levels in hemocytes after poly I:C, V. alginolyticus , or OsHV-1 μVar challenge were analyzed by real-time PCR. Compared to that in the control, CgIKKε-like mRNA expression levels were significantly increased at 3 h and peaked at 6 h after OsHV-1 μVar challenge; no obvious changes were observed in expression levels until 24 h after either V. alginolyticus or poly I:C challenge, reaching a maximum at 24 h (p < 0.01) and then rapidly decreasing. CgIKKε-like transfection into human cell lines induced NF-κB and ISRE activation, while transfection with CgIKKε-like deletion mutants abolished NF-κB and ISRE reporter gene activation. Additionally, CgIKKε-like could interact with CgTBK1 and could form homodimers strongly, which may be critical for the immune signaling transduction. Last but not least, we found that CgIKKε-like may increase CgIκBs phosphorylation and could interact with CgIRF8. Together, these results suggest that CgIKKε-like could respond to pathogenic infection, participate in the immune signal transduction and activate NF-κB and ISRE reporter genes. Thus, CgIKKε-like could play an important role in the oyster immune system. • An IKKε-like gene was identified in the Pacific oyster Crassostrea gigas. • CgIKKε-like mRNA expression was induced after viral and bacterial challenge. • CgIKKε-like could induce NF-κB and ISRE activation in human cell lines. • CgIKKε-like interacts with CgTBK1 and forms homodimers strongly. • CgIKKε-like interacts with CgIRF8 and may phosphorylate CgIκBs. [ABSTRACT FROM AUTHOR]

Understanding the factors influencing urban water use is critical for meeting demand and conserving resources. To analyze the relationships between urban household-level water demand and potential drivers, we develop a method for Bayesian variable selection in partially linear additive regression models, particularly suited for high-dimensional spatio-temporally dependent data. Our approach combines a spike-and-slab prior distribution with a modified version of the Bayesian group lasso to simultaneously perform selection of null, linear, and nonlinear models and to penalize regression splines to prevent overfitting. We investigate the effectiveness of the proposed method through a simulation study and provide comparisons with existing methods. We illustrate the methodology on a case study to estimate and quantify uncertainty of the associations between several environmental and demographic predictors and spatio-temporally varying household-level urban water demand in Tampa, FL. [ABSTRACT FROM AUTHOR]

Personalized learning refers to instruction in which the pace of learning and the instructional approach are optimized for the needs of each learner. With the latest advances in information technology and data science, personalized learning is becoming possible for anyone with a personal computer, supported by a data‐driven recommendation system that automatically schedules the learning sequence. The engine of such a recommendation system is a recommendation strategy that, based on data from other learners and the performance of the current learner, recommends suitable learning materials to optimize certain learning outcomes. A powerful engine achieves a balance between making the best possible recommendations based on the current knowledge and exploring new learning trajectories that may potentially pay off. Building such an engine is a challenging task. We formulate this problem within the Markov decision framework and propose a reinforcement learning approach to solving the problem. [ABSTRACT FROM AUTHOR]

Small area estimation is becoming increasingly popular for survey statisticians. One very important program is Small Area Income and Poverty Estimation undertaken by the United States Bureau of the Census, which aims at providing estimates related to income and poverty based on American Community Survey data at the state level and even at lower levels of geography. This article introduces global-local (GL) shrinkage priors for random effects in small area estimation to capture wide area level variation when the number of small areas is very large. These priors employ two levels of parameters, global and local parameters, to express variances of area-specific random effects so that both small and large random effects can be captured properly. We show via simulations and data analysis that use of the GL priors can improve estimation results in most cases. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement. [ABSTRACT FROM AUTHOR]

MyD88 is a universal adapter protein for the Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) signaling pathway. Since invertebrates are believed to lack MyD88-independent pathways, MyD88 appears more critical in oyster TLR signaling pathway. In the Pacific oyster (Crassostrea gigas), two complete paralogues, named as CgMyD88-1 and CgMyD88-2 , have been identified. In the current study, we indicated that CgMyD88-1 and CgMyD88-2 might act synergistically to increase the efficiency of immune signaling by activating NF-κB transcription factor. However, we found that upon stimulation with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid [poly (I:C)], CgMyD88-1 and CgMyD88-2 show differences in their response: CgMyD88-1 accumulated as large spots in the cytoplasm, while CgMyD88-2 assembled in the cytoplasm and in the membrane. Our results support the theory that expansion of these immune genes is associated with functional diversity. • CgMyD88-1 and CgMyD88-2 synergistically interact in CgTLR3-mediated immunity pathway. • CgMyD88-1 and CgMyD88-2 activate NF-κB transcription factor. • CgMyD88-1 and CgMyD88-2 show differential response upon LPS or poly (I:C) stimulation. • Expansion of MyD88 genes is associated with functional diversity in invertebrates. [ABSTRACT FROM AUTHOR]

Interleukin-1 receptor-associated kinases (IRAKs) play important roles in MyD88-dependent TLR signaling, the crucial innate immune pathway in molluscs. In this study, we examined the full-length IRAK4 genetic sequence in the Pacific oyster ( Crassostrea gigas ) by molecular cloning. Phylogenetic analysis revealed that CgIRAK4 is most closely related to Mytilus edulis , and forms a clade with other molluscs. CgIRAK4 transcripts are widely expressed in all tissues, with the highest expression observed in the hemocytes and gill. Moreover, CgIRAK4 is significantly upregulated after Oyster herpesvirus-1 microvariant (OsHV-1 μvar), Vibrio alginolyticus , and poly I:C challenge. Yeast two-hybrid and co-immunoprecipitation assays reveal that the CgIRAK4 death domain is necessary to mediate interaction between CgIRAK4 and two CgMyD88 isoforms. In addition, CgIRAK4 overexpression cannot induce NF-κB transcriptional activity, but blocks that induced by CgMyD88 in HEK293T cells. These findings elucidate the mechanisms of MyD88-dependent TLR signaling in molluscs, and the differences in IRAK-mediated pathway activation between invertebrates and vertebrates. [ABSTRACT FROM AUTHOR]

As a benthic filter feeder of estuaries, the immune system of oysters provides one of the best models for studying the genetic and molecular basis of the innate immune pathway in marine invertebrates and examining the influence of environmental factors on the immune system. Here, the molecular function of molluscan TANK-binding kinase-1 (TBK1) (which we named CgTBK1) was studied in the Pacific oyster, Crassostrea gigas . Compared with known TBK1 proteins in other model organisms, CgTBK1 contains a conserved S-TKc domain and a coiled coil domain at the N- and C-terminals but lacks an important ubiquitin domain. Quantitative real-time PCR analysis revealed that the expression level of CgTBK1 was ubiquitous in all selected tissues, with highest expression in the gills. CgTBK1 expression was significantly upregulated in response to infections with Vibrio alginolyticus , ostreid herpesvirus 1 (OsHV-1 reference strain and μvar), and polyinosinic:polycytidylic acid sodium salt, suggesting its broad function in immune response. Subcellular localization showed the presence of CgTBK1 in the cytoplasm of HeLa cells, suggesting its potential function as the signal transducer between the receptor and transcription factor. We further demonstrated that CgTBK1 interacted with CgSTING in HEK293T cells, providing evidence that CgTBK1 could be activated by direct binding to CgSTING. In summary, we characterized the TBK1 gene in C. gigas and demonstrated its role in the innate immune response to pathogen infections. [ABSTRACT FROM AUTHOR]

[Display omitted] Combined administration of drugs can improve efficacy and reduce toxicity; therefore, this combination approach has become a routine method in cancer therapy. The main combination regimens are sequential, mixed (also termed "cocktail"), and co-loaded; however, other combinations, such as administration of synergistic drugs and the use of formulations with different mechanisms of action, may exert better therapeutic effects. Tumor-associated macrophages (TAMs) play functional roles throughout tumor progression and exhibit characteristic phenotypic plasticity. Sialic acid (SA)-modified epirubicin liposomes (S-E-L) and SA-modified zoledronate liposomes (S-Z-L) administered separately kill TAMs, reverse their phenotype, and achieve antitumor effects. In this study, we examined the effects of a two-treatment combination for drug delivery, using sequential, mixed, and co-loaded drug delivery. We found that therapeutic effects differed between administration methods: mixed administration of S-E-L and S-Z-L, co-loaded administration of SA-modified liposomes (S-ZE-C), and sequential administration of S-E-L injected 24 h after S-Z-L did not inhibit tumor growth; however, sequential administration of S-Z-L injected 24 h after S-E-L resulted in no tumor growth, no toxicity to noncancerous tissue, and no death of mice, and exhibited 25% tumor shedding. Thus, our results thus encourage the further development of combined therapies for nanomedicines based on the mechanisms investigated here. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs), like monoclonal antibodies of PD-1, CTLA-4, and their ligands, are effective only in some populations of patients with cancer, because the immunosuppressive state of the tumor microenvironment (TME) in some patients cannot be effectively reversed after ICI therapy. Sialic acid (SA) receptors in the Siglec family are highly expressed on the surface of tumor-associated macrophages (TAMs) and most have immunosuppressive effects. Therefore, targeting TAMs (the siglec axis) to reverse tumor immunosuppression may provide a new direction for the development of novel tumor immunotherapies. We designed a Zoledronic acid (ZA)-loaded liposome modified by a SA–octadecylamine conjugate (ZA-SL) to act as a novel nanomedicine delivery platform. This platform can efficiently deliver ZA to TAMs through the combination of SA and Siglec-1 and exerts specific cytotoxicity or phenotypic remodeling of M2-like TAMs depending on the drug concentration in TAMs. In vivo experiments showed that ZA-SL had good TAM targeting ability, and after treatment, the S180 tumors of mice were significantly inhibited, and the proportion of M1-like TAMs was significantly higher than that of M2-like TAMs with no significant adverse reactions in mice. Therefore, SA-modified ZA-loaded liposomes may provide a promising strategy for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

In different types of cancer treatments, cancer-specific T cells are required for effective anticancer immunity, which has a central role in cancer immunotherapy. However, due to the multiple inhibitions of CD8+ T cells by tumor-related immune cells, CD8+ T-cell mediated antitumor immunotherapy has not achieved breakthrough progress in the treatment of solid tumors. Receptors for sialic acid (SA) are highly expressed in tumor-associated immune cells, so SA-modified nanoparticles are a drug delivery nanoplatform using tumor-associated immune cells as vehicles. To relieve the multiple inhibitions of CD8+ T cells by tumor-associated immune cells, we prepared SA-modified doxorubicin liposomes (SL-DOX, Scheme 1A). In our study, free SA decreased the toxicity of SL-DOX to tumor-associated immune cells. Compared with common liposomes, SL-DOX could inhibit tumor growth more effectively. It is worth noting that SL-DOX could not only kill tumor-related neutrophils and monocytes to relieve the multiple inhibitions of CD8+ T cells but also induce immunogenic death of tumor cells to promote the infiltration and differentiation of CD8+ T cells (Scheme 1B). Therefore, SL-DOX has potential value for the clinical therapeutic effect of CD8+ T cells mediating anti-tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the potential of sialic acid - related selectin targeting strategy in the treatment of leukemia and some solid tumors. We expected it could "actively" bind tumor cells and kill them, reducing non-specific toxicity to normal cells. Methods: BOR-SA prodrug was synthesized by reacting an ortho-dihydroxy group in SA with a boronic acid group in BOR. Two kinds of leukemia cells (RAW264.7 and HL60 cells), one solid sarcoma cell model (S180 cells) and their corresponding normal cells (monocytes (MO), neutrophil (NE) and fibroblast (L929)) were selected for the in vitro cell experiments (cytotoxicity, cellular uptake, cell cycle and apoptosis experiments). The S180 tumor-bearing Kunming mice model was established for anti-tumor pharmacodynamic experiments. Results: In vitro cell assay results showed that uptake of BOR-SA by HL60 and S180 cells were increased compared with the control group. BOR-SA induced a lower IC50, higher ratio of apoptosis and cell cycle arrest of tumor cells. In vivo anti-S180 tumor pharmacodynamics experiments showed that mice in the BOR-SA group had higher tumor inhibition rate, higher body weight and lower immune organ toxicity compared with the control group. Conclusions: sialic acid-mediated selectin targeting strategy may have great potential in the treatment of related tumors. [ABSTRACT FROM AUTHOR]

The Junggar Basin was an intracontinental basin enclosed by multiple orogenies in the Mesozoic. Unravelling the provenances development in the western Junggar Basin enclosed by the West Junggar Orogenic Belt (WJOB) and Tianshan Orogenic Belt (TSOB) would elucidate the exhumation history of these orogenic belts during the post-orogenic period. The TSOB includes Central Tianshan which includes a continental block with the Precambrian to early Palaeozoic metamorphic basements, while the WJOB includes Palaeozoic accretionary complexes. Given their contrasting geological histories, we use detrital garnets, metamorphic ilmenites, epidotes, and Precambrian zircons to distinguish the TSOB and detrital Cr-spinel to distinguish the WJOB. Combined with sedimentary analysis, palaeocurrents, heavy mineral data, seismic profiles, and zircon U-Pb geochronology, here we reconstruct a four-phase source-to-sink model. During the syn-rift phase, the southern basin was stably fed by the TSOB in the Triassic, evidenced by high Garnet-zircon index and stable single-peak Carboniferous detrital zircon age spectra. During the post-rift sag basin phase, the source-to-sink system experienced a significant change, because detrital zircon age spectra change into multiple peaks. During the transpressional basin phase, the WJOB replaced the TSOB as the dominant provenance in the late Middle Jurassic and the TSOB became the dominant provenance again in the Late Jurassic. Syndepositional volcanic materials provided a large amount of sediments. During the sag basin phase, lake transgression happened and the TSOB provenance could not reach the northern basin. We concluded that the WJOB experienced transpression and obvious denudation in the late Middle Jurassic, and the TSOB uplifted under transpression in the Late Jurassic. The transpression controlled the change of major provenances. The aridification in the Late Jurassic was recorded by the decrease in the Zircon-Tourmaline-Rutile index and the increase in epidotes and magnetites. The humidification in the Early Cretaceous was responded to by lake transgression and sediment recycling. [ABSTRACT FROM AUTHOR]

Sensitive and specific detection of DNA is of great significance for clinical diagnosis. In this paper, an effective cascade signal amplification strategy was introduced into photoelectrochemical (PEC) biosensor for ultrasensitive detection of human T-cell lymphotropic virus type I (HTLV-I) DNA. This proposed signal amplification strategy integrates λ-exonuclease (λ-Exo) aided target recycling with hybridization chain reaction (HCR) and enzyme catalysis. In the presence of target DNA (tDNA) of HTLV-I, the designed hairpin DNA (h 1 DNA) hybridized with tDNA, subsequently recognized and cleaved by λ-Exo to set free tDNA. With the λ-Exo aided tDNA recycling, an increasing number of DNA fragments (output DNA, oDNA) were released from the digestion of h 1 DNA. Then, triggered by the hybridization of oDNA with capture DNA (cDNA), numerous biotin-labeled hairpin DNAs (h 2 DNA and h 3 DNA) could be loaded onto the photoelectrode via the HCR. Finally, avidin-labeled alkaline phosphatase (avidin-ALP) could be introduced onto the electrode by specific interaction between biotin and avidin. The ALP could catalyze dephosphorylation of phospho-L-ascorbic acid trisodium salt (AAP) to generate an efficient electron donor of ascorbic acid (AA), and thereby greatly increasing the photocurrent signal. By utilizing the proposed cascade signal amplification strategy, the fabricated PEC biosensor exhibited an ultrasensitive and specific detection of HTLV-I DNA down to 11.3 aM, and it also offered an effective strategy to detect other DNAs at ultralow levels. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper was to investigate the effects of SO42− concentration on the corrosion behaviour of T23 and T12 steels in simulated water chemistry condition solution of 600 MW fossil-fired power boilers. Design/methodology/approach – The influence and mechanism of SO42− ions on the pitting corrosion of T23 and T12 steels in simulated oxygenated treatment water chemistry solution was studied using electrochemical potentiodynamic polarization scans and electrochemical impedance spectroscopy. Findings – The results showed that T23 and T12 were susceptible to pitting corrosion in the simulated solution with full SO42− concentration for the competitive adsorption of OH− and SO42− on the surface of steels. The pitting sensitivity of the steels improved with increasing SO42− concentration. The corrosion resistance for SO42− of T23 was stronger than that for T12. Originality/value – This study is an attempt to provide direction for regulating the concentration of SO42− in boiler water and for selecting the material for boiler water wall tubes. [ABSTRACT FROM AUTHOR]

• Six lacustrine carbonate microfacies in the Lower Cretaceous Junggar Basin are identified. • A semi-open, shallow, and hydrologically partitioned lake in the Early Cretaceous. • Aridificaiton led to transition from hydrologically partitioned to integrated lake. We report sedimentary microfacies analysis of Lower Cretaceous algal-laminated limestones interbedded with siliciclastic sediments in the Junggar Basin. We use these data to fill a knowledge gap in the Jurassic–Late Cretaceous paleoenvironmental and paleoclimate reconstructions of Central Asia. To decipher paleoenvironments and genetic mechanisms, we applied optical petrography, cathodoluminescence and fluorescence imaging, Raman spectroscopy, stable isotopic, and scanning electron microscopic analysis. Some oncoids exhibit alternating dark organic carbon-rich micrites and light sparry calcite laminae with unequal thicknesses and binding structures of microbiota. Formed by both algal binding and inorganic calcite precipitation, in-situ mixing happened during the formation of oncoidal, ooidal, and ostracodal grainstones in an agitated lakeshore and thromobolites in a relatively low-energy environment. Sparry carbonate cortices peeled off from the oncoids were transported to the shallow lake and densely packed with micrites and mud. Based on the degree of covariance between δ18O and δ13C and the wide range of δ18O, the paleo-lake was inferred to be a semi-open, shallow, and hydrologically partitioned lake in the Early Cretaceous, but evolved into a closed but well-mixed lake in the Late Cretaceous. We infer that this change is caused by the aridification in the Late Cretaceous. The Early Cretaceous lacustrine carbonates in the Junggar Basin show overall more positive δ13C than the counterparts in the Upper Cretaceous, which is attributed to the 12CO 2 absorption by microbiota. Sulfate reduction is revealed by negative sulfur isotopes of concomitant thin-layered gypsums but it exerts no measurable impact on the δ13C of the carbonates. [ABSTRACT FROM AUTHOR]

In preclinical studies of young mice, nanoparticles showed excellent anti-tumor therapeutic effects by harnessing Peripheral Blood Monocytes (PBMs) and evading the immune system. However, the changes of age will inevitably affect PBMs and the immune system, and there is a serious lack of relevant research. Sialic acid (SA)-octadecylamine (ODA) was synthesized, and SA- or polyethylene glycol (PEG)-modified epirubicin (EPI) liposomes (EPI-SL and EPI-PL, respectively) were prepared to explore differences in antitumor treatment using 8-month-old and 8-week-old Kunming mice. Based on presented data, 8-month-old mice had more PBMs in peripheral blood than 8-week-old mice, and age differences resulted in different anti-tumor treatment effects following EPI-SL and EPI-PL treatment. Following EPI-PL administration, the tumor volume was significantly smaller in 8-week-old mice than in 8-month-old mice (* p < 0.05). Eight-month-old mice treated with EPI-SL (8M-SL) presented no damage to healthy tissue, with a 100% survival rate, and 50% mice in 8M-SL showed 'shedding' of tumor tissues from the growth site. Accordingly, 8-month-old mice treated with EPI-SL achieved the best therapeutic effect at different ages and with different liposomes. EPI-SL could improve the antitumor effect of 8-week-old and 8-month-old mice. [ABSTRACT FROM AUTHOR]

The accelerated blood clearance (ABC) phenomenon describes a dilemma of polyethylene glycol (PEG) applied in drug delivery system (DDS) caused by its immunogenicity, that results in the enhanced blood clearance rate and increased hepatic and splenic accumulation after secondary injection of PEGylated nanocarriers. However, the ABC index, as the judgement of ABC phenomenon, only describes the accelerated blood clearance rate, but ignores the enhanced hepatic and splenic accumulation. Therefore, we proposed the hepatic accumulation (HA) index and the splenic accumulation (SA) index as supplements for assessing the ABC phenomenon, to emphasize the contribution of liver and spleen, especially the liver, possessing the most population of tissue resident macrophages. By altering the first injection site from the tail vein to the liver portal vein, there was no impact on anti-PEG IgM production, and the secondary hepatic accumulation of PEGylated nanoemulsions (PE) was observed to be proportionate to the first PE stimulation strength on the liver. We also determined that Kupffer cells (KCs) were the main contributor to this enhancement. On this basis, we revealed a definite phenomenon that PE could induce innate immune memory in KCs, by enhancing the phagocytosis of KCs toward PE during the secondary stimulation. The PE-stimulated KCs could carry this memory to the naïve rats through adoptive transfer, resulting in increased hepatic accumulation in the recipient rats without antibody production. Studies examining the phagocytosis of KCs in vivo , ex vivo and in vitro revealed that the memory of KCs against PE triggered by first-stimulated PE could be maintained independently of other cells or components until 21 days after the first stimulation, and possessing specificity to PEG, which was invalid to long-circulating GE (GM1 modified nanoemulsions). The discovery of immune memory in KCs induced by PE highlights the importance of focusing on the relationship between the innate immune system and PEGylated nanocarriers during the development of DDS to improve medication safety in the clinic. [Display omitted] • Hepatic accumulation (HA) index and the splenic accumulation (SA) index emphasize innate organs' contribution in ABC phenomenon • Kupffer cells can establish innate immune memory induced by PEGylated nanoemulsions independent of other components in body • Kupffer cells' memory results in enhanced secondary phagocytosis of PE, is specific to PEG and can maintain until 21 days [ABSTRACT FROM AUTHOR]

The terrestrial sequence stratigraphy in proximal terrestrial environments is different from its counterpart in distal terrestrial and marine environments. The Southern Junggar Basin in NW China has preserved well‐exposed proximal terrestrial outcrops and its Jurassic–Cretaceous sequence boundary remains contentious. The goal of this paper is to (a) establish a model of allogenic‐controlling mechanisms of a proximal terrestrial sequence, (b) investigate the Jurassic–Cretaceous sequence boundary, (c) the Jurassic climate, and (d) tectonic movements in Central Asia. The sequence stratigraphic framework was established assisted by the determination of the accommodation space/sediment supply (A/S) ratio, including two second‐order sequences (SS) and six third‐order sequences (SQ) in the Jurassic, as well as a second‐order sequence in the Cretaceous. SS1 was mainly controlled by a warm and humid climate and lake level fluctuations in a weak extensional tectonic setting; SS2 was mainly controlled by an arid climate and compressional tectonic movements; SS3 was mainly controlled by a semi‐humid climate and lake transgression in a stable tectonic setting. Additionally, the Jurassic–Cretaceous sequence boundary was distinguished within the Kalazha Formation based on its sedimentary characteristics, sedimentary evolution, and different allogenic controls. It is concluded that the proximal terrestrial sequences exhibit rapid sedimentary facies change, thick coarse‐grained sediments, and multiple provenances. Climate, tectonic movements, and lake level fluctuation dominate in different stages of basin evolution. Moreover, the sediment supply is more emphasized, and the accommodation space/sediment supply ratio, which corresponds to different channel geometry types, plays a critical role in identifying system tracts and sequence stratigraphic surfaces. [ABSTRACT FROM AUTHOR]

Scheme 1. Schematic illustration of Persistent immune response: Twice tumor shed induced by sialic acid–modified vincristine sulfate liposomes. (A) Preparation of SA-CH-modified vincristine sulfate liposomes. (B) Schematic illustration of SA-CH-modified vincristine sulfate liposomes, which effectively target tumor-associated macrophages, improve the tumor immunosuppressive microenvironment, and induce anti-tumor immune responses. [Display omitted] Studies have shown that tumor-associated macrophages (TAMs) are crucial for the establishment and maintenance in immunosuppressive tumor immune microenvironment (TIME), which can help tumor cells to achieve immune escape and attenuate antitumor therapy. Siglecs, the receptors of sialic acid (SA), widely exist in TAMs, which could be targeted to disrupt TIME and inhibit tumor growth at the root. Therefore, a SA–modified VCR liposome was reported (VCR-SSAL). Cellular and pharmacodynamic experiments showed that VCR-SSAL exhibited strong TAMs targeting and tumor-killing ability. Interestingly, VCR-SSAL treatment induced a phenomenon in which the cancerous tissues were "fell off" from the growth site, after which the wound gradually healed. Three months after the wound healed, the mice whose tumors fell off were re-inoculated, and the tumor fell off again without treatment, with an exfoliation rate of 100%. We speculated that this special efficacy might be due to that VCR loaded in VCR-SSAL could activate adaptive immunity by inducing DNA damage, promoting cytotoxic T lymphocytes (CTLs) infiltration into tumor sites, and enhancing the antitumor immune response. Thus, this study might provide new insights into the application of traditional chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are a family of crucial adaptors, playing vital roles in mediating signal transduction in immune signaling pathways, including RIG-I-like receptor (RLR) signaling pathway. In the present study, a new TRAF family member (CgTRAF2) was identified in the Pacific oyster, Crassostrea gigas . Comparison and phylogenetic analysis revealed that CgTRAF2 could be a new member of the invertebrate TRAF2 family. Quantitative real-time PCR revealed that CgTRAF2 mRNA was highly expressed in the digestive gland, gills, and hemocytes, and it was significantly up-regulated after Vibrio alginolyticus and ostreid herpesvirus 1 (OsHV-1) challenge. The CgTRAF2 mRNA expression profile in different developmental stages of oyster larvae suggested that CgTRAF2 could function in early larval development. CgTRAF2 mRNA expression pattern, after the silence of CgMAVS (Mitochondrial Antiviral Signaling) -like , indicated that CgTRAF2 might function downstream of CgMAVS-like. Moreover, the subcellular localization analysis revealed that CgTRAF2 was localized in cytoplasm, and it may play predominately important roles in signal transduction. Collectively, these results demonstrated that CgTRAF2 might play important roles in the innate immunity and larval development of the Pacific oyster. [ABSTRACT FROM AUTHOR]

Fibrinogen-related proteins (FREPs) are a family of proteins with high sequence diversity, and they play crucial roles in invertebrate immune response. However, few studies have characterized this diversity at the whole-genome level. In the present study, approximately 190 predicted FREPs with more than 200 fibrinogen-like (FBG) domains were identified in the genome of the Pacific oyster ( Crassostrea gigas ), suggesting a historical expansion of this protein family. A sequence analysis showed high numbers of polymorphisms in C. gigas FREP (CgFREP) genes, which may contribute to the versatile immune function of FREPs. A phylogenetic analysis of molluscan FREP sequences indicated lineage-specific duplication of these genes in C. gigas . Additionally, several CgFREP mRNAs were highly expressed in the gills, digestive glands, and hemocytes. Taken together, these findings will help elucidate FREP immune function and facilitate studies of the functional validation of this gene family. [ABSTRACT FROM AUTHOR]

PEGylation is one of the most successful technologies for reducing immunogenicity, improving the stability and circulation time of nanocarriers, and has been applied in the clinic for over three decades. However, linear PEG-modified nanocarriers have been found to induce anti-PEG IgM at the first injection, which triggers the accelerated blood clearance (ABC) phenomenon upon repeated injections. Furthermore, clinical and research evidence has revealed that anti-PEG antibodies also cause serious complement activation-related pseudoallergies (CARPA), which greatly reduce the safety of linear PEGylated nanocarriers. In this study, as an alternative to linear PEG, branched PEG was selected owing to its low antigenicity. We pioneer the use of branched PEG lipid derivatives [DSPE-mPEG 2,n (n = 2, 10, and 20 kDa)] to modify nanoemulsions (PE 2,n) and liposomes (PL 2,n). Upon characterization, PE 2,n and PL 2,n showed similar physicochemical properties to linear DSPE-mPEG 2000 -modified nanocarriers in terms of size, polydispersity index (PDI), and zeta potential. However, our pharmacokinetics study surprisingly indicated that PE 2,n and PL 2,n did not induce the ABC phenomenon after repeated injection. This may be attributed to the fact that PE 2,n and PL 2,n induced noticeably lower levels of anti-PEG IgM than linear PEG-modified nanocarriers and did not activate the complement system. Furthermore, we are the first to investigate the anti-tumor efficacy of DSPE-mPEG 2,n -modified liposomal doxorubicin (DOX). The pharmacodynamic experiments showed that DSPE-mPEG 2,n -m-modified liposomal DOX had better in vivo anti-tumor effects than linear DSPE-mPEG 2000 -modified liposomes. Therefore, we speculate that DSPE-mPEG 2,n -modified nanocarriers possess promising prospects in avoiding the ABC phenomenon, reducing CARPA, and improving the anti-tumor efficacy of encapsulated drugs. Scheme 1. (A) In vivo pharmacokinetics of DSPE-mPEG 2,n -modified nanoemulsions and liposomes after repeated injections (B) In vivo anti-tumor pharmacodynamics of DSPE-mPEG 2,n -modified liposomal doxorubicin (DOX). [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] PEGylation increases the circulation time of the nanocarrier, but also triggers accelerated blood clearance (ABC) phenomenon. It is well-known that the ABC phenomenon results in shortened blood circulation and aberrant increase in liver and spleen accumulation, which greatly limits the application of PEGylated nano-preparations. For many years, researchers have been working hard to find ways to reduce or eliminate the ABC phenomenon. Previous studies have focused on PEG molecular weight and PEG alternative materials, but there has never been any research on the effect of different PEG chain types on the ABC phenomenon. Therefore, 40 kDa molecular weight of linear PEG lipid derivatives (DSPE-mPEG 40k) and branched PEG lipid derivatives (DSPE-mPEG 2,40k) were selected to modify nanoemulsions to explore the influence of distinct PEG chain types on avoiding the ABC phenomenon for the first time. We pioneer the use of linear and branched PEG lipid derivatives (DSPE-mPEG 40k and DSPE-mPEG 2,40k) to modify nanoemulsions (PE 40k and PE 2,40k). Upon characterization, PE 40k and PE 2,40k showed good physicochemical properties in the aspect of size, polydispersity index (PDI value), and zeta potential. Surprisingly, the pharmacokinetics study indicated that repeated injection of PE 40k and PE 2,40k did not trigger the ABC phenomenon. More importantly, PE 2,40k possessed a long circulation time and did not cause ABC phenomenon after repeated injection. This may be attributed to the fact that PE 2,40k induced noticeably lower anti-PEG IgM levels compared to linear PEG-modified nanocarriers and did not activate the complement system. Therefore, we speculate that DSPE-mPEG 2,40k -modified nanocarriers possess promising prospects in avoiding the ABC phenomenon, which may improve the possibility of wide application of nanoformulations. [ABSTRACT FROM AUTHOR]

• Seismic interpretation to reveal the structural styles of the northern Tianshan. • Growth strata within each structure are closely related to tectonic patterns. • Pre-Cenozoic mega fault systems mainly cause the segmentation of northern Tianshan. • Tectonics play a key role in controlling the sedimentation. Field-based mapping and subsurface interpretations of high-resolution seismic images, as well as other geophysical data, have been integrated to investigate tectonic patterns and growth strata in the northern Tianshan fold and thrust belt (NTFTB). The NTFTB formed as a result of intense deformation and uplift of the northern Tianshan region that was triggered by the far field effects of the Indo-Eurasia plate collision. The structural styles of the NTFTB vary, and are primarily classified as thick-skinned thrust nappes that involve basement rocks and thin-skinned fault-related fold structures with multiple décollement layers in the sedimentary strata. The overall NTFTB can be divided into three segments based on its structural geometry. The western segment is characterized by an intense backthrust in the northern Tianshan piedmont, with little displacement transfer into the southern Junggar Basin. In the central segment, the emergence of three rows of anticlines reveals a progressive deformation sequence and displacement transfer into the foreland through multiple décollements. In the eastern segment, the tectonic pattern is characterized by steep faults that branch forward in a narrow zone to generate intense uplift. Evidences indicate that major basement faults, paleo-uplifts, and inheritance of former structures play key roles in driving the segmentation of the NTFTB, and that secondary fault assemblages may control regional tectonic styles within each tectonic unit. Cenozoic growth strata have been observed in the NTFTB, the geometry and deformation mechanism of which are subject to the structural style in a given structure. Growth strata can also provide constraints for time of deformation in the northern Tianshan, and the Dushanzi Formation has been shown to represent clear growth in the piedmont, which indicates rapid uplift of the northern Tianshan as well as intense tectonic activity in the NTFTB in the late Miocene. The growth strata become younger within structures to the north, towards the foreland. In general, the Cenozoic evolutional process has been relatively uniform in the northern Tianshan, generally showing a forward propagation of fault splays into the foreland, and the geometry and distribution of sedimentary strata have been controlled by tectonics. [ABSTRACT FROM AUTHOR]