Search

ABSTRACT Pine wilt disease (PWD), caused by Bursaphelenchus xylophilus, severely threatens global pine forests. Monochamus alternatus is the primary vector of B. xylophilus in East Asia. Understanding the population structure and evolutionary forces of vector insects is critical for establishing effective PWD management strategies. The present work explores the genetic structure and phylogenetic relationships of 20 populations of M. alternatus from the Qinling‐Daba Mountains (QDM) in China using the mitochondria DNA dataset, supplemented by ecological niche modeling (ENM). All M. alternatus populations were categorized into three phylogeographic clusters (Clade A, Clade B, and Clade C), with Clade A and Clade B corresponding to the western and eastern QDM, respectively. The results of divergence time estimation concur with environmental changes induced by Quaternary glacial climate oscillations in QDM of China. M. alternatus populations exhibited significant genetic differentiation, with expansion in their population size. Ecological niche modeling (ENM) demonstrated that precipitation and temperature significantly influence the distribution of M. alternatus and the species is anticipated to grow into higher latitude and higher altitude regions in the future. In a nutshell, exploring the genetic structure and evolutionary dynamics of M. alternatus can provide valuable insights into the prevention and occurrence of B. xylophilus. These findings also serve as a reference for research on population differentiation and phylogeography of other species in QDM and adjacent areas.

Hormone replacement therapy (HRT) is not recommended for treating learning and memory decline in menopausal women because it exerts adverse effects by activating classic estrogen receptors ERα and ERβ. The membrane estrogen receptor G protein-coupled receptor 30 (GPR30) has been reported to be involved in memory modulation; however, the underlying mechanisms are poorly understood. Here, we found that GPR30 deletion in astrocytes, but not in neurons, impaired learning and memory in female mice. Astrocytic GPR30 depletion induced A1 phenotype transition, impairing neuronal function. Further exploration revealed that Praja1 (PJA1), a RING ubiquitin ligase, mediated the effects of astrocytic GPR30 on learning and memory by binding to Serpina3n, which is a molecular marker of neuroinflammation in astrocytes. GPR30 positively modulated PJA1 expression through the CREB signaling pathway in cultured murine and human astrocytes. Additionally, the mRNA levels of GPR30 and PJA1 were reduced in exosomes isolated from postmenopausal women while Serpina3n levels were increased in the plasma. Together, our findings suggest a key role for astrocytic GPR30 in the learning and memory abilities of female mice and identify GPR30/PJA1/Serpina3n as potential therapeutic targets for learning and memory loss in peri- and postmenopausal women.

Excessive production of nitric oxide (NO) during the lactation period of cows leads to oxidative stress and inflammatory reactions. Chitosan has enhanced effects on antioxidant and immune function, but the mechanism of this effect is unclear. The current study investigated the underlying mechanism of the protective effect chitosan oligosaccharides (COS) exert against oxidative damage of peripheral blood mononuclear cells (PBMCs) in dairy cows. PBMCs were allocated to receive one of treatments: CTR: control treatment without COS addition; COS40, COS80, COS160, and COS320 received 40, 80, 160, and 320 μg/mL of COS; PBMCs were then treated with 200 μmol/L diethylenetriamine/nitric oxide (DETA/NO) for 4 h. Compared to the CTR group, the cell viability of the COS pre-treated group increased with increasing COS concentration. The activities of antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase and the thioredoxin reductase content showed an upward trend in a dose-dependent manner and COS at a concentration of 160 μg/mL exhibited the strongest effect. COS decreased the content and gene expressions of interleukin-1β and tumour necrosis factor-α, the mRNA and protein expression and activity of the inducible nitric oxide synthase, and NO production compared with the values observed in the CTR group. The expression of genes and proteins related to the nuclear factor kappa-B (NF-κB) pathway also showed a downward trend. Based on these indicators, we concluded COS has a protective effect against oxidative damage caused by DETA/NO, and we speculated that COS may play a protective role by inhibiting the NF-κB pathway.Highlights In vitro experiments simulated changes in antioxidant and immune functions caused by increased NO in dairy cows’ PBMCs in vivo. We showed that chitosan has a protective effect against oxidative damage and a regulatory effect on immune function in vitro. The regulation of chitosan against oxidative stress and immune responses may be related to the NF-KB signalling pathway.

Monochamus alternatus is a serious trunk-boring pest and is the most important and effective vector of the pine wood nematode Bursaphelenchus xylophilus, which causes pine wilt disease. The pine wilt disease poses a serious threat to forest vegetation and ecological security in the Qinling–Daba Mountains and their surrounding areas. In order to clarify whether the population density of M. alternatus larvae is related to the host preference of M. alternatus adults, we investigated the population density of M. alternatus overwintering larvae and explored the host preference of M. alternatus adults on Pinus tabuliformis, P. armandii, and P. massoniana. The results show that the population density of M. alternatus larvae was significantly higher on P. armandii than those on P. massoniana and P. tabuliformis. The development of M. alternatus larvae was continuous according to the measurements of the head capsule width and the pronotum width. Adults of M. alternatus preferred to oviposit on P. armandii rather than on P. massoniana and P. tabuliformis. Our results indicate that the difference in the population density of M. alternatus larvae between different host plants was due to the oviposition preference of M. alternatus adults. In addition, the instars of M. alternatus larvae could not be accurately determined, because Dyar’s law is not suitable for continuously developing individuals. This study could provide theoretical basis for the comprehensive prevention and control of the pine wilt disease in this region and adjacent areas.

Depression is a frequent and serious comorbidity associated with diabetes which adversely affects prognosis and quality of life. Glucagon-like peptide-1 receptor (GLP-1R) agonists, widely used in the treatment of diabetes, are reported to exert neuroprotective effects in the central nervous system. Thus, we aim to evaluate whether GLP-1R agonist exendin-4 (EX-4) could alleviate depression-like behaviors in diabetic mice and to explore its underlying mechanism. The antidepressant effects of EX-4 were evaluated using behavioral tests in db/db mice. The effects of EX-4 on microglial pyroptosis and neuroinflammation were assessed in N9 microglial cells. EX-4 administration alleviated depression-like behaviors in diabetic db/db mice. GLP-1R activation by EX-4 significantly suppressed microglial pyroptosis and neuroinflammation by downregulation of gasdermin D (GSDMD) and interleukin (IL)-1β in diabetic mice and lipopolysaccharide (LPS)-primed N9 microglia. Mechanistically, GLP-1R activation improved mitochondrial function and promoted mitophagy by decreasing the accumulation of mitochondrial reactive oxygen species (mtROS) and intracellular ROS production. EX-4 exhibits antidepressant effects in depression associated with diabetes in diabetic mice, which may be mediated by inhibiting microglial pyroptisis via promoting mitophagy. It is supposed that GLP-1R agonists may be a promising therapy in depression associated with diabetes.

In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future.

The rapid promotion of single-cell omics in various fields has begun to help solve many problems encountered in research, including precision medicine, prenatal diagnosis, and embryo development. Meanwhile, single-cell techniques are also constantly updated with increasing demand. For some specific target cells, the workflow from droplet screening to single-cell sequencing is a preferred option and should reduce the impact of operation steps, such as demulsification and cell recovery. We developed an all-in-droplet method integrating cell encapsulation, target sorting, droplet picoinjection, and single-cell transcriptome profiling on chips to achieve labor-saving monitoring of TCR-T cells. As a proof of concept, in this research, TCR-T cells were encapsulated, sorted, and performed single-cell transcriptome sequencing (scRNA-seq) by injecting reagents into droplets. It avoided the tedious operation of droplet breakage and re-encapsulation between droplet sorting and scRNA-seq. Moreover, convenient device operation will accelerate the progress of chip marketization. The strategy achieved an excellent recovery performance of single-cell transcriptome with a median gene number over 4000 and a cross-contamination rate of 8.2 ± 2%. Furthermore, this strategy allows us to develop a device with high integrability to monitor infused TCR-T cells, which will promote the development of adoptive T cell immunotherapy and their clinical application.

The senescence of mesenchymal stem cells (MSCs) impairs their regenerative capacity to maintain tissue homeostasis. Numerous studies are focusing on the interventions and mechanisms to attenuate the senescence of MSCs. C-phycocyanin (C-PC) is reported to have multiple functions such as antitumor, antioxidation, anti-inflammation and anti-aging roles, but there is little research about the effects of C-PC on the senescence of MSCs. Here we investigated the roles and mechanism of C-PC on MSCs senescence. In vitro results showed that C-PC could reduce senescence, enhance proliferation, promote the adipogenic and osteogenic differentiation in senescent MSCs induced by oxidative stress. In vivo D-Galactose (D-Gal) induced rats aging models showed C-PC also increased the viability and differentiation of intrinsic senescent bone marrow derived MSCs (BMSCs). Furthermore, C-PC also decreased the levels of oxidative stress markers ROS or MDA, elevated the SOD activity, and increased the anti-inflammatory factors. Proteomic chip analysis showed that C-PC interacted with ZDHHC5, and their interaction was verified by pull down assay. Overexpression of ZDHHC5 aggravated the senescence of MSCs and greatly lessened the beneficial effects of CPC on senescence. In addition, we found ZDHHC5 regulated autophagy by altering LC3, Beclin1 and PI3K/AKT/mTOR pathway. In summary, our data indicated that C-PC ameliorates the senescence of MSCs through zinc finger Asp-His-His-Cys (DHHC) domain-containing protein 5 (ZDHHC5) mediated autophagy via PI3K/AKT/mTOR pathway. The present study uncovered the key role of autophagy in MSCs senescence and PI3K/AKT/mTOR pathway may be a potential target for anti-senescence studies of MSCs. [ABSTRACT FROM AUTHOR]

Abstract The introduction of porosity into ferroelectric ceramics can decrease the effective permittivity, thereby enhancing the open circuit voltage and electrical energy generated by the direct piezoelectric effect. However, the decrease in the longitudinal piezoelectric coefficient (d33) with increasing porosity levels currently limiting the range of pore fractions that can be employed. By introducing aligned lamellar pores into (Ba0.85Ca0.15)(Zr0.1Ti0.9)O3, this paper demonstrates an unusual 22–41% enhancement in the d33 compared to its dense counterpart. This unique combination of high d33 and a low permittivity leads to a significantly improved voltage coefficient (g33), energy harvesting figure of merit (FoM33) and electromechanical coupling coefficient (k332). The underlying mechanism for the improved properties is demonstrated to be a synergy between the low defect concentration and high internal polarizing field within the porous lamellar structure. This work provides insights into the design of porous ferroelectrics for applications related to sensors, energy harvesters, and actuators.

Abstract Objective To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally. Methods We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally. Result MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p

Abstract The applications of silica-based glass have evolved alongside human civilization for thousands of years. High-precision manufacturing of three-dimensional (3D) fused silica glass objects is required in various industries, ranging from everyday life to cutting-edge fields. Advanced 3D printing technologies have emerged as a potent tool for fabricating arbitrary glass objects with ultimate freedom and precision. Stereolithography and femtosecond laser direct writing respectively achieved their resolutions of ~50 μm and ~100 nm. However, fabricating glass structures with centimeter dimensions and sub-micron features remains challenging. Presented here, our study effectively bridges the gap through engineering suitable materials and utilizing one-photon micro-stereolithography (OμSL)-based 3D printing, which flexibly creates transparent and high-performance fused silica glass components with complex, 3D sub-micron architectures. Comprehensive characterizations confirm that the final material is stoichiometrically pure silica with high quality, defect-free morphology, and excellent optical properties. Homogeneous volumetric shrinkage further facilitates the smallest voxel, reducing the size from 2.0 × 2.0 × 1.0 μm3 to 0.8 × 0.8 × 0.5 μm3. This approach can be used to produce fused silica glass components with various 3D geometries featuring sub-micron details and millimetric dimensions. This showcases promising prospects in diverse fields, including micro-optics, microfluidics, mechanical metamaterials, and engineered surfaces.

Abstract Background It is generally beneficial and recommended that dichorionic triamniotic (DCTA) triplet pregnancies be reduced to monochorionic (MC) twin or singleton pregnancies after assisted reproductive technology (ART). However, some infertile couples still have a firm desire to retain twins. For this reason, the best foetal reduction strategies need to be available for infertile couples and clinicians. Given that data on the elective reduction of DCTA triplet pregnancies to twin pregnancies are scarce, we investigated the outcomes of elective reduction of DCTA triplet pregnancies through the retrospective analysis of previous data. Method Patients with DCTA triplet pregnancies who underwent elective foetal reduction between January 2012 and June 2020 were recruited. A total of 67 eligible patients with DCTA triplet pregnancies were divided into two groups: a DCTA-to-dichorionic diamniotic (DCDA) twin group (n = 38) and a DCTA-to-monochorionic diamniotic (MCDA) twin group (n = 29); the basic clinical data of the two groups were collected for comparison. Results Compared with the DCDA-to-MCDA twin group, the DCTA-to-DCDA twin group had lower rates of complete miscarriage (7.89% versus 31.03%, p = 0.014), early complete miscarriage (5.26% versus 24.14%, p = 0.034), late preterm birth (25.71% versus 65.00%, p = 0.009) and very low birth weight (0 versus 11.11%, p = 0.025). In addition, the DCTA-to-DCDA twin group had higher rates of full-term delivery (65.71% versus 25.00%, p = 0.005), survival (92.11% versus 68.97%, p = 0.023), and taking the babies home (92.11% versus 68.97%, p = 0.023) than did the DCTA-to-MCDA twin group. In terms of neonatal outcomes, a significantly greater gestational age (38.06 ± 2.39 versus 36.28 ± 2.30, p = 0.009), average birth weight (3020.77 ± 497.33 versus 2401.39 ± 570.48, p

Hepatocellular carcinoma (HCC) is still one of the leading causes of tumor-related deaths. Accumulating evidence indicates that immunogenic cell death (ICD) could occur in tumor cells. However, ICD-related studies are limited in HCC. This study collected HCC RNA sequencing data from the Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R software was used to analyze the expression of ICD in HCC and to screen essential genes with prognostic value. qRT-PCR and WB determined the mRNA and protein expressions of hub gene. Cell viability assay, Clonal formation assay, and Live/dead staining assay were employed to determine the gene functions. After cross-analysis of differentially expressed genes (DEGs) and ICD-related genes (ICDRGs), 7 differentially expressed ICDRGs were identified in HCC. Of them, HSP90AA1, with the most excellent prognostic value in HCC, was selected, whose expression was also validated in public cohorts, cell lines, and clinical tissue samples. High HSP90AA1 expression indicated an inferior prognosis of HCC, and HSP90AA1 knockdown significantly suppressed cell viability and chemotherapy resistance of HCC. ICD-related gene HSP90AA1 was an unfavorable factor for HCC, and high HSP90AA1 expression contributed to tumor cell survival and chemotherapy resistance.

IntroductionIncreased uncertainty is a major feature of the current society that poses significant challenges to university students' mental health and academics. However, current research has not paid sufficient attention to this issue, and no study has explored the underlying mechanisms between intolerance of uncertainty and academic burnout among university students.MethodsThis study examined the association between uncertainty intolerance and academic burnout among university students and the role of self-regulatory fatigue and self-compassion in light of the theory of limited resources. Convenience sampling was used to survey 1,022 Chinese university students.ResultsThe findings demonstrated that intolerance of uncertainty significantly influenced university students' academic burnout with self-regulatory fatigue serving as a key mediator. Additionally, self-compassion can effectively moderate the effects of intolerance of uncertainty on self-regulatory fatigue and academic burnout.DiscussionThese results indicated that the depletion of cognitive resources brought about by uncertainty in the current highly uncertain social environment may be one of the key pathways to academic burnout among university students. Furthermore, current research provides insights into how to mitigate the negative effects of uncertainty on university students.

IntroductionMicrobial succession and metabolic adjustment during cigar tobacco leaf (CTL) fermentation are key factors to improve the quality and flavor of CTLs. However, the interactions in the above processes remain to be further elucidated.MethodsBacillus altitudinis inoculants were added to the CTLs, and metagenomics and metabolomics were used to analyze the effects of the inoculants on regulating microbial succession, metabolic shift, and aroma production during fermentation.Results and discussionThe addition of the inoculants reinforced the CTL macromolecule transformation and facilitated the aroma production efficiently, and the total aroma production was increased by 43% compared with natural fermentation. The omics analysis showed that Staphylococcus was a main contributor to fatty acid degradation, inositol phosphate metabolism, energy supply (oxidative phosphorylation), nutrient transport (ABC transporter and phosphotransferase system [PTS]), and aroma production (terpenoid backbone biosynthesis, phenylalanine metabolism, and degradation of aromatic compounds). Furthermore, Staphylococcus was positively correlated with TCA cycle intermediates (citric acid, fumaric acid, and aconitic acid), cell wall components, peptidoglycan intermediates (GlcNAc-1-P and UDP-GlcNAc), and phytic acid degradation products (inositol). The characteristics collectively showed Staphylococcus to be the most dominant in the microbial community at the genus level during microflora succession. The addition of the inoculants supplemented the nutritional components of the CTLs, enhanced the metabolic activity and diversity of bacteria such as Corynebacterium, improved their competitive advantages in the microflora succession, and facilitated the richness of microbial communities. Additionally, a metabolic shift in nicotine degradation and NAD + anabolism from Staphylococcus to Corynebacterium in fermentation with inoculants was first observed. Meanwhile, the significantly correlative differential metabolites with Staphylococcus and Corynebacterium were a metabolic complement, thus forming a completely dynamic fermentation ecosystem. The results provided evidence for CTL fermentation optimization.

In an effort to clarify the formation mechanism of LPSO structure in Mg-Y-Zn alloy, the chemical environment and structural ordering in liquid Mg-rich Mg-Y-Zn system are investigated with the aid of ab-initio molecular dynamics simulation. In liquid Mg-rich Mg-Y alloys, the strong Mg-Y interaction is determined, which promotes the formation of fivefold symmetric local structure. For Mg-Zn alloys, the weak Mg-Zn interaction results in the fivefold symmetry weakening in the liquid structure. Due to the coexistence of Y and Zn, the strong attractive interaction is introduced in liquid Mg-Y-Zn ternary alloy, and contributes to the clustering of Mg, Y, Zn launched from Zn. What is more, the distribution of local structures becomes closer to that in pure Mg compared with that in binary Mg-Y and Mg-Zn alloys. These results should relate to the origins of the Y/Zn segregation zone and close-packed stacking mode in LPSO structure, which provides a new insight into the formation mechanism of LPSO structure at atomic level.

The formation criteria of the LPSO phase are important for the design of long-period stacking-ordered (LPSO) Mg alloys. This work focuses on Type I LPSO Mg-Y-X alloys and attempts to explore the formation criteria of the LPSO phase from the perspective of liquid-solid correlation. With the aid of ab-initio molecular dynamics simulation, liquid Mg-Y-X alloys are investigated to obtain the common liquid characteristics from the reported Type I LPSO Mg-Y-X alloys. Following the liquid characteristics, a new Type I LPSO alloy, i.e., Mg-Y-Au, is experimentally confirmed. The discovery of a new Type I LPSO alloy supports liquid–solid correlation, and hence, the formation criteria of the LPSO phase in Type I LPSO alloys can be developed based on the common liquid characteristics of Type I LPSO Mg-Y-X alloys as follows: X should result in the reduction in equilibrium volume and cohesive energy; Y should repulse Y and be attracted by both Mg and X, and X should be repulsed by both Mg and X; X should enhance the threefold and fourfold symmetries and weaken the fivefold and sixfold ones so that the local structural symmetries are distributed close to liquid pure Mg.

The outbreak and subsequent recurring waves of COVID −19 pose threats on the emergency management and people’s daily life, while the large-scale spatio-temporal epidemiological data have sure come in handy in epidemic surveillance. Nonetheless, some challenges remain to be addressed in terms of multi-source heterogeneous data fusion, deep mining, and comprehensive applications. The Spatio-Temporal Artificial Intelligence (STAI) technology, which focuses on integrating spatial related time-series data, artificial intelligence models, and digital tools to provide intelligent computing platforms and applications, opens up new opportunities for scientific epidemic control. To this end, we leverage STAI and long-term experience in location-based intelligent services in the work. Specifically, we devise and develop a STAI-driven digital infrastructure, namely, WAYZ Disease Control Intelligent Platform (WDCIP), which consists of a systematic framework for building pipelines from automatic spatio-temporal data collection, processing to AI-based analysis and inference implementation for providing appropriate applications serving various epidemic scenarios. According to the platform implementation logic, our work can be performed and summarized from three aspects: (1) a STAI-driven integrated system; (2) a hybrid GNN-based approach for hierarchical risk assessment (as the core algorithm of WDCIP); and (3) comprehensive applications for social epidemic containment. This work makes a pivotal contribution to facilitating the aggregation and full utilization of spatio-temporal epidemic data from multiple sources, where the real-time human mobility data generated by high-precision mobile positioning plays a vital role in sensing the spread of the epidemic. So far, WDCIP has accumulated more than 200 million users who have been served in life convenience and decision-making during the pandemic.

BackgroundGastroschisis has increased in recent years, however, complicated gastroschisis is associated with higher mortality, as well as higher health care costs and disease burdens from short- and long-term complications.Case introductionA woman aged 25 years old at 37 + 1 weeks gestation (gravida 2; para 0) was admitted to the hospital because of foetal gastroschisis. Targeted quaternary ultrasound performed at our hospital showed that 34 mm of the abdominal wall was interrupted continuously, an intestinal echo with a range of approximately 88 × 50 mm was seen bulging outwards the local area close to the intestinal wall showed a 34 × 23 m anecho, and the foetus was measuring 2 weeks smaller than expected. After MDT including the maternal-foetal medicine, ultrasound, paediatric surgery, neonatal intensive care unit (NICU), and anaesthesiology departments, caesarean section was performed at 37 + 2 weeks. A baby boy was delivered, the small intestine, large intestine and stomach were seen outside of the abdomen, the abdominal cavity was excluded from the defect on the right side of the umbilical cord, the mesentery was shortened, and the intestinal tube had obvious oedema After paediatric surgical discussion, silo bag placement and delayed closure was performed, the placement process was smooth. One week following silo placement, the abdominal contents had been fully reduced below the fascia following daily partial reductions of the viscera,and the second stage of the operation was performed under general anaesthesia. The newborn was successfully discharged from the hospital 20 days after the operation and was followed up, with good growth, normal milk intake and smooth bowel movements.ConclusionsThe diagnosis and treatment of complicated gastroschisis needs to be carried out under multidisciplinary team treatment. Delivery by cesarean section after 37 weeks is feasible.Immediate postpartum surgery is possible, and the choice of surgical modality is determined by the child's condition, emphasizing that it should be performed without adequate sedation under anaesthesia. A standardized postoperative care pathway appropriate to risk should be developed to optimize nutritional support and antibiotic use, and standardized enteral feeding practices should be sought with long-term follow-up.

Background: Some reports have indicated a high expression level of ASB3 in various cancers, but its role in hepatocellular carcinoma (HCC) remains elusive. Methods: ASB3 levels and clinical features were obtained from the TCGA database. Meanwhile, the expression levels of ASB3 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Imunohistochemistry (IHC). ASB3-related downstream molecular analysis was carried out with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Pathways linked to ASB3 expression were identified by means of gene set enrichment analysis (GSEA). Single-sample GSEA (ssGSEA) aided in conducting a correlation analysis of ASB3 with immune infiltration. Functional experiments were performed in HepG2 cells by using the small interfering RNA. Results: ASB3 expression was remarkably higher in HCC tissues. Its remarkable precision in forecasting cancer suggests that ASB3 might serve as an unidentified diagnostic and prognostic indicator of HCC. Higher ASB3 expression led to worse overall survival (OS), particularly in various clinical subgroups of HCC. GO/KEGG analysis indicated that critical biological activities, such as the activation of complement systems and humoral immune response, could potentially underlie the progression of HCC. Furthermore, GSEA demonstrated enrichment of certain pathways, including the MAPK, IL17, and fibrinolysis pathways, in samples with elevated ASB3 levels. ASB3 exhibited a substantial association with T helper cells, dendritic cells (DCs), and central memory T (Tcm) cell infiltration level. Cell function experiments confirmed elevated ASB3 levels in HCC cell lines as opposed to hepatic epithelial cell lines. Moreover, the ability of HCC cells to proliferate and invade was remarkably reduced by ASB3 knockdown. Conclusion: Summarize briefly, we found that ASB3 can be a promising biomarker in HCC.

BackgroundRibonucleotide reductase regulatory subunit M2 (RRM2) has been reported to be an oncogene in some malignant tumors, such as lung adenocarcinoma, oral squamous cell carcinoma, glioblastoma, and breast cancer. However, the clinical significance of RRM2 in hepatocellular carcinoma has been less studied. The aim of this study was to assess the importance of RRM2 in hepatocellular carcinoma (HCC) based on the Cancer Genome Atlas (TCGA) database.MethodsThe RRM2 expression levels and clinical features were downloaded from the TCGA database. Immunohistochemistry results between tumor tissues and normal tissues were downloaded from the Proteinatlas database. Meanwhile, the expression levels of RRM2 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Western Blotting. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein-interactions (PPI) network were constructed to analyze RRM2-related downstream molecules. In addition, RRM2 expression-related pathways performed by gene set enrichment analysis (GSEA). Association analysis of RRM2 gene expression and immune infiltration was performed by single-sample GSEA (ssGSEA).ResultsThe RRM2 expression level in tumor tissues was higher than normal tissues (P

It is challenging to study how topologically close-packed phases (TCPs) transform between one phase to another. Here the authors use atomic-resolved tools to look at the transformation between μ and P phases, revealing an intrinsic link between seemingly unrelated TCP configurations.

Objectives: The novel coronavirus (COVID-19) epidemic is reaching its final phase in China. The epidemic data are available for a complete assessment of epidemiological parameters in all regions and time periods. Methods: This study aims to present a spatiotemporal epidemic model based on spatially stratified heterogeneity (SSH) to simulate the epidemic spread. A susceptible-exposed/latent-infected-removed (SEIR) model was constructed for each SSH-identified stratum (each administrative city) to estimate the spatiotemporal epidemiological parameters of the outbreak. Results: We estimated that the mean latent and removed periods were 5.40 and 2.13 days, respectively. There was an average of 1.72 latent or infected persons per 10,000 Wuhan travelers to other locations until January 20th, 2020. The space-time basic reproduction number (R0) estimates indicate an initial value between 2 and 3.5 in most cities on this date. The mean period for R0 estimates to decrease to 80%, and 50% of initial values in cities were an average of 14.73 and 19.62 days, respectively. Conclusions: Our model estimates the complete spatiotemporal epidemiological characteristics of the outbreak in a space-time domain. These findings will help enhance a comprehensive understanding of the outbreak and inform the strategies of prevention and control in other countries worldwide.

Summary: Facilitating the mass transfer and enlarging the active surface area are two mutually exclusive demands in porous materials, while structural hierarchy could settle this issue by constructing continuous channels with different length scales. However, it is a great challenge to fabricate porous metallic materials with three or more geometrically similar hierarchy levels. Herein, a novel strategy combining vapor phase dealloying with electrochemical dealloying is proposed to achieve nanoporous gold (NPG) with three-level nested hierarchy (N3PG), in which the length scale covers micron (5866.8 ± 1445.5 nm), submicron (509.9 ± 106.0 nm), and nanometer (20.1 ± 3.0 nm) for each level. Notably, the structural superiority of such material is manifested by its faster charge transfer behaviors, as benchmarked with unimodal and bimodal NPG (N1PG and N2PG). The present strategy is of great potential to fabricate other hierarchically porous metals with enhanced functional and structural properties.

Abstract Background To investigate the readiness for hospital discharge of patients discharged with tubes from the department of hepatobiliary surgery and to explore the influencing factors. Methods A cross-sectional survey was conducted for the 161 patients with tubes who were discharged from the department of hepatobiliary surgery of Shaoxing Second Hospital by using the modified Chinese version of Readiness for Hospital Discharge Scale (RHDS) and Quality of Discharge Teaching Scale (QDTS). General data of the patients, such as gender, age, BMI (body mass index), and educational level, were collected. Results According to the statistical results, the total score of the RHDS was 142.40 ± 23.98, and that of the QDTS was 148.14 ± 17.74. Multiple linear step-wise regression analysis revealed that the total score of the QDTS, residence and educational level were the independent influencing factors of the readiness for hospital discharge (p

The crystallization processes of titanates are central to the fabrication of optical and electrical crystals and glasses, but their rich polymorphism is not fully understood. Here, authors identify when and how polymorphic selection takes place during the crystallization of an undercooled barium titanate melt using aerodynamic levitation, in situ time resolved high energy X-ray diffraction and ab initio molecular dynamics simulations.

To analyze the diagnostic value of CD40 ligand (CD40L), soluble growth stimulating expression gene 2 protein (ST2), interleukin-6 (IL-6), and C-reactive protein (CRP) are used in patients with acute coronary syndrome (ACS). Serum samples were collected from 259 ACS patients admitted to our hospital. Additionally, 119 healthy individuals who received physical examination in the hospital at the same time period were included as normal control. The levels of CD40L, ST2, IL-6, and CRP in 259 patients with ACS and 119 healthy subjects were detected by ELISA. The levels of CD40L, ST2, IL-6, and CRP were significantly increased in unstable angina (UA) patients, while ST2, CRP, and IL-6 were significantly elevated in acute myocardial infarction (AMI) patients. Pearson correlation analysis showed that ST2 was also closely related to CRP in ACS patients, while ST2 was positively correlated with creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and troponin I (cTnI) in AMI patients. The levels of glucose (GLU) and low-density lipoprotein cholesterol (LDL-c) were significantly decreased, while the levels of high-density lipoprotein cholesterol (HDL-c) were significantly increased in AMI patients treated with stent implantation. Furthermore, the level of serum CD40 L was significantly elevated in coronary heart disease (CHD) patients treated with stent implantation, while the levels of ST2 and IL-6 in AMI patients treated with the stent implantation decreased significantly. The levels of inflammatory factors significantly changed in patients with ACS. These inflammatory factors may involve in the pathological progression of ACS and can be used as diagnostic indexes for ACS.

Objectives: The outbreak of atypical pneumonia caused by the novel coronavirus (COVID-19) has currently become a global concern. The generations of the epidemic spread are not well known, yet these are critical parameters to facilitate an understanding of the epidemic. A seafood wholesale market and Wuhan city, China, were recognized as the primary and secondary epidemic sources. Human movements nationwide from the two epidemic sources revealed the characteristics of the first-generation and second-generation spreads of the COVID-19 epidemic, as well as the potential third-generation spread. Methods: We used spatiotemporal data of COVID-19 cases in mainland China and two categories of location-based service (LBS) data of mobile devices from the primary and secondary epidemic sources to calculate Pearson correlation coefficient,r, and spatial stratified heterogeneity, q, statistics. Results: Two categories of device trajectories had generally significant correlations and determinant powers of the epidemic spread. Bothr and q statistics decreased with distance from the epidemic sources and their associations changed with time. At the beginning of the epidemic, the mixed first-generation and second-generation spreads appeared in most cities with confirmed cases. They strongly interacted to enhance the epidemic in Hubei province and the trend was also significant in the provinces adjacent to Hubei. The third-generation spread started in Wuhan from January 17–20, 2020, and in Hubei from January 23–24. No obvious third-generation spread was detected outside Hubei. Conclusions: The findings provide important foundations to quantify the effect of human movement on epidemic spread and inform ongoing control strategies. The spatiotemporal association between the epidemic spread and human movements from the primary and secondary epidemic sources indicates a transfer from second to third generations of the infection. Urgent control measures include preventing the potential third-generation spread in mainland China, eliminating it in Hubei, and reducing the interaction influence of first-generation and second-generation spreads.

In order to promote the resin modifying agent applied into pavement materials, a type of resin modifying agent was selected as the modifier to prepare modified asphalt. The molecular crystal structure of the modifying material was characterized by using the X-ray diffraction test (XRD). The microstructure and element composition of PA6 was investigated through focused ion beam scanning electron microscopy (FIB-SEM). The thermal property and functional groups of PA6 were studied by thermogravimetric analysis-Fourier infrared spectroscopy (TG-FTIR) test. The physical property and rheological properties of PA modified asphalt were evaluated to confirm the applying feasibility of PA6 in asphalt. The results indicated that PA6 was the semicrystalline polymer and the existence of γ crystal form might improve the toughness of asphalt materials effectively. The thermal decomposition process of PA6 could be divided into three stages roughly: inert weight loss stage, rapid weight loss stage, and stable stage. The amount of PA6 modifier should be appropriately controlled during the application process to ensure the comprehensive effect of PA6 on high-temperature performance and low-temperature performance. The corresponding initial modulus attenuation value of PA modified asphalt was less than 70# asphalt under the same test conditions.

Microsurfacing is a standard preventive maintenance technology developed on the basis of slurry sealing technology. However, the high temperature and rainy season in Guangdong Province affect its expanded application because of its low water resistance and short service life. So, high-performance microsurfacing, a new microsurfacing technology, has been developed. The key to this technique is an appropriate proportion of water-based epoxy resin and waterborne epoxy curing agent, which could generate a chemical reaction to form a high-performance bonding network structure of space. And indoor wet-wheel wear test shows that its antiwear ability and resistance to water damage are evidently increased (to over 50%) compared with the conventional microsurfacing. Furthermore, from the long-term road performance results, the antisliding and water resistance performance of high-performance microsurfacing is much higher than the conventional technique.

In the present work, a new model of the atomic cluster structure, which is determined by metal Wulff construction with the crystal structure inside, is proposed to describe the structures of metallic melts. The shapes of the structures are determined by surface energies of different crystal plane groups, calculated from density functional theory (DFT), while the size is given by the pair distribution function (PDF) of the experimental high-temperature X-ray diffraction (HTXRD). Taking Aluminum (Al) and Copper (Cu) as the representative examples, we demonstrate that the simulated XRD curves from present models match the experimental results quite well, not only regarding the position and width of the peaks but also the relative intensity of the first and second peaks. These results indicate a successful model to describe the properties of metallic melts. The model also explains a main peak deviation phenomenon between the XRD of metallic melt and the solid ones in pure metal Al. Finally, a physical picture of metallic melt is given, which is mainly composed of atomic cluster structures and free atoms around them.

An integrated technique consisting of oxidation and coagulation–flocculation processes was investigated in order to provide an effective method for the treatment of biologically pre-treated leachate and to reduce pollutants to values under the limit required for discharging to the receiving waters. Leachate containing 985 mg L−1 chemical oxygen demand (COD) was treated by using oxidation with NaClO, coagulation/flocculation with aluminium sulfate (alum) or poly-ferric sulfate (PFS) as well as combined pre-oxidation followed by coagulation/flocculation. Oxidation resulted in the removal of COD and colour up to 78.9 and 88.4%, respectively, however residual COD values were over 200 mg L−1 even under intensive experimental conditions (high dosage of NaClO and prolonged oxidation time). Coagulation with PFS was found to be more efficient in comparison with alum, and it yielded a residual COD of 184 mg L−1 the optimum coagulation conditions (polyacrylamide (PAM) 5 mg L−1, PFS 30 mg L−1, pH 6, reaction time 20 min). The combined process involving oxidation followed by coagulation/flocculation with PFS resulted in residual COD values lower than 100 mg L−1 the following conditions: 40–60 min pre-oxidation with 30 mg L−1 NaClO followed by coagulation with 200–250 mg L−1. Hence, pre-oxidation with NaClO followed by coagulation with PFS was recommended for removal of biologically-treated substances from the biologically-treated or stabilized leachate. [ABSTRACT FROM PUBLISHER]

Xiao-Er-An-Shen Decoction (XEASD) has been used clinically for the treatment of Tourette syndrome (TS) in children for more than 20 years in mainland China. The biochemical mechanism underlying the therapeutic action produced by XEASD treatment against TS remains unknown. However, a previous study has shown that pre-incubation of PC12 neuronal cells with XEASD can induce neurite outgrowth and protect against oxidative stress. In the present study, using a mouse model of TS induced by 3,3’-iminodipropionitrile (IDPN), stereotypy scoring, and locomotor activity were assessed. Levels of neurotransmitters including glutamate, aspartate, and gamma-aminobutyric acid (GABA) in brain tissue as well as plasma cyclic adenosine monophosphate (cAMP) were measured using assay kits. The ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) and Mn-superoxide dismutase (MnSOD) activity in brain mitochondrial fractions as well as mitochondrial glutathione reductase and cytosolic γ-glutamylcysteine activities were also examined. The phosphorylation of cAMP-responsive element binding protein (CREB) in brain tissue was measured by Western blot analysis. XEASD treatment was found to significantly ameliorate the severity of behavioral symptoms in affected mice, as evidenced by decreases in the stereotypy score and locomotor activity. The beneficial effect of XEASD was accompanied by the reversal of abnormal levels of GABA, glutamate, and aspartate, in brain tissue of IDPN-challenged mice. In addition, XEASD treatment increased plasma cyclic adenosine monophosphate (cAMP) levels and activated the phosphorylation of CREB in brain tissue of TS mice. Furthermore, XEASD treatment was found to enhance the antioxidant status of brain tissue in affected mice, as evidenced by increases in the GSH/GSSG ratio and the activity of MnSOD in brain mitochondrial fractions. Taken together, these experimental results will hopefully provide insight into the pharmacological basis for the beneficial effects of XEASD in children suffering from TS.

Through first-principles molecular dynamics simulation, the self-diffusion coefficients of five elements in the four liquid binary M-Si (M=Al,Fe,Mg,Au) alloy systems are obtained under the same overheating temperature. Except for DFe, the self-diffusion coefficient of the other four elements vary significantly with concentration of Si (cSi). The mixing enthalpy between Si and M elements determines the slop of DSi vs cSi curves in Si-rich range. The dominant factor on DSi is the partial coordination number of NSiSi: the larger the NSiSi is, the smaller DSi becomes. The secondary factor on DSi is the medium-range order in liquid alloys: the stronger the medium-range order is, the smaller DSi will be. Complex behavior of coupling or decoupling of self-diffusion coefficients in these liquid binary alloys are observed.

Kinesin-1 is a typical motile molecular motor and the founding member of the kinesin family. The most significant feature in the unidirectional motion of kinesin-1 is its processivity. To realize the fast and processive movement on the microtubule lattice, kinesin-1 efficiently transforms the chemical energy of nucleotide binding and hydrolysis to the energy of mechanical movement. The chemical and mechanical cycle of kinesin-1 are coupled to avoid futile nucleotide hydrolysis. In this paper, the research on the mechanical pathway of energy transition and the regulating mechanism of the mechanochemical cycle of kinesin-1 is reviewed.

Functional connectivity MRI (fcMRI) has become instrumental in facilitating research of human brain network organization in terms of coincident interactions between positive and negative synchronizations of large-scale neuronal systems. Although there is a common agreement concerning the interpretation of positive couplings between brain areas, a major debate has been made in disentangling the nature of negative connectivity patterns in terms of its emergence in several methodological approaches and its significance/meaning in specific neuropsychiatric diseases. It is still not clear what information the functional negative correlations or connectivity provides or how they relate to the positive connectivity. Through implementing stepwise functional connectivity (SFC) analysis and studying the causality of functional topological patterns, this study aims to shed light on the relationship between positive and negative connectivity in the human brain functional connectome. We found that the strength of negative correlations between voxel-pairs relates to their positive connectivity path-length. More importantly, our study describes how the spatio-temporal patterns of positive connectivity explain the evolving changes of negative connectivity over time, but not the other way around. This finding suggests that positive and negative connectivity do not display equivalent forces but shows that the positive connectivity has a dominant role in the overall human brain functional connectome. This phenomenon provides novel insights about the nature of positive and negative correlations in fcMRI and will potentially help new developments for neuroimaging biomarkers.

In this paper, the relationship between the liquid structure and the corresponding solidified microstructure of an Al-Si-Mg-P alloy was studied. Experimental results show that Mg can reduce the phosphorous-modification effect if it was added after adding Al-P alloy. However, when it is added before adding Al-P alloy, Mg has no effect on the phosphorous-modification. It is considered that the difference in liquid structure induced by changing the adding order of Mg should be responsible for the above phenomenon, and was investigated by ab initio molecular dynamics simulation (AIMD). It was believed that the high-active Mg atoms could bond P atoms to form P-Mg clusters and then reduce the modification effect of AlP, when pure Mg was added into the prepared Al-Si-P melt. When the pure Mg was added into Al-Si melt before adding Al-P alloy, the Mg atoms would be first occupied by Si atoms to form Mg-Si clusters, and thus lose the ability to eliminate P-Al clusters which dissolve into melt later, leading to a good phosphorous-modification effect.