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Abstract Background Bone morphogenetic protein 9 (BMP9) has been shown to regulate processes such as angiogenesis, endothelial dysfunction, and tumorigenesis. However, the role of BMP9 in preeclampsia (PE) is unclear. The purpose of this study was to investigate the role and mechanism of BMP9 in PE. Methods The effects of BMP9 on the viability, migration and invasion of HTR-8/Svneo cells were investigated by CCK-8 assay, wound healing assay and Transwell invasion assay. The effect of BMP9 on apoptosis of HTR-8/Svneo cells was detected by flow cytometry. Plasma levels of BMP9, SDF1 and CXCR4 were detected by ELISA kit. qRT-PCR and Western blot were used to detect the expression levels of each gene in the cells. Results Overexpression of BMP9 promoted the proliferation and migration of trophoblast cells and inhibited apoptosis. Knockdown of BMP9 had the opposite effect. The levels of BMP9, SDF1 and CXCR4 in the plasma of PE patients were down-regulated, and BMP9 was positively correlated with the levels of SDF1 and CXCR4. BMP9 also significantly upregulated the mRNA and protein levels of SDF1 and CXCR4 in HTR-8/SVneo cells. Further mechanistic studies found that BMP9 promoted the migration and invasion of HTR-8/SVneo cells and inhibited apoptosis by activating the SDF1/CXCR4 pathway. Conclusion We demonstrate for the first time that BMP9 promoted the migration and invasion of HTR-8/SVneo cells and inhibits apoptosis by activating the SDF1/CXCR4 pathway. This suggests that BMP9 may be a biomarker molecule for PE.

Since 2010, the cases and incidences of human brucellosis have been increasing annually in Qinghai (QH) Province. Molecular epidemiology and phylogenetic analyses of strains from this region are crucial to better understand the transmission of the disease and the evolutionary patterns of Brucella strains. In this study, classical bio-typing assay, multilocus variable-number tandem repeat analysis, and the whole-genome sequencing–single-nucleotide polymorphism approach were used to illustrate the epidemiological and evolutionary patterns of Brucella melitensis. A total of 54 B. melitensis bv. 3 strains were isolated and molecularly characterized, with all strains belonging to the East Mediterranean lineages. Cross-regional transmission events (i.e., between counties) were caused by common sources of infection, suggesting that predominant circulating genotypes are endemic in different regions. Strengthening surveillance in animal brucellosis and controlling infected animals’ cross-border movement are necessary. Two strains isolated from humans and marmots were clustered in the same sub-clade, implying the possible existence of direct and/or indirect contact between sheep (and goats) and wildlife (marmots), but this needs to be verified by further investigations. The global-scale phylogenetic analysis indicated that 54 strains sorted into six subclades, four of which formed independent lineages, suggesting that the increase in the incidence rate of human brucellosis may be caused by local circulating lineages. Further strengthening the serology and pathogen surveillance of animals (wildlife) and humans will contribute to an in-depth understanding of the transmission chain of human brucellosis in this region.

Purpose: Online integrated marketing is arousing extensive attention from industry and academia, whereas no uniform conclusion on the effectiveness of integrated versus single marketing has been reached thus far. Accordingly, the integrated marketing effectiveness of paid search advertising and social advertising, and the moderating role of product type in it are primarily investigated in this study. Design/methodology/approach: The interaction between paid search advertising and social advertising and purchase is elucidated. Moreover, the moderating effects of product type on the relationship are examined. The hypotheses are tested using an empirical model in accordance with the natural transaction data from Taobao. Findings/results: An empirical analysis confirms a complementary relationship between paid search and social advertising on enhancing purchase. Furthermore, this study suggests that paid search advertising is more probably employed for the purchase of hedonic products, and social advertising more markedly affects the sales of utilitarian products. Moreover, the above-described two advertisements jointly increase the sales of hedonic products. Practical implications: The results provide applicable guidance for sellers’ advertising strategies on online shopping platforms. Sellers should stimulate sales by strategically using integrated marketing tools, and they should adopt different marketing strategies in accordance with different product types. Originality/value: The findings reveal the complementary relationship between paid search and social advertising. Furthermore, this study expands the application of dual-process theory and analyses the information processing of utilitarian and hedonic products.

GeTe and Ge0.99-xIn0.01SnxTe0.94Se0.06 (x = 0, 0.01, 0.03, and 0.06) samples were prepared by vacuum synthesis combined with spark plasma sintering (SPS). The thermoelectric properties of GeTe were coordinated by multiple doping of Sn, In, and Se. In this work, a maximum zT(zT = S2σT/κ) of 0.9 and a power factor (PF = S2σ) of 3.87 μWmm−1 K−2 were obtained in a sample of Ge0.99In0.01Te0.94Se0.06 at 723K. The XRD results at room temperature show that all samples are rhombohedral phase structures. There is a peak (~27°) of the Ge element in GeTe and the sample (x = 0), but it disappears after Sn doping, indicating that Sn doping can promote the dissolution of Ge. The scattering mechanism of the doped samples was calculated by the conductivity ratio method. The results show that phonon scattering Is dominant in all samples, and alloy scattering is enhanced with the increase in the Sn doping amount. In doping can introduce resonance energy levels and increase the Seebeck coefficient, and Se doping can introduce point defects to suppress phonon transmission and reduce lattice thermal conductivity. Therefore, the thermoelectric properties of samples with x = 0 improved. Although Sn doping will promote the dissolution of Ge precipitation, the phase transition of the samples near 580 K deteriorates the thermoelectric properties. The thermoelectric properties of Sn-doped samples improved only at room temperature to ~580 K compared with pure GeTe. The synergistic effect of multi-element doping is a comprehensive reflection of the interaction between elements rather than the sum of all the effects of single-element doping.

Human rotavirus (HRV) is an enteric virus that causes infantile diarrhea. However, the risk factors contributing to HRV colonization in young adults have not been thoroughly investigated. Here, we compared the differences in dietary habits and composition of gut microbiota between asymptomatic HRV-infected young adults and their healthy counterparts and investigated potential risk factors contributing to HRV colonization. Our results indicated that asymptomatic HRV-infected adults had an excessive intake of milk and dairy and high levels of veterinary antibiotics (VAs) and preferred veterinary antibiotic (PVAs) residues in urine samples. Their gut microbiota is characterized by abundant Gram-negative (G−) bacteria and high concentrations of lipopolysaccharide (LPS). Several opportunistic pathogens provide discriminatory power to asymptomatic, HRV-infected adults. Finally, we observed an association between HRV colonization and disrupted gut microbiota caused by the exposure to VAs and PVAs. Our study reveals the traits of disrupted gut microbiota in asymptomatic HRV-infected adults and provides a potential avenue for gut microbiota-based prevention strategies for HRV colonization.

Objective: Rotavirus (RV), one of non-enveloped double-strained RNA viruses, can cause infantile diarrheal illness. It is widely accepted that RV is transmitted mainly via feces-oral route. However, infected asymptomatic adults are becoming the source of infection. It is necessary to explore the underlying mechanism of RV replication in adult's intestine. Methods: After recruiting healthy volunteers and RV asymptomatic carriers, we firstly investigated the association of animal-derived food intake with antibiotic level in urine samples. Secondly, we compared the difference in the structure of gut microbiota, and identified the taxa that most likely explained the difference. Finally, we investigated the impact of lipopolysaccharide (LPS), produced by gram-negative bacteria, on RV replication in vivo and in vitro. Results: We found that 10% of participants were RV asymptomatic carriers in our study. High intake of animal-derived food was positively correlated to antibiotic level in urine samples. The disrupted gut microbiota in RV carriers was characterized by high abundance of antibiotic resistant gram-negative bacteria and high level of LPS. The disrupted gut microbiota caused by penicillin treatment was benefit to RV replication in vivo. LPS enhanced RV thermal stability in vitro. Conclusions: Our findings suggest that the imbalanced gut microbiota caused by antibiotic exposure plays an important role in RV replication, and brings risk to health complications.

Surface functionalization of piezoelectric greatly determines its piezo-catalytic activity and selectivity in that functional group affect specific reactants’ surface adsorption and activation abilities. Herein, we propose chemical functionalization on the surface of nano-scaled BaTiO3 piezoelectric via a one-pot hydrothermal process using polyethylene glycol as surfactant, and evaluate its piezo-catalytic activity and selectivity by degrading model antibiotic and dye reactants under ultrasonic vibrations. Acetate or/and oxalic unidentate ligands on the surface of BaTiO3 nanobelts can be formed by controlling precursor and hydrothermal parameters. Particularly, oxalic acid functionalized BaTiO3 nanobelts presented a high piezo-catalytic rate constant of 0.068 min−1 for Rhodamine B solution and maintained >87% degradation efficiency within 30 min under the condition of ultrasonic bath with 40 kHz and 100 W, which was mainly ascribed to piezo-sensitization effect. This work provides references for the preparation of chemical functionalized catalysts and also contributes to the development of novel catalysts for special applications.

Chimeric antigen receptor (CAR)-T cell therapy is a novel cell therapeutic approach that is increasingly being used to treat patients with relapsed refractory B-cell lymphoma. Despite the efficacy of CAR T cell therapy, it has various adverse effects that can affect any organ in the body. The application of immune checkpoint inhibitors such as programmed death 1 (PD-1), programmed death ligand 1 (PDL-1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies has previously been reported to be associated with immune-related adverse events such as thyroid dysfunction and thyroiditis. Reports of immune-related adverse reactions after CAR T therapy are currently extremely rare, with only one case of a cytokine storm (CRS) combined with severe arthritis in a patient with ALL after treatment. Here, we describe two cases of Hashimoto’s thyroiditis secondary to CAR T therapy. Two patients with relapsed refractory diffuse large B-cell lymphoma developed elevated peroxidase and globulin antibodies secondary to CAR-T cell therapy and developed Hashimoto’s thyroiditis. Complete remission was achieved in two patients at 1 and 3 months after CAR-T cell therapy. The inflammation of the thyroid tissue may be directly or indirectly related to CAR T cell therapy, and the mechanisms needs to be further investigated.

Nitrogen (N) cycling microorganisms mediate soil nitrogen transformation processes, thereby affecting agricultural production and environment quality. However, it is not fully understood how active N-cycling microbial community in soil respond to long-term fertilization, as well as which microorganisms regulate soil nitrogen cycling in agricultural ecosystem. Here, we collected the soils from different depths and seasons at a 29-year fertilization experimental field (organic/chemical fertilizer), and investigated the transcriptions of N-cycling functional genes and their contribution to potential nitrification and denitrification. We found that long-term fertilization exerted significant impacts on the transcript abundances of nitrifiers (AOA amoA, AOB amoA and hao) and denitrifiers (narG and nosZ), which was also notably influenced by season variation. The transcriptions of AOA amoA, hao, and narG genes were lowest in autumn, and AOB amoA and nosZ transcript abundances were highest in autumn. Compared to no fertilization, soil potential nitrification rate (PNR) was reduced in fertilization treatments, while soil potential denitrification rate (PDR) was significantly enhanced in organic combined chemical fertilizer treatment. Both PNR and PDR were highest in 0–20 cm among the tested soil depths. Path model indicated active nitrifiers and denitrifiers had significant impact on soil PNR and PDR, respectively. The transcriptions of AOA amoA and nxr genes were significantly correlated with soil PNR (Pearson correlation, r > 0.174, p 0.234, p

Bone metastases are associated with poor prognosis in patients with breast cancer and limited therapeutic options. Here the authors exploit near-infrared light responsive macrophages for the tumor-selective delivery of oxaliplatin prodrug for chemo-photodynamic therapy of primary and bone metastatic breast cancer.

Recently, the emergent two-dimensional (2D) ferroelectric materials have provided new possibilities for the miniaturization of ferroelectric systems and the integration of novel 2D nano-electronic devices. In addition to the intrinsic ferroelectrics exfoliated from bulk, 2D heterostructures hybridized from electrically non-polarized van der Waals (vdW) materials have also been proven to be a promising platform for the construction of ferroelectricity. Here, we report 30° twisted bilayer–graphene (TBLG) incommensurate moiré superlattice encapsulated by hexagonal boron nitride (h-BN), in which robust hysteretic resistance was detected at the top interface between h-BN and the TBLG from room temperature down to 40 mK. The hysteretic phenomenon can be understood by the extra carrier induced by the interfacial 2D ferroelectric polarization, which is estimated to be around 0.7 pC/m. Our work of interfacial ferroelectric heterostructure achieved by a TBLG/h-BN hybrid system expands the 2D ferroelectric families and opens more possibilities for future coupling the ferroelectricity with rich electronic and optical properties in vdW twistronic devices.

The excellent microstructure and mechanical properties of Al-Cu alloy deposited using the Direct Energy Deposition (DED) process has been shown in previous studies, which is the most likely aluminum alloy material to meet the load-bearing requirements of hypersonic aircraft. However, its high-temperature performance and the law of microstructure transformation during the high-temperature process still need to be determined. In this paper, DED Al-Cu alloy samples were prepared using the Cold Metal Transfer (CMT) process, CMT Pulse process, and CMT Pulse Advanced process. The effect of different deposition processes on the microstructure and mechanical properties of the deposits was investigated at 200 °C for 30 min. The results show that the Al-Cu alloy’s main strengthening phase θ′ is excessively transformed into the equilibrium θ phase after the high-temperature process, which is the main reason for the degradation in the DED Al-Cu alloy’s properties at high temperatures. Different deposition processes have almost no effect on the high-temperature performance of the DED Al-Cu alloy, and the deposition process can be selected according to the product’s structure.

Al-Cu alloy has broad application prospects in the field of aerospace due to its excellent performance. In this paper, deposits with different Cu contents were prepared by the wire arc additive manufacturing (WAAM) process, and the effects of Cu content on the microstructure and mechanical properties were investigated. The microstructure of Al-Cu alloy was investigated by metallography, scanning electron microscope (SEM), energy-dispersive spectrometer (EDS), and transmission electron microscope (TEM). The results show that both the number and size of the precipitated θ phases (Al2Cu) in the as-deposited material increase with the increase of Cu content. After the T4 treatment, the solid solution amount of Cu in the matrix showed a trend of first increasing and then remaining stable. When the content of Cu was greater than 5.65%, as the Cu content increased, the number and size of the remaining θ phases both increased. In the peak ageing state, the amount of precipitated θ’ phase showed a trend of increasing and then remaining stable. After the T6 treatment, the mechanical properties showed a trend of first increasing and then decreasing with the increase of the content of Cu. When the Cu content was 5.65%, the deposit achieved the best mechanical properties, and the anisotropy of the mechanical properties disappeared. The tensile strength, yield strength, and elongation reached 538 MPa, 478 MPa, and 10.5%, respectively. When the content of Cu was greater than 5.65%, the anisotropy of mechanical properties was obvious, and the fracture mode of the vertical specimen changed from ductile fracture to brittle fracture.

Exposure to veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs) via the food chain is unavoidable for their extensive use not only for treating bacterial infections, but also for use as growth promoters in livestock and aquaculture. One of the consequences is the disturbance of gut microbiota. However, its impact on the virulence and drug resistance of opportunistic pathogens is still unclear. In this study, a total of 26 antibiotics were detected in the urine of 300 young undergraduates in Anhui Province. We found that excessive intake of milk was positively correlated to high levels of VAs and PVAs. It led to the dysbiosis of gut microbiota characterized by high abundance of Bacteroidetes and Proteobacteria. The increase in Proteobacteria was mainly due to a single operational taxonomic unit (OTU) of Escherichia coli (E. coli). We isolated several E. coli strains from participants and compared their drug resistance and virulence using PCR assay and virulence-related assays. We observed that exposure to high levels of VAs and PVAs induced more resistant genes and drove E. coli strain to become more virulent. At last, we conducted transcriptome analysis to investigate the molecular mechanism of virulent and drug-resistant regulators in the highly virulent E. coli strain. We noted that there were multiple pathways involved in the drug resistance and virulence of the highly virulent strain. Our results demonstrated that participants with high-level VAs and PVAs exposure have a disrupted gut microbiota following the appearance of highly drug-resistant and virulent E. coli and, therefore may be at elevated risk for long-term health complications.

Abstract Background Being overweight and obesity during adolescence are worldwide public health problems. This study examined the relationship between actual weight, body image, and emotional and behavioral problems among Chinese adolescents. Methods A total of 3841 adolescents (age range, 11–16 years) from 5 Chinese cities were included in this cross-sectional study. All of the study participants were asked to complete questionnaires (including demographic features, strengths and difficulties questionnaires, pubertal development scale), and their height and weight were measured at the same time. Body image was measured in two ways: self-perceived weight and body satisfaction. The relationship between weight status and mental health was estimated by multivariate logistic regression for boys and girls. Results Our study showed a difference by sex for prevalence of being overweight/obesity and body dissatisfaction among Chinese adolescents. Boys were more likely to be overweight or obese than girls (30.4% vs. 21.5%, p

Cadmium (Cd), widely present in food and drinking water at low doses, can cause health risks. However, the mechanistic effects of long-term Cd exposure at low dose through dietary intake is poorly studied. The aim of this study is to elucidate whether the dysbiosis of gut microbiota caused by Cd at an environmental low dose can aggravate the injury of mice liver, and the possible mechanism is investigated. In order to explore the potential underlying mechanism, the analyses of the variation of gut microbiota composition, intestinal permeability, and hepatic transcriptome were conducted. Our results showed that gut microbiota was disturbed. The rise of intestinal permeability induced by the dysbiosis of gut microbiota resulted in more Cd ions accumulating in mice liver, but it could be restored partly through depleting gut microbiota by antibiotics cocktail. Transcriptomic analyses indicated that 162 genes were significantly differentially expressed including 59 up-regulated and 103 down-regulated in Cd treatment. These genes were involved in several important pathways. Our findings provide a better understanding about the health risks of cadmium in the environment.

Al-Mg alloys can reach medium strength without a solid solution and quenching treatment, thereby avoiding product distortion caused by quenching, which has attracted the attention of wire arc additive manufacturing (WAAM) researchers. However, the mechanical properties of the WAAM Al-Mg alloy deposits obtained so far are poor. Herein, we describe the preparation of Al-Mg-0.3Sc alloy deposits by WAAM and detail the pores, microstructure, and mechanical properties of the alloy produced in this manner. The results showed that the number and sizes of the pores in WAAM Al-Mg-0.3Sc alloy deposits were equivalent to those in Al-Mg alloy deposits without Sc. The rapid cooling characteristics of the WAAM process make the precipitation morphology, size, and distribution of the primary and secondary Al3Sc phases unique and effectively improve the mechanical properties of the deposit. A primary Al3Sc phase less than 3 μm in size was found to precipitate from the WAAM Al-Mg-0.3Sc alloy deposits. The primary Al3Sc phase refines grains, changes the segregated β(Mg2Al3) phase morphology, and ensures that the mechanical properties of horizontal and vertical samples of the deposits are uniform. After heat treatment at 350 °C for 1 h, the WAAM Al-Mg-0.3Sc alloy deposits precipitated a secondary Al3Sc phase, which was spherical (diameter about 20 nm) and had high dispersity. This phase blocks dislocations and subgrain boundaries, causes a noticeable strengthening effect, and further improves the mechanical properties of the deposits, up to a horizontal samples tensile strength of 415 MPa, a yield strength of 279 MPa, and an elongation of 18.5%, a vertical samples tensile strength of 411 MPa, a yield strength of 279 MPa, and an elongation of 14.5%. This Al-Mg-Sc alloy is expected to be widely used in the WAAM field.

In this experiment, Al-Cu-Sn alloy was used as raw material to form deposits with different heat input using the wire-arc additive manufacturing (WAAM) process. The effects of heat input on microstructure and mechanical properties of Al-Cu-Sn alloy deposits were investigated by metallography, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM) and mechanical properties tests. The results show that with increased of heat input, the thickness of the deposits increased and the layer height of the deposits increased. The number and size of pores in the deposits also improved with the increased heat input. The grain size of the deposits in the as-deposited state gradually increased and changed from isometric crystals to columnar crystals, the precipitated θ phases gradually converged on the grain boundary from within the grains. After T6 heat treatment, with increased heat input, the number of unsolved θ phases on the grain boundary increased, and the number of θ phases precipitated out of the matrix decreased as the phase spacing increased. With the increased heat input, the mechanical properties of the deposits gradually decreased, and the fracture mode changed from ductile fracture to brittle fracture.

In this present study, single-wire and double-wire Al−Cu−Sn alloy walls were fabricated by an arc additive manufacturing process. The surface morphology, elemental composition, and microstructure were investigated by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM) techniques. The mechanical properties of both the single-wire and double-wire walls were studied by mechanical property testing. The results showed that the heat input of the double-wire wall was lower than that of the single-wire wall at the same wire feeding speed. The surface microstructure of the double-wire wall showed a more uniform surface than the single-wire wall. The grains of the double-wire wall were found to be isometric crystals in the as-deposited state. The θ phase of the double-wire wall was dispersed with a smaller grain size in the grain boundary. After T6 heat treatment, the θ phase of the double-wire wall was completely dissolved into the aluminum matrix, and a large amount of θ’ enhanced phases were precipitated with a phase spacing of about 15 nm. The mechanical properties of the double-wire wall were shown to have significantly improved performance, which further increased to 490 MPa, 420 MPa, and 12%, respectively. The transverse and longitudinal mechanical properties of the double-wire wall were consistent, and the fracture mode of both was ductile fracture.

Although numerous studies have described the relationship between HPA axis dysregulation and internalizing symptoms among adolescents, research using hair cortisol concentrations in pre- and young adolescent samples has not been reported. We investigated the association of self-reported internalizing symptoms with cortisol concertration in hair among pre- and young adolescents aged 10-12 years. Forty-six boys and 39 girls supplied a hair sample of at least 3 cm in length for an analysis of this period (3 months) cortisol excretion. Saliva cortisol reactivity to the Trier Social Stress Test for Children (TSST-C) also was assessed. The study found a positive association between ratings of depressive symptoms and cumulative levels of hair cortisol only in boys. Furthermore, higher ratings of anxiety symptoms were associated with lower hair cortisol concertration and lower saliva cortisol reactivity among girls. This study provides the first evidence for the notion that depressive symptoms in boys are associated with long-term cortisol concertration in hair, whereas anxiety symptoms in girls are associated with HPA-axis hypoactivity, when hair cortisol concentrations and saliva cortisol reactivity to acute stress are assessed concurrently.