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This paper uses microdata from the 2017 China Time Use Survey (CTUS) to study the impact of leisure patterns on the subjective well-being of the floating population. We find that latent profile analysis (LPA) divides the leisure time allocation patterns of the Chinese floating population into five types: self-entertainment type, family-friendly type, sports fitness type, social-entertainment type and cultural-artistic type. The empirical results show that the sports fitness type and the cultural-artistic leisure type are the most conducive to the improvement of the subjective well-being of the floating population, followed by the social-entertainment type and the family-friendly type, whereas the self-entertainment type does not contribute to the improvement of subjective well-being. The analysis of the mechanism of action shows that social integration is the mediating variable of the leisure patterns promoting the subjective well-being of the floating population. The conclusion has implications for urban managers to better help the floating population in China integrate into the new environment and improve their quality of life. [ABSTRACT FROM AUTHOR]

• Room temperature electrocaloric effect. • Bi 0.5 Na 0.5 TiO 3 -BaTiO 3 -based lead-free ceramics. • Relaxor PVDF-TrFE-CFE terpolymer-based nanocomposites. • PMMA coating on ceramic nanoparticles. • Reducing Joule heat in electrocaloric effect. Recently, electrocaloric effect (ECE)-based cooling technology has attracted a great deal of research attention. With a relatively high energy conversion efficiency (∼70 %) and no generating greenhouse gases, ECE-based cooling technology is suitable for use in the next generation of solid-state cooling devices. In this investigation, the PMMA layer was coated on the surface of (Bi 0.5 Na 0.5)TiO 3 -6BaTiO 3 -1.5 %BiCoO 3 (BNBT-BCO) nanofillers to reduce the Joule heat of BNBT-BCO/terpolymer (P(VDF-TrFE-CFE)) nanocomposite. From the ECE measurement result, the adiabatic temperature change (ΔT) of the BNBT-BCO@P/T-15 nanocomposite film reached 10.33 °C under 90 MV/m, which is 25 % higher than that of the BNBT-BCO/T-15 nanocomposite film (no PMMA coating, ∼8.29 °C) under the same electric field. In addition, the ΔT of the BNBT-BCO@P/T-15 nanocomposite film reached 17.52 °C under 150 MV/m at room temperature. This value is approximately 60 % higher than that of the pristine terpolymer films (ΔT ∼ 10.84 °C) and 17.4 % higher than that of BNBT-BCO@P/T-20 nanocomposite film (ΔT ∼ 14.92 °C). This work creates a new approach to using the surface coating on ceramic nanoparticles to reduce the Joule heat of the nanocomposites and improving the adiabatic temperature change (ΔT) and efficiency of ECE devices. [ABSTRACT FROM AUTHOR]

Real-time quantitative PCR (RT-qPCR) is widely used to measure and evaluate gene expression. The precision and reliability of RT-qPCR are critically dependent on the selection of suitable reference genes (RGs). In this study, an effort was made to identify the optimal RGs for RT-qPCR analysis of adipose and the longissimus dorsi muscle (LM) in buffaloes. RNA sequencing data were firstly analyzed to obtain 10 candidate genes (FKBP1A, C25H16orf72, PNRC2, IQGAP1, ATP5PD, RPL6, NDUFB4, TRA2A, CAPRIN1, and METAP2) that with high and stable expression across adipose tissues. Four other identified RGs (GAPDH, ACTB, TOP2B, and UXT) were selected as well. The expression stability of the candidate RGs was evaluated by three algorithms (geNorm, NormFinder, and BestKeeper) and then further validated by adipocyte and myocyte markers. Our results showed that UXT and TOP2B were the optimal RGs for RT-qPCR analysis across adipose tissues in buffaloes; three RGs, RPL6, UXT, and TOP2B, were the optimal RGs for RT-qPCR analysis across adipose and the LM tissues in buffaloes. This study provides significant information for improving the accuracy of gene expression in research on intramuscular fat deposition in buffaloes. [ABSTRACT FROM AUTHOR]

• We present numerical simulations of dynamic elastoplastic plates by using the non-incremental (BEN) principle. • Unlike the standard incremental procedure, the BEN principle characterizes the entire trajectory. • Two kinds of plates: the Love-Kirchhoff and the Reissner-Mindlin circular plates undergoing uniform pressure are studied. • The analytical results are compared against numerical one derived by the FEM. This paper is devoted to the numerical simulations of elastoplastic plates at small strains by using the non-incremental Brezis-Ekeland-Nayroles (BEN) principle. This space-time variational principle is based on the energy dissipation and transforms the boundary value problem into a null minimization one under constraints. Unlike the standard incremental procedure, the BEN principle characterizes the entire trajectory and delivers the mechanical fields at all time steps simultaneously. Two kinds of plates: the thin plate Love-Kirchhoff and the thick Reissner-Mindlin circular plates undergoing uniform pressure are studied respectively. The description of the dicretization of the principle using the mixed finite element method and the implementation are detailed. The obtained results are compared against analytical solutions provided in the literature and numerical predictions derived by the classical incremental procedure. [ABSTRACT FROM AUTHOR]

In the past few decades, ceramic/polymer nanocomposites have been extensively studied due to their relatively large dielectric constant, high electric energy density, and large charge–discharge efficiency. Antiferroelectric (AFE) materials possess a low remnant polarization (Pr) and relatively high saturation polarization (Ps), which can induce higher storage energy density than relaxor ferroelectric materials. In this investigation, AgNbO3-based AFE ceramic nanoparticles were grafted with a layer of poly(methyl methacrylate) (PMMA) to form AgNbO3–g-PMMA nanoparticles and then the obtained nanoparticles were embedded into a poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) matrix to form an AgNbO3–g-PMMA/PVDF-HFP (AN–g-PMMA/HFP) nanocomposite film. After characterization, it was found that the dielectric constant of the AN–g-PMMA/HFP-5 (5% AgNbO3) nanocomposite film was 12.3, which was 43% higher than that of the pristine PVDF-HFP film. The AN–g-PMMA/HFP-5 nanocomposite film exhibited the largest breakdown field of 500 MV m−1 and the highest energy density of 13 J cm−3, which was increased by 32.5% (from 9.82 to 13 J cm−3), as compared with that of the pristine PVDF-HFP film. The AN–g-PMMA/HFP-5 film exhibited a charge–discharge efficiency of 69.5% at 500 MV m−1, which is 9.5% higher than that of the pristine PVDF-HFP film. This AgNbO3-based nanocomposite film shows great promise for AFE nanocomposite for high energy density capacitor applications. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) has been considered as one of the most common sexually transmitted viruses that may be linked to unexplained infertility in men. The possible mechanisms underlying correlation between HPV infection and infertility could be related to the altered sperm parameters. Current studies have investigated the effect of HPV seminal infection on sperm quality in infertile men, but have shown inconsistent results. Methods: We systematically searched PubMed, Embase, Web of Science and CNKI for studies that examined the association between HPV seminal infection and sperm progressive motility. Data were pooled using a random-effects model. Outcomes were the sperm progressive motility rate. Results are expressed as standardised mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was evaluated by the I-square (I2) statistic. Results: Ten studies were identified, including 616 infertile patients with HPV seminal infection and 2029 infertile controls without HPV seminal infection. Our meta-analysis results indicated that sperm progressive motility was significantly reduced in HPV-infected semen samples compared with non-infected groups [SMD:-0.88, 95% CI:-1.17 ~ − 0.59]. There existed statistical heterogeneity (I2 value: 86%) and the subgroup analysis suggested that study region might be the causes of heterogeneity. Conclusions: HPV semen infection could significantly reduce sperm progressive motility in infertile individuals. There were some limitations in the study such as the differences in age, sample sizes and the number of HPV genotypes detected. Further evidences are needed to better elucidate the relationship between HPV seminal infection and sperm quality. [ABSTRACT FROM AUTHOR]

This paper is concerned with the energy-dissipation Brezis–Ekeland–Nayroles variational principle (BEN principle) for the numerical study of quasi-static elastoplastic and viscoplastic problems in small strains. This principle is based on the dissipation potential and its Fenchel transform and allows to have a consistent view of the whole evolution by computing the nonlinear response along the whole time history as a solution of a suitable minimization problem. In the present work, the BEN principle is applied to address the elastic perfectly plastic and viscoplastic thick hollow cylinder subjected to internal pressure. It turns out that the BEN variational formulation is based on a two-field functional, that leads naturally to discretize the displacement and stress fields. We present the detailing of the discretization and the numerical implementation of the minimization problem by using the mixed finite element method which is more efficient to enforce the yield condition. Computational accuracy and efficiency of the BEN principle is assessed by comparing the numerical results with the analytical ones and the simulations derived by the classical step-by-step finite element procedure. [ABSTRACT FROM AUTHOR]

Recently, due to the advantages of superior compatibility, fewer interface defects, and a high electric breakdown field, all-organic dielectric composites have attracted significant research interest. In this investigation, we produced all-organic P(VDF-TrFE-CFE) terpolymer/PI (terp/PI) composite films by incorporating a small amount of terpolymer into PI substrates for high energy density capacitor applications. The resulting terp/PI-5 (5% terpolymer) composite films exhibit a permittivity of 3.81 at 1 kHz, which is 18.7% greater than that of pristine PI (3.21). Furthermore, the terp/PI-5 film exhibited the highest energy density (9.67 J/cm3) and a relatively high charge–discharge efficiency (84.7%) among the terp/PI composite films. The energy density of the terp/PI-5 film was increased by 59.8% compared to that of the pristine PI film. The TSDC results and band structure analysis revealed the presence of deeper traps in the terp/PI composites, contributing to the suppression of leakage current and improved charge–discharge efficiency. Furthermore, durability tests confirm the stability of the composite films under extended high-temperature exposure and cycling, establishing their viability for practical applications. [ABSTRACT FROM AUTHOR]

• Site-directed mutations of six key residues at the active site of class II photolyase to examine the binding and repair efficiency. • Titration experiment with different concentrations of 8-mer oligomer containing a T<>T dimer to deduce the dissociation constants of class II photolyase. • Quantum yield measurements resulting the higher binding affinity and better repair efficiency than wild type. Photolyase is a flavoprotein that repairs DNA damage caused by solar ultraviolet radiation. The repair quantum yields of the class I photolyases are around 80%, and for the class II photolyases are around 50%. In this research, we designed six key residues at the active site of class II MmPL from Methanosarcina mazei to systematically characterize the binding constants and quantum yields. We used titration experiments to detect the binding affinity of MmPL wild-type and the mutants with the oligomer containing T<>T lesion. Based on the dissociation constants, we can calculate the enzyme-substrate complex concentrations and obtained the repair quantum yields. Through mutation, we unexpectedly obtained higher binding affinity and higher repair quantum yields than the wild type, suggesting the other role of some residues. These results are critical to studies of ultrafast repair dynamics to solve the repair photocycles. [ABSTRACT FROM AUTHOR]

This work examines the feasibility of using a pH-sensitive fluorescent protein as a molecular reporter for enzyme-catalyzed prodrug activation reaction. Specifically, a ratiometric pHluorins was examined for detection of the activity of horseradish peroxidase (HRP) for the activation of indole-3-acetic acid. The pHluorins and HRP were conjugated chemically, forming a biocatalyst with a self-reporting function. Results showed that the characteristic fluorescence intensity ratio of the conjugate shifted from 1.47 to 1.40 corresponding to the progress of the prodrug activation reaction. The effectiveness of applying the conjugate for inhibition of the growth of Bcap-37 cells was also demonstrated simultaneously with reaction monitoring. The results reveal a very promising approach to realizing in situ monitoring of enzyme activities based on pH shifting for enzyme-based prodrug therapy applications. [ABSTRACT FROM AUTHOR]

Lysine acetylation, a ubiquitous and conserved posttranslational modification, has recently been shown to participate in many diverse non-chromatin-associated biological processes in prokaryotes and eukaryotes. However, the full extent and functional significance of acetylation in Schistosoma japonicum is still unknown. To investigate the nature, extent, and biological functions of lysine acetylation in schistosomes, immunoaffinity-based acetyl-lysine peptide enrichment, integrated with mass spectrometry, was used to comprehensively characterize the lysine-acetylated proteins in this parasite. In total, 1109 acetylated proteins and 2393 acetylation sites in S. japonicum were identified, representing the largest acetylome yet reported in a parasite. In a bioinformatic analysis showed that these acetylated proteins were mainly enriched in the biological process categories of metabolism, gene expression, translation, and transport. The classification according to molecular function revealed that the largest class involved the catalytic activity of different enzymes, including oxidoreductase, transferase, and pyrophosphatase activities. Most of the acetylated proteins in the cellular component category occurred in the cytoplasm, membrane, cytoskeleton, and nucleus. These data demonstrate the generality of lysine acetylation and provide the first global survey of acetylation in schistosomes. Our findings are an exciting starting point for the further exploration of the functions of acetylation in the biology of this parasite. Significance Schistosomiasis is one of the world's most prevalent and neglected tropical parasitic zoonotic diseases, and it causes almost 200,000 deaths annually. To control and eradicate schistosomiasis, effective vaccines are urgently required, and drug targets that are essential for schistosome survival must be identified in fundamental studies of schistosome biology. Posttranslational modifications are complex, fundamental, and important mechanisms that regulate the physiological functions of organisms. Lysine acetylation, a ubiquitous and conserved posttranslational modification, has recently been shown to participate in many diverse non-chromatin-associated biological processes in prokaryotes and eukaryotes. However, the full extent and functional significance of acetylation in Schistosoma japonicum is still unknown. To investigate the nature, extent, and biological functions of lysine acetylation in S. japonicum , we employ immunoaffinity-based acetyl-lysine peptide enrichment, integrated with mass spectrometry to comprehensively characterize the lysine-acetylated proteins in this parasite. The results of our data demonstrate the generality of lysine acetylation and provide the first global survey of acetylation in schistosomes. Our findings are an exciting starting point for the further exploration of the functions of acetylation in the biology of this parasite. Meanwhile, identifying the mechanisms and proteins targeted by acetylation may also provide a promising avenue for specific drug design and the development of sophisticated therapeutic strategies. [ABSTRACT FROM AUTHOR]

Schistosomiasis remains a serious public health problem with 200 million people infected and 779 million people at risk worldwide. The schistosomulum and adult worm are two stages of the complex lifecycle of Schistosoma japonicum and excretory/secretory proteins (ESPs) play a major role in host–parasite interactions. In this study, iTRAQ-coupled LC–MS/MS was used to investigate the proteome of ESPs obtained from schistosomula and adult worms of S. japonicum , and 298 differential ESPs were identified. Bioinformatics analysis of differential ESPs in the two developmental stages showed that 161 ESPs upregulated in schistosomula were associated with stress responses, carbohydrate metabolism and protein degradation, whereas ESPs upregulated in adult worms were mainly related to immunoregulation and purine metabolism. Recombinant heat shock protein 70 (HSP70) and thioredoxin peroxidase (TPx), two differential proteins identified in this study, were expressed. Further studies showed that rSjHSP70 and rSjTPx stimulated macrophages expressing high levels of the anti-inflammatory factors TGF-β, IL-10 and Arg-1, and suppressed the expression of the pro-inflammatory cytokines TNF-α, IL-1β, IL-6 and iNOS in LPS-induced macrophages. This study provides new insights into the survival and development of schistosomes in the final host and helps identify vaccine candidates or new diagnostic reagents for schistosomiasis. [ABSTRACT FROM AUTHOR]

Schistosomiasis remains a serious public health problem, with 200 million people infected and 779 million people at risk worldwide. The schistosomulum is the early stage of the complex lifecycle of Schistosoma japonicum in their vertebrate hosts, and is the main target of vaccine-induced protective immunity. Excretory/secretory (ES) proteins play a major role in host–parasite interactions and ES protein compositions of schistosomula of S. japonicum have not been characterized to date. In the present study, the proteome of ES proteins from 14 day schistosomula of S. japonicum was analyzed by liquid chromatography/tandem mass spectrometry and 713 unique proteins were finally identified. Gene ontology and pathway analysis revealed that identified proteins were mainly involved in carbohydrate metabolism, degradation, response to stimulus, oxidation–reduction, biological regulation and binding. Flow cytometry analysis demonstrated that thioredoxin peroxidase identified in this study had the effect on inhibiting MHCII and CD86 expression on LPS-activated macrophages. The present study provides insight into the growth and development of the schistosome in the final host and valuable information for screening vaccine candidates for schistosomiasis. [ABSTRACT FROM AUTHOR]

A paper-based colorimetric biosensor suitable for point-of-care bioassay of blood samples is developed using highly stable enzyme thin-film coatings confined within inkjet printed polymeric microwells. The microwells are developed through a simple one-step inkjet printing of hydrophobic polystyrene on paper, with walls formed by the polymer that fills the gaps inside the paper body. The microwells can also be patterned to be interlinked with printed microchannels for multiplex bioassays. Thin film enzyme coatings confined within the microwells are then constructed, thereby constituting biosensors that work like traditional microwell plates, yet allow easy colorimetric readouts with naked eyes or portable devices, such as smart phones. The efficiency of the paper-based sensor was demonstrated for colorimetric assays of glucose and lactate, both as individual analytes or mixed, as well as samples with red blood cells. Such sensors showed good sensitivities within the concentration ranges of the analytes in human blood (0.5–10 mM), with a visible sensitivity of ＜0.5 mM detectable by naked eyes for a sample size as small as 1 μL. More accurate digital readouts were shown to be feasible with computerized scanners or smartphones. The thin-film coating format affords the paper biosensors an extended lifetime, and they could retain 100% performance over 6 months of storage at room temperature, or up to one month heated at 50 °C, which promises refrigeration-free storage of the sensor. The simple preparation, high enzyme stability and ease-of-use of the paper-based sensor promise low-cost and reliable point-of-care multiplex bioassay for biomedical diagnostics. [ABSTRACT FROM AUTHOR]

The excretory/secretory (ES) proteins of schistosomes play important roles in modulating host immune systems and are regarded as potential vaccine candidates and drug targets. Protein disulfide isomerase (PDI) is an essential enzyme that is involved in disulfide bond formation and rearrangement. In the present study, SjPDI, a 52.8 kDa protein previously identified in a proteomics analysis as one of the ES proteins of Schistosoma japonicum , was cloned and characterized. Western blot analysis showed that recombinant SjPDI (rSjPDI) was recognized by serum from rabbits vaccinated with schistosome worm antigen. Worm protein extracts and ES protein extracts from S. japonicum could react with anti-rSjPDI mouse serum. Real-time PCR analysis indicated that SjPDI was expressed at all developmental stages tested, and a high expression level was detected in 42-day-old male worms. Immunofluorescence analysis revealed that SjPDI was mainly distributed on the tegument and parenchyma of S. japonicum worms. An enzyme-linked immunosorbent assay (ELISA) demonstrated that rSjPDI could induce a high level of rSjPDI-specific IgG antibodies. The biological activity of purified rSjPDI was confirmed by isomerization and antioxidative activity assays. The 35.32%, 26.19% reduction in the worm burden and 33.17%, 31.7% lower liver egg count were obtained in mice vaccinated with rSjPDI compared with the blank control group in two independent trials. Our preliminary results suggest that rSjPDI plays an important role in the development of the schistosome and is a potential vaccine candidate for schistosomiasis. [ABSTRACT FROM AUTHOR]

Abstract: Di-ionizable calix[4]arene-1,3-crown-4 compounds locked in 1,3-alternate, cone, and partial-cone conformations are synthesized for evaluation in metal ion separations. The ionizable functions include carboxylic acid and N-(X)sulfonyl carboxamide groups in which the acidity is tuned by variation of the electron-withdrawing ability of X. Similar synthetic routes were employed for preparation of the cone and 1,3-alternate ligand series. A different preparative route utilizing protection and deprotection was required to obtain the partial-cone analogues. Ligand conformations were confirmed by their proton and/or carbon NMR spectra. X-ray diffraction verified an unusual 1,2-alternate conformation in the solid-state for one synthetic intermediate. Effects of ligand conformation and ionizable group variations on competitive solvent extractions of alkali and alkaline earth metal cations from aqueous solutions into chloroform were assessed. Single species solvent extractions of Hg2+ and Pb2+ were also performed. [Copyright &y& Elsevier]

Abstract: The fish pathogen Vibrio alginolyticus virulence factors and regulation mechanism are barely known except the quorum sensing regulated extracellular products. In the present study, the cleavable isotope-coded affinity tags (cICATs) were used to analyze the differentially expressed extracellular proteins of V. alginolyticus wild-type and a ΔluxO mutant, and a putative peptidase Pep was identified. Quantitative real-time reverse transcription PCR confirmed that the transcription of pep was down-regulated by LuxO. Furthermore, western blotting demonstrated that the expression of Pep was cell-density dependent and quorum sensing regulated in V. alginolyticus. The pep in-frame mutant abolished the swimming and swarming motility, suggesting that it was involved in motility regulation in V. alginolyticus. In liquid medium, the polar flagellum was observed intact in ∆pep mutant while the chemotaxis related gene cheY, which is a response regulator causing change in direction of flagellar rotation, was down-regulated in ∆pep mutant. When ∆pep mutant was grown on hard agar plate, the lateral flagella disappeared and the transcriptions of flagellar biogenesis genes flaK, fliS, lafK, and lafA were down-regulated in ∆pep mutant. These results suggested that Pep was a luxO-regulated extracellular protein and involved in the motility of V. alginolyticus. [Copyright &y& Elsevier]

Abstract: A series of calix[4]arene-dithiacrown-5 and -dithiacrown-6 compounds in cone and 1,3-alternate conformations has been synthesized. Responses of these ionophores to Hg2+ and competing metal ions were determined in solvent polymeric membrane electrodes. High potentiometric selectivity for Hg2+ over Na+ and a variety of transition and heavy metal ions was obtained. [Copyright &y& Elsevier]

The goal of the present work is the demonstration of the ability of the Symplectic Brezis–Ekeland–Nayroles (SBEN) principle for the numerical simulation of dynamic elastoplastic problems in small strains. This non-incremental approach is an alternative method to conventional step-by-step techniques, as it allows the computation of the whole evolution curve over the entire loading history. We show that the SBEN variational formulation yields to a constrained time–space minimization problem. The cost function depends on stress, displacements, and plastic multiplier fields, which, naturally, leads to a mixed finite element discretization. The details of the solution algorithm are illustrated through the numerical study of the elastoplastic response of the thin and thick pressurized tubes, including inertia effects. Moreover, the balance of momentum is handled using two approaches. Firstly, the Schaefer superposition technique is considered, where the balance of momentum is exactly satisfied. Secondly, the balance of momentum is considered as an optimization constraint and satisfied only at the Gauss integration point level of the finite element problem. The accuracy and efficiency of the SBEN principle are assessed by comparing the numerical results with the analytical solutions (for the thin tube) and the predictions derived by the conventional incremental finite element procedure. • A non-incremental Symplectic Brezis–Ekeland–Nayroles (SBEN) principle is presented. • The new approach allows for a space-time formulation of elastoplastic structural response. • Numerical examples investigating the responses of pressurized tubes are presented. • The numerical results are compared with analytical and incremental solutions. [ABSTRACT FROM AUTHOR]

The growing demand for electronic devices has induced a significant requirement for high energy density capacitors. In this investigation, we introduced small groups of cyanoethyl cellulose (CEC) into a polyimide (PI) substrate to create all organic CEC/PI composite films for high energy density capacitor applications. Due to the large dipole moment in C–CN dipoles in CEC groups, the dielectric constant of the CEC/PI-5 (5% CEC) composite increased by 26.3% to 4.31. Compared to the pristine PI film at room temperature, the breakdown field of the CEC/PI-0.5 increased by 4.7% from 502.29 to 526.1 MV m−1 and the energy storage density increased by 95% to 11.70 J cm−3. Furthermore, the CEC/PI-0.5 film exhibited an energy density of 6.39 J cm−3 with the breakdown field of 400 MV m−1 at 150 °C, which is 93.05% higher in energy densities than that of the pristine PI film. Furthermore, simulation results indicate that CEC groups can introduce deep traps in the CEC/PI composite, which can inhibit charge movement in the composite and increase the breakdown field of it. In this study, it was found that by adding small amount of CEC polar group in PI film, the high temperature energy density of CEC/PI composite materials was significantly improved. This study not only makes a significant contribution to the development of high-temperature energy-density capacitors, but also pave a way by using small molecule polar polymers to improve the energy density of dielectric materials at high temperature. [ABSTRACT FROM AUTHOR]

Lead-free ceramics have attracted considerable research attention owing to their environmentally friendly properties as well as their relatively good piezoelectric properties. Herein, we doped BiCoO 3 (BCO) onto (Bi 0.5 Na 0.5)TiO 3 –6BaTiO 3 (BNT-6BT) solid solution at various concentrations and investigated their dielectric and piezoelectric properties. After comparing the Rietveld refinement data with X-ray diffraction (XRD) results, it was found that all the BNT-6BT- x BCO ceramics (x = 0, 0.5%, 1%, and 1.5%) showed the morphotropic phase boundary conformation with coexisting tetragonal (P4bm) and cubic (Pm 3 (＿) m) phases. XRD refinement data also demonstrated that with increasing BCO concentration to 1.5%, the mole ratio between the tetragonal and cubic phases was close to 1:1, which enhanced the piezoelectric performance of the ceramic composites. At a BCO concentration of 1.5%, the strain and piezoelectric coefficient (d 33) of the sample reached 0.31% and 196 pC/N, respectively. The highest effective d 33 * of 489 pm/V was obtained at 110 °C with BNT-6BT-1.5BCO ceramics. The BNT-6BT-xBCO ceramics show great promise for use in high-temperature actuator applications. [ABSTRACT FROM AUTHOR]

In this contribution, we present a space-time formulation of the Newmark integration scheme for linear damped structures under both harmonic and transient excitations. The incremental set of equations of motion and the Newmark approximations are transformed into their corresponding space-time equivalents. The dynamic system is then represented by one algebraic space-time equation only. This equation is projected into a coupled pair of space-time equations, which is solved via the fixed point algorithm. The solution is iteratively assembled by enrichments, each of which is decomposed by a dyadic product of spatial and temporal enrichment vectors. The evolution of the spatial enrichment vectors is investigated during convergence and interpreted by comparing them to the set of linear modes of vibration. The new method is demonstrated by means of four numerical examples, presenting not only the excellent convergence behavior and the numerical efficiency but also the limits of the proposed approach. [ABSTRACT FROM AUTHOR]

Asthenozoospermia is considered as a common cause of male infertility and characterized by reduced sperm motility. However, the molecular mechanism that impairs sperm motility remains unknown in most cases. In the present review, we briefly reviewed the proteome of spermatozoa and seminal plasma in asthenozoospermia and considered post-translational modifications in spermatozoa of asthenozoospermia. The reduction of sperm motility in asthenozoospermic patients had been attributed to factors, for instance, energy metabolism dysfunction or structural defects in the sperm-tail protein components and the differential proteins potentially involved in sperm motility such as COX6B, ODF, TUBB2B were described. Comparative proteomic analysis open a window to discover the potential pathogenic mechanisms of asthenozoospermia and the biomarkers with clinical significance. [ABSTRACT FROM AUTHOR]

pH-dependent protein adsorption on mesoporous silica nanoparticle (MSN) was examined as a unique means for pH monitoring. Assuming that the degree of protein adsorption determines the distance separating protein molecules, we examined the feasibility of nanoscale pH probes based on fluorescence resonance energy transfer (FRET) between two fluorescent proteins (mTurquoise2 and mNeonGreen, as donor and acceptor, respectively). Since protein adsorption on MSN is pH-sensitive, both fluorescent proteins were modified to make their isoelectric points (pIs) identical, thus achieving comparable adsorption between the proteins and enhancing FRET signals. The adsorption behaviors of such modified fluorescent proteins were examined along with ratiometric FRET signal generation. Results demonstrated that the pH probes could be manipulated to show feasible sensitivity and selectivity for pH changes in hosting solutions, with a good linearity observed in the pH range of 5.5-8.0. In a demonstration test, the pH probes were successfully applied to monitor progress of enzymatic reactions. Such an 'in situ-assembling' pH sensor demonstrates a promising strategy in developing nanoscale fluorescent protein probes. [ABSTRACT FROM AUTHOR]

In this contribution, we present a non‐incremental solution procedure for the efficient treatment of elastoplastic problems. To this end, all time history data are decoupled into space and time, and the solution is obtained using the fixed‐point algorithm. [ABSTRACT FROM AUTHOR]

In this contribution, we present a non‐incremental time integration scheme using the implicit Newmark approximations. The result is one space‐time equation that can be solved using the proper general decomposition ansatz. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding. [ABSTRACT FROM AUTHOR]

Vibrio alginolyticus, an opportunistic pathogen that causes vibriosis in miscellaneous fish species, has brought about serious economic damage to the mariculture industry in South China. The mechanism of virulence regulation in V. alginolyticus is yet not known except a Vibrio harveyi-like quorum sensing (QS) system that is established to manipulate the expression of diverse genes including those encoding virulence determinants. In this study, a new TetR family QS regulator, luxT, was identified and characterized in V. alginolyticus. The transcription of luxT gene was cell density dependent and was positively regulated by LuxU, an established QS component relaying the signal from three paralleled QS regulatory systems in V. harveyi. In addition, luxT positively regulated both luxO at transcriptional level and luxR at post-transcriptional level, which is thoroughly different from the established QS regulation mode in V. harveyi and Vibrio vulnificus. The mutant of luxT deletion produced markedly decreased total extracellular proteases and reduced motility ability compared to the wild type and the complemented strain luxT. The fish infection results indicated that mutation of luxT led to marginal attenuation in the virulence of V. alginolyticus, suggesting that LuxT might play a role in the fine-tuning of the virulence via QS in V. alginolyticus. [ABSTRACT FROM AUTHOR]

In Gram-negative bacteria, the TonB/ExbB/ExbD complex is required to energize the specific high-affinity receptors mediating iron uptake processes. In fish pathogen Vibrio alginolyticus MVP01, which exhibited capacities to scavenge iron sources with various specific iron uptake systems, we identified and characterized two sets of TonB systems. In V. alginolyticus, TonB1 and TonB2 systems were arrayed as TonB1–ExbB1–ExbD1 and ExbB2–ExbD2–TonB2, respectively. The transcription of the TonB systems was regulated by the iron concentration in culture medium. While TonB1 system specifically contributed to the hemin and hemoglobin utilization in V. alginolyticus MVP01, both of the TonB systems showed abilities to support the utilization of iron sources from ferrichrome and vibrioferrin, the endogenous siderophore of V. alginolyticus. In addition, when mutants of the TonB systems were inoculated intraperitoneally into the fish Brachydanio rerio, marked attenuation in virulence of V. alginolyticus was observed, indicating that both of the TonB systems are essential for the virulence of V. alginolyticus. [ABSTRACT FROM AUTHOR]

Thioredoxin peroxidases (TPxs) play an important role in maintaining redox homeostasis and in protecting organisms from the accumulation of toxic reactive oxygen species (ROS). In this study, we isolated the thioredoxin peroxidase-3 gene of Schistosoma japonicum, SjTPx-3. The open reading frame (ORF) of SjTPx-3 was 663 bp encoding 220 amino acids with a molecular weight of 24.99 kDa and an isoelectric point of 6.20. Quantitative real-time reverse transcription-polymerase chain reaction indicated that SjTPx-3 was expressed in all different stages of the parasites, with highest expression in 35-day-old worms. The ORF of SjTPx-3 was subcloned into pET-32a (+) vectors and expressed in Escherichia coli. Recombinant SjTPx-3 (rSjTPx-3) was expressed as a soluble protein with good antigenicity, as demonstrated by western blotting. Immunohistochemical analysis revealed that SjTPx-3 was mainly localized on the tegument of the parasites. Mice vaccinated with rSjTPx-3 had a 37.02% ( P < 0.05) reduction in worm burden and 56.52% ( P < 0.05) reduction in liver egg production compared with control, unvaccinated mice. Enzyme-linked immunosorbent assay analysis demonstrated that rSjTPx-3 could induce high levels of anti-rSjTPx-3-specific IgG, IgG1, and IgG2a antibodies. Characteristic Th1 and Th2 immune response cytokines were detected by flow cytometry and were increased by rSjTPx-3. Taken together, these results suggest that SjTPx-3 is an antioxidant enzyme responsible for protecting S. japonicum from oxidative stress. rSjTPx-3 may represent a potential vaccine candidate and/or new drug target for patients with schistosomiasis. [ABSTRACT FROM AUTHOR]

Schistosomiasis remains a serious public health concern in China. BALB/c mice are susceptible to Schistosoma japonicum infection, whereas the Wistar rats are less susceptible. Apoptosis phenomenon was observed in 42 d adult worms of S. japonicum from both rats and mice at the morphologic, DNA, cellular, and gene levels by transmission electron microscopy (TEM), fluorometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis, fluorescein isothiocyanate-annexin-V/propidium iodide staining flow cytometry (FCM) analysis, and real-time PCR. The results showed that the apoptotic state in worms from two different susceptible hosts was diverse. Several classical hallmarks of apoptosis, including cell shrinkage, chromatin condensation and lunate marginalization, splitting of the nucleoli, nuclear shrinkage and apoptotic body formation were observed by TEM. TUNEL analysis showed that there were much more apoptosis spots in adult worms from rats than those from mice. Statistical analysis revealed that the degree of apoptosis and percentage of necrotic cells in adult worms from Wistar rats were significantly greater ( P < 0.01) than those from BALB/c mice by flow cytometry. A total of 15 apoptosis-associated genes including the major components of an intrinsic cell-death pathway were identified from S. japonicum in this study, suggested that a similar apoptosis pathway might occur in S. japonicum . Real-time PCR analyses revealed that the expression levels of most of the tested apoptosis-associated genes, except CASP7 , were significantly higher or at the similar level in adult worms from Wistar rats, as compared to those from BALB/c mice. The results obtained in this study collectively demonstrated that differential development of adult S. japonicum in less-susceptible rats and susceptible mice was significantly associated with apoptosis in the worm, and provided valuable information to guide further investigations of the mechanisms governing apoptosis and host interactions in schistosome infection. [ABSTRACT FROM AUTHOR]

pH plays a vital role in various cellular activities, and real-time observation of the intracellular pH through a pH indicator is very important for studying many physiological processes. In this paper, we studied the pH response of Trp-Trp dipeptide and its derivatives (NATrpMe, NBTrp and TrpMe) by steady-state and time-resolved fluorescence spectroscopy. Both the fluorescence intensities and lifetimes of Trp-Trp dipeptide as well as TrpMe were functions of pH in the physiological range from 5.5 to 9.0. However, NATrpMe and NBTrp showed no difference. The exposed amino was found to be pivotal for its pH dependence. Moreover, an artificially synthesized tetrapeptide (Trp-Trp-Ala-Ser) confirmed the pH sensitivity of N-terminal Trp-Trp residues. The pH values could be quantitatively determined from the fluorescence intensities and lifetimes of the N-terminal Trp-Trp residue. Thus, the N-terminal Trp-Trp residues may be fused into the polypeptides/proteins to serve as an intrinsic pH indicator in fluorescence spectroscopy and imaging. [ABSTRACT FROM AUTHOR]

Background: The outer-tegument membrane covering the schistosome is believed to maintain via the fusion of membranous vesicles. Fusion of biological membranes is a fundamental process in all eukaryotic cells driven by formation of trans-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes through pairing of vesicle associated v-SNAREs (VAMP) with complementary t-SNAREs on target membranes. The purpose of this study was to characterize Schistosoma japonicum vesicle-associated membrane protein 2 (SjVAMP2) and to investigate its potential as a candidate vaccine against schistosomiasis. Methodology/Principal Findings: The sequence of SjVAMP2 was analyzed, cloned, expressed and characterized. SjVAMP2 is a member of the synaptobrevin superfamily harboring the v-SNARE coiled-coil homology domain. RT–PCR analysis revealed that significantly higher SjVAMP2 levels were observed in 14-, 28- and 42-day-old worms, and SjVAMP2 expression was much higher in 42-day-old female worms than in those male worms. Additionally, the expression of SjVAMP2 was associated with membrane recovery in PZQ-treated worms. Immunostaining assay showed that SjVAMP2 was mainly distributed in the sub-tegument of the worms. Western blotting revealed that rSjVAMP2 showed strong immunogenicity. Purified rSjVAMP2 emulsified with ISA206 adjuvant induced 41.5% and 27.3% reductions in worm burden, and 36.8% and 23.3% reductions in hepatic eggs in two independent trials. Besides, significantly higher rSjVAMP2-specific IgG, IgG1, IgG2a levels were detected in rSjVAMP2-vaccinated mice. Conclusion: Our study indicated that SjVAMP2 is a potential vaccine candidate against S. japonicum and provided the basis for further investigations into the biological function of SjVAMP2. [ABSTRACT FROM AUTHOR]

In the present study, a full-length cDNA encoding the Schistosoma japonicum 3-phosphoglycerate kinase (SjPGK) with an open reading frame of 1251 bp was isolated from 42-day-old (42-d) schistosome cDNAs. Real-time quantitative reverse transcription PCR analysis revealed that SjPGK was expressed in all investigated developmental stages and at a higher transcript levels in 21- and 42-d worms. Moreover, the SjPGK mRNA level was significantly downregulated in 10-d schistosomula from Wistar rats (non-susceptible host). SjPGK was subcloned into pET28a(+) and expressed as both supernatant and inclusion bodies in Escherichia coli BL21 cells. The enzymatic activity of recombinant SjPGK protein (rSjPGK) was 125 U/mg. Kinetic analyses with respect to 3-phosphoglycerate (3-PGA) as substrate gave a Km of 2.69 mmol/L and a Vmax of 748 μmol/min/mg protein. rSjPGK was highly stable over a range of pH 8.0–9.0 and temperature of 30°C-40 °C under physiological conditions. Immunolocalization analysis showed that SjPGK was mainly distributed in the tegument and parenchyma of schistosomes. Western blotting showed that rSjPGK had good immunogenicity. We vaccinated BALB/c mice with rSjPGK combined with Seppic 206 adjuvant. However, there were no significant reductions in the numbers of worms of eggs in the liver, as compared to adjuvant or blank control groups in two independent vaccination tests. This study provides the basis for further investigations into the biological function of SjPGK, although it might not be suitable as a potential vaccine candidate against schistosomiasis. [ABSTRACT FROM AUTHOR]

Ultrafast fluorescence dynamics of Tryptophan–Tryptophan (Trp–Trp/Trp 2 ) dipeptide and its derivatives in water have been investigated using a picosecond resolved time correlated single photon counting (TCSPC) apparatus together with a femtosecond resolved upconversion spectrophotofluorometer. The fluorescence decay profiles at multiple wavelengths were fitted by a global analysis technique. Nanosecond fluorescence kinetics of Trp 2 , N-tert-butyl carbonyl oxygen-N′-aldehyde group- l -tryptophan- l -tryptophan (NBTrp 2 ), l -tryptophan- l -tryptophan methyl ester (Trp 2 Me), and N-acetyl- l -tryptophan- l -tryptophan methyl ester (NATrp 2 Me) exhibit multi-exponential decays with the average lifetimes of 1.99, 3.04, 0.72 and 1.22 ns, respectively. Due to the intramolecular interaction between two Trp residues, the “water relaxation” lifetime was observed around 4 ps, and it is noticed that Trp 2 and its derivatives also exhibit a new decay with a lifetime of ∼100 ps, while single-Trp fluorescence decay in dipeptides/proteins shows 20–30 ps. The intramolecular interaction lifetime constants of Trp 2 , NBTrp 2 , Trp 2 Me and NATrp 2 Me were then calculated to be 3.64, 0.93, 11.52 and 2.40 ns, respectively. Candidate mechanisms (including heterogeneity, solvent relaxation, quasi static self-quenching or ET/PT quenching) have been discussed. [ABSTRACT FROM AUTHOR]

The aim of this study was to search for immunogenic schistosomula proteins in the hope of identifying novel intervention targets. Schistosomula proteins were analyzed by immunoproteomic which the probes were sera derived from BALB/c mice (susceptible hosts) and Microtus fortis (resistant hosts). A total of 116 immunoreactive proteins recognized by 10 days post-infected BALB/c mice, M. fortis sera, and uninfected M. fortis sera were selected for further analysis. Finally, 95 protein spots were identified by mass spectrometry (MS) analysis. Bioinformatics analysis showed that the differentially identified immunogenic proteins participated mainly in cytoskeleton organization, cell motility, energy metabolism, responses to stimuli, and protein folding. Many of these proteins were the tegument or excretory–secretory products of schistosomes reported in previous studies. Among of them, Schistosoma japonicum DnaJ (Hsp40) homologue (SjDnaJ) was successfully expressed and the purified recombinant product was evaluated by immunoprotective experiment. After immunization of BALB/c mice with recombinant SjDnaJ, it could induce 34.5% and 48.9% reductions in the numbers of worms and eggs in the liver. These results contribute to a better understanding of the molecular mechanisms underlying the host–parasite relationship and provide a major dataset to facilitate the further development of new vaccine candidates and/or diagnostic markers for schistosomiasis. Biological significance Schistosomiasis is caused by parasitic blood-dwelling flukes in tropical and subtropical areas, and it is one of the world's most prevalent tropical diseases. The lack of effective vaccine and reliable diagnostic methods make this disease difficult to control. In China, S. japonicum can infect more than 40 different susceptible mammals for this parasite. However, M. fortis is the only known mammal where the schistosome cannot develop and it exhibits no significant pathological effects. Many studies' results showed that native antibodies against S. japonicum are present in M. fortis that may have important anti-schistosomiasis roles during the infection process. The aim of this study was to search for immunogenic schistosomula proteins in the hope of identifying novel intervention targets. We present a comparative immunoproteomics analysis of the proteins recognized by susceptible and resistant host antibodies before and 10-days after infections. The results of this analysis will be helpful for identifying the key molecules required for the survival and development of schistosomes. At the same time, the study contributes to a better understanding of the molecular mechanisms underlying the host–parasite relationship associated with schistosomes and they also provide a major dataset to facilitate the further development of new diagnostic assays and/or vaccine candidates for schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is one of the world's most prevalent zoonotic diseases and a serious worldwide public health problem. Since the tegument (TG) of Schistosoma japonicum is in direct contact with the host and induces a host immune response against infection, the identification of immune response target molecules in the schistosome TG is crucial for screening diagnostic antigens for this disease. Methodology/Principal Findings: In this study, an immunoproteomics approach used TG proteins as screening antigens to identify potential diagnostic molecules of S. japonicum. Ten spots corresponding to six proteins were identified that immunoreacted with sera from S. japonicum-infected rabbits but not sera from uninfected rabbits and their specific IgG antibody levels declined quickly after praziquantel treatment. Recombinant phosphoglycerate mutase (PGM) and UV excision repair protein RAD23 homolog B (RAD23) proteins were expressed and their diagnostic potential for schistosomiasis was evaluated and compared with schistosome soluble egg antigen (SEA) using ELISA. The results showed high sensitivity and specificity and low crossreactivity when rSjPGM-ELISA and rSjRAD23-ELISA were used to detect water buffalo schistosomiasis. Moreover, antibodies to rSjPGM and rSjRAD23 might be short-lived since they declined quickly after chemotherapy. Conclusion/Significance: Therefore, the two schistosome TG proteins SjPGM and SjRAD23 were identified as potential diagnostic markers for the disease. The two recombinant proteins might have the potential to evaluate the effectiveness of drug treatments and for distinguishing between current and past infection. Author Summary: As one of the world's most prevalent zoonotic diseases, schistosomiasis remains a serious worldwide public health problem. An immunoproteomics approach was used to identify potential immune diagnostic molecules from S. japonicum TG proteins extracted from adult schistosomes. Probes were derived from sera collected from uninfected rabbits and rabbits at 2 and 6 weeks after infection with S. japonicum as well as praziquantel-treated rabbits. SjPGM and SjRAD23 were identified as potential diagnostic markers for the disease. High sensitivity and specificity and low crossreactivity were observed for rSjPGM-ELISA and rSjRAD23-ELISA, which were used to detect water buffalo schistosomiasis. In addition, these two proteins induced a short-lived antibody response since specific IgG antibodies to them declined quickly after chemotherapy and had the potential to be used to evaluate the effectiveness of chemotherapy against S. japonicum. Our study provides information for screening potential diagnostic antigens and establishing more sensitive schistosomiasis diagnosis techniques. [ABSTRACT FROM AUTHOR]

Studying cell microstructures and their behaviors under living conditions has been a challenging subject in microbiology. In this work, in situ liquid chamber TEM was used to study structures of Escherichia coli cells in aqueous solutions at a nanometer-scale resolution. Most of the cells remained intact under electron beam irradiation, and nanoscale structures were observed during the TEM imaging. The analysis revealed structures of pili surrounding the E. coli cells; the movements of the pili in the liquid were also observed during the in situ tests. This technology also allowed the observation of features of the nucleoid in the E. coli cells. Overall, in situ TEM can be applied as a valuable tool to study real-time microscopic structures and processes in microbial cells residing in native aqueous solutions. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is one of the world’s most prevalent zoonotic diseases and a serious worldwide public health problem. Since the tegument (TG) of Schistosoma japonicum is in direct contact with the host and induces a host immune response against infection, the identification of immune response target molecules in the schistosome TG is crucial for screening diagnostic antigens for this disease. Methodology/Principal Findings: In this study, an immunoproteomics approach used TG proteins as screening antigens to identify potential diagnostic molecules of S. japonicum. Ten spots corresponding to six proteins were identified that immunoreacted with sera from S. japonicum-infected rabbits but not sera from uninfected rabbits and their specific IgG antibody levels declined quickly after praziquantel treatment. Recombinant phosphoglycerate mutase (PGM) and UV excision repair protein RAD23 homolog B (RAD23) proteins were expressed and their diagnostic potential for schistosomiasis was evaluated and compared with schistosome soluble egg antigen (SEA) using ELISA. The results showed high sensitivity and specificity and low crossreactivity when rSjPGM-ELISA and rSjRAD23-ELISA were used to detect water buffalo schistosomiasis. Moreover, antibodies to rSjPGM and rSjRAD23 might be short-lived since they declined quickly after chemotherapy. Conclusion/Significance: Therefore, the two schistosome TG proteins SjPGM and SjRAD23 were identified as potential diagnostic markers for the disease. The two recombinant proteins might have the potential to evaluate the effectiveness of drug treatments and for distinguishing between current and past infection. [ABSTRACT FROM AUTHOR]

Summary To successfully colonize and persist within a host niche, bacteria must properly regulate their gene expression profiles. The marine bacterium Vibrio fischeri establishes a mutualistic symbiosis within the light organ of the Hawaiian squid, Euprymna scolopes. Here, we show that the repressor NagC of V. fischeri directly regulates several chitin- and N-acetyl- d-glucosamine-utilization genes that are co-regulated during productive symbiosis. We also demonstrate that repression by NagC is relieved in the presence of N-acetyl- d-glucosamine-6-phosphate, the intracellular form of N-acetyl- d-glucosamine. We find that gene repression by NagC is critical for efficient colonization of E. scolopes. Further, our study shows that NagC regulates genes that affect the normal dynamics of host colonization. [ABSTRACT FROM AUTHOR]

Vibrio alginolyticus, a marine bacterium, is an opportunistic pathogen capable of causing vibriosis with high mortality to fishes in the South China Sea. Stress resistance is very important for its survival in the natural environment and upon infection of the host. RpoS, an alternative sigma factor, is considered as an important regulator involved in stress response and virulence in many pathogens. In this study, the rpoS gene was cloned and characterized to evaluate the role of RpoS in V. alginolyticus. The predicted protein showed high identity with other reported rpoS gene products. The in-frame deleted mutation of rpoS in V. alginolyticus led to sensitivity of the strain to ethanol, hyperosmolarity, heat, and hydrogen peroxide challenges. Further studies showed that extracellular autoinducer 2 level, four of seven detected protease activities, and cytotoxicity of extracellular products were markedly decreased in the rpoS mutant compared with that in the wild-type strain. The results indicated that the global regulator RpoS was part of the regulatory networks of virulence and LuxS quorum sensing system. [ABSTRACT FROM AUTHOR]

Background: In China, although buffaloes are abundant, beef is mainly obtained from cattle, and this preference is mainly attributed to the low intramuscular fat (IMF) content of buffalo. Genetic factors are an important driver that affects IMF deposition. Results: To reveal the intrinsic factors responsible for the low IMF content of buffalo, mRNA expression patterns in muscle and adipose tissue between buffalo and cattle were characterized by RNA sequencing analysis. The IMF content in Nanyang cattle was higher than that in Xinyang buffalo. A total of 1566 mRNAs expressed in adipose tissue showed differential expression between the longissimus dorsi muscles of buffalo and cattle. Functional annotation suggested a difference in the glycolysis/gluconeogenesis pathway between the two species. The results of RT-qPCR analysis and gain-of-function experiments confirmed the positive association between the IMF content and phosphoenolpyruvate carboxykinase 1 (PCK1) expression in buffalo. In both mouse C2C12 cells and cultured bovine myocytes, the activity of the PCK1 promoter in buffalo is lower than that in cattle. However, in mouse 3T3-L1 adipocytes and cultured bovine adipocytes, the activity of PCK1 in buffalo promoter is higher than that in cattle. Conclusions: These results indicate the important role of PCK1 in buffalo IMF deposition and illustrate the differences between buffalo and cattle promoter activity that drive PCK1 expression. This research helps to establish a foundation for further studies investigating IMF deposition in buffalo. [ABSTRACT FROM AUTHOR]

Current treatment of rheumatoid arthritis (RA) is limited by relative shortage of treatment targets. HM-3 is a novel anti-RA polypeptide consisting of 18 amino acids with integrin αVβ3 and α5β1 as targets. Previous studies confirmed that HM-3 effectively inhibited the synovial angiogenesis and the inflammatory response. However, due to its short half-life, the anti-RA activity was achieved by frequent administration. To extend the half-life of HM-3, we designed a fusion protein with name HM-3-Fc, by combination of modified Fc segment of immunoglobulin 4 (IgG4) with HM-3 polypeptide. In vitro cell experiments demonstrated that HM-3-Fc inhibited the proliferation of splenic lymphocytes and reduced the release of TNF-α from macrophages. The pharmacodynamics studies on mice paw in Collagen-Induced Arthritis (CIA) model demonstrated that HM-3-Fc administered once in 5 days in the 50 and 25 mg/kg groups, or once in 7 days in the 25 mg/kg group showed a better protective effect within two weeks than the positive control adalimumab and HM-3 group. Preliminary pharmacokinetic studies in cynomolgus confirmed that the in vivo half-life of HM-3-Fc was 15.24 h in comparison with 1.32 min that of HM-3, which demonstrated that an Fc fusion can effectively increase the half-life of HM-3 and make it possible for further reduction of subcutaneous injection frequency. Fc-HM-3 is a long-acting active molecule for RA treatment. [ABSTRACT FROM AUTHOR]