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Total dissolved gas (TDG) supersaturation caused by flood discharge water poses a threat to vital activities such as migration, foraging, and evasion in fish species upstream of the Yangtze River, which may impair the ability of fish to pass through fishways during the migration period, causing poor utilization of fishways. Previous studies have shown that TDG supersaturation reduces the critical and burst swimming abilities of fish, suggesting potential adverse effects on swimming performance. However, studies focusing on the impact of TDG on fish swimming behavior in experimental vertical-slot fishways remain scarce. Therefore, in this study, silver carp (Hypophthalmichthys molitrix) and ya-fish (Schizothorax prenanti) were used as the study species, and comparative passage experiments were carried out in an experimental vertical slot fishway to systematically analyze the effects of TDG supersaturation on their passage behavior. The passage success of the silver carp was 57%, 39%, 26%, and 27% at TDG levels of 100%, 110%, 120%, and 130%, respectively. Passage success of ya-fish was 73%, 37%, 31%, and 35% at TDG concentrations of 100%, 110%, 120%, and 130%, respectively. The passage time for both species increased significantly with increasing TDG levels. Furthermore, the passage routes of silver carp changed significantly compared to the control group, whereas the passage routes of ya-fish changed insignificantly. High levels of TDG supersaturation (≥120%) also contributed to a higher mortality rate of ya-fish passing through the vertical slot fishway. The research results provide valuable data on the influence of TDG supersaturation on fish movement behavior responses in experimental vertical slot fishways, offering a reference for the design of fishways and the formulation of reservoir operation schemes. [Display omitted] ● The passage behavior of two species through an experimental fishway after 2-hour TDG-supersaturated exposure was analyzed. ● The passage success, passage time, and passage routes of two species under four TDG levels were analyzed. ● TDG supersaturation exacerbates fish mortality through an experimental fishway, with differential effects among species. ● Higher TDG levels (≥120%) cause more severe injuries to fish migration and less effective use of fish passage engineering. [ABSTRACT FROM AUTHOR]

Osteosarcoma, considered as the primary cause of malignant bone tumors in children, necessitates novel therapeutic strategies to enhance overall survival rates. KAT7, a histone acetyltransferase, exerts pivotal functions in gene transcription and immune modulation. In light of this, our study identified a significant upregulation of KAT7 in the mRNA and protein levels in human osteosarcoma, boosting cell proliferation in vivo and in vitro. In addition, KAT7-mediated H3K14ac activation induced MMP14 transcription, leading to increased expression and facilitation of osteosarcoma cell metastasis. Subsequent bioinformatics analyses highlighted a correlation between KAT7 and adaptive immune responses, indicating CCL3 as a downstream target of KAT7. Mechanistically, STAT1 was found to transcriptionally upregulate CCL3 expression. Furthermore, overexpression of KAT7 suppressed CCL3 secretions, whereas knockdown of KAT7 enhanced its release. Overall, these findings underscore the oncogenic role of KAT7 in regulating immune responses for osteosarcoma treatment. • KAT7 was abundantly expressed in osteosarcoma. • KAT7 overexpression enhanced the expression of MMP14 by H3K14ac modification. • KAT7 inhibited the expression of CCL3 via JAK1-STAT1 signaling pathways. • STAT1 transcriptionally activated CCL3, thereby modulating immune responses. • KAT7 accelerated dissemination of OS cells in vivo. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the mostly diagnosed primary bone malignancy. Emerging evidence indicates that the activity of pyruvate kinase M2 (PKM2) isoform is crucial for the survival of tumor cells. In the present study, the effect of PKM2 knockdown on the proliferation and migration of OS cells were assessed both in vitro and in vivo . Small hairpin RNA (shRNA) technology were employed to suppress the expression of PKM2 in MG-63 and Saos-2 cell lines. In vitro , shRNA-mediated knockdown of PKM2 efficiently inhibited cell proliferation, and induced G1 cell cycle arrest and apoptosis in both cell lines, which was associated with decreased expressions of cyclin D1 and Bcl-2 as well as increased expressions of Bax, cleaved-caspase-3, and cleaved-PARP. The invasion and migration potential of OS cell lines were also inhibited by PKM2 knockdown through the regulating effect of PKM2 on MMP-2 and VEGF signaling. In vivo , knockdown of PKM2 decelerated tumor growth rate and induced structure deterioration in tumor tissues. The current study for the first time showed that the activity of PKM2 was indispensable for the development and metastasis of OS, thereby providing the basic information for the future development of PKM2-based anti-OS therapies. [ABSTRACT FROM AUTHOR]

The binding of organic chemicals to serum albumin can significantly reduce their unbound concentration in blood and affect their biological reactions. In this study, we developed a new QSAR model for bovine serum albumin (BSA) – water partition coefficients ( K BSA/W ) of neutral organic chemicals with large structural variance, log K BSA/W values covering 3.5 orders of magnitude (1.19–4.76). All chemical geometries were optimized by semi-empirical PM6 algorithm. Several quantum chemical parameters that reflect various intermolecular interactions as well as hydrophobicity were selected to develop QSAR model. The result indicates the regression model derived from log K ow , the most positive net atomic charges on an atom, Connolly solvent excluded volume, polarizability, and Abraham acidity could explain the partitioning mechanism of organic chemicals between BSA and water. The simulated external validation and cross validation verifies the developed model has good statistical robustness and predictive ability, thus can be used to estimate the log K BSA/W values for chemicals in application domain, accordingly to provide basic data for the toxicity assessment of the chemicals. [ABSTRACT FROM AUTHOR]

Abstract: The problem of finding the optimal approximation to analytical stiffness matrix modeled by the finite element method is considered in this paper. Desired matrix properties, including satisfaction of the dynamic equation, symmetry, positive semidefiniteness and physical connectivity, are imposed as side constraints of the minimization problem. To the best of the author''s knowledge, the finite element model updating problem containing all these constraints simultaneously has not been proposed in the literature earlier. By partial Lagrangian multipliers technique, the optimization problem is transformed into a matrix linear variational inequality and the proximal-point method is first used to solve the equivalent problem. The results of numerical examples show that the proposed method works well even for incomplete measured data. [Copyright &y& Elsevier]

Abstract: The problem of finding the least change adjustment to analytical stiffness matrix modeled by finite element method is considered in this paper. Desired matrix properties, including satisfaction of the dynamic equation, symmetry, positive semidefiniteness and sparse pattern, are imposed as side constraints of the nonlinear optimization problem. To the best of the author''s knowledge, the matrix updating problem containing all these constraints simultaneously has not been proposed in the literature earlier. By partial Lagrangian multipliers technique, the optimization problem is first reformulated as an equivalent matrix linear variational inequality (MLVI) and solved by extended projection and contraction method. The results of numerical examples show that the proposed method works well even for incomplete measured data. [Copyright &y& Elsevier]

Abstract: The nanoscience and nanotechniques have brought with new chance for new applications of some traditional materials, for instance, ceria-based materials, which are of great interest due to their wide applications, in particular, as redox or oxygen storage promoters in the three-way catalysts, catalysts for H2 production from fuels, and solid state conductors for fuel cells. We highlight here current research activities focused on the controlled synthesis and assembly of ceria-based nanomaterials. We begin with a brief introduction to the urgency for research of ceria-based nanomaterials and our different consideration. Typical synthesis is then discussed with examples of nanosized ceria, ceria–zirconia solid solutions, and doped ceria developed by our group and the others. Controlled synthesis to manipulate the shape, crystal plane, and size is the topic of this article, with approaches elaborated for the assembly of ceria-based materials. Finally, we conclude this article with personal understandings and perspectives on this exciting realm. [Copyright &y& Elsevier]

Abstract: The apparent molar volumes of l-alanine, dl-serine, dl-threonine, l-histidine, glycine, and glycylglycine in water and in the aqueous solutions of NaCl and DMSO with various concentrations at T =298.15 K have been measured by the precise vibrating-tube digital densimeter. The calculated partial molar volumes at infinite dilution have been used to obtain corresponding transfer volumes from water to various solutions. The experimental results show that the standard partial molar volumes of the above amino acids and peptide at the dilute DMSO aqueous solutions are very close to those in water. However, the volumes show several types of variations with the increase of the concentrations of DMSO due to different types of side chain of amino acids, which should be discussed specifically. The NaCl changes considerably the infinite dilution standard partial molar volumes of the above amino acids and peptide in the aqueous solutions. The infinite dilution standard partial molar volumes of the each amino acids and peptide increase with the concentrations of NaCl. The experimental results have been rationalized by a cosphere overlap model. [Copyright &y& Elsevier]

Total dissolved gas (TDG) supersaturation caused by dam operations can cause fish gas bubble disease (GBD) and even fish kill. Few studies have examined the effects on pelagic species. Here, we examined the tolerance and avoidance characteristics of silver carp (Hypophthalmichthys molitrix), a pelagic fish widely distributed in the Yangtze River basin in China, under stress caused by TDG supersaturation. Silver carp had an average mortality rate of 7.5% ± 1.8%, 92.5% ± 1.8%, and 97.5% ± 1.8% under 130%, 140% and 150% TDG supersaturation for 72 h of exposure, respectively. The average median lethal time (LT 50) of silver carp was 18.1 h and 8.0 h under 140% and 150% TDG supersaturation, respectively. Bubbles and congestion appeared in the fins, gills and skin of silver carp. Silver carp can detect and avoid high TDG supersaturation. Significant avoidance behaviors were displayed by silver carp and the final avoidance rate was over 80% under 130% or above TDG conditions. The results of this study indicate that 130% TDG supersaturation triggered silver carp avoidance behaviors, and can be considered as the tolerance threshold. • Silver carp in TDG supersaturated water appeared obvious signs of GBD. • Silver carp died when TDG supersaturation was over 130%. • 130% TDG supersaturation triggered silver carp avoidance behaviors. • 130% TDG supersaturation can be considered as the tolerance threshold for silver carp. [ABSTRACT FROM AUTHOR]

Cardiac dysfunction is a common adverse effect of subarachnoid hemorrhage (SAH). Autopsy of SAH patients shows immunocyte infiltration into the heart. In this study, a SAH model of endovascular perforation was performed in adult male mice in order to test whether SAH causes cardiac dysfunction in non-primary cardiac disease young adult male mice and whether immune response mediates SAH induced cardiac and neurological deficit. Splenectomy was performed on a subpopulation of mice one week prior to induction of the SAH. Neurological functional tests, transthoracic Doppler echocardiography, immunofluorescent staining, and flow cytometry were performed to investigate neurological and cardiac function and immune/inflammatory effects of SAH in mice with or without splenectomy. We found that SAH significantly induces ventricular fibrillation and cardiac dysfunction identified by significantly reduced left ventricular ejection fraction, left ventricular fractional shortening, decreased heart rate, as well as increased macrophage and neutrophil infiltration into heart and inflammatory factor expression in the heart compared to sham control mice. SAH also induces neurological deficit, increases astrocyte and microglial activity, and inflammatory cell infiltration into brain as well as up-regulates inflammatory factor expression in the brain tissue. Splenectomy not only significantly improves neurological function, but also reduces cardiac dysfunction compared to SAH alone mice. Splenectomy in SAH mice significantly reduces inflammatory cell infiltration, and decreases NADPH oxidase-2 and macrophage chemokine protein-1 expression in heart and brain when compared to non-splenectomy SAH mice. Our data suggest that, SAH induces acute cardiac dysfunction in non-primary cardiac disease mice. Secondary immune response may play an important role in mediating brain-heart damage after SAH. [ABSTRACT FROM AUTHOR]

Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly. Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated. In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV). Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells. However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines. Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV. [ABSTRACT FROM AUTHOR]

Abstract: Escherichia coli single-stranded DNA binding protein (SSB) plays essential roles in DNA replication, recombination and repair. SSB functions as a homotetramer with each subunit possessing a DNA binding domain (OB-fold) and an intrinsically disordered C-terminus, of which the last nine amino acids provide the site for interaction with at least a dozen other proteins that function in DNA metabolism. To examine how many C-termini are needed for SSB function, we engineered covalently linked forms of SSB that possess only one or two C-termini within a four-OB-fold “tetramer”. Whereas E. coli expressing SSB with only two tails can survive, expression of a single-tailed SSB is dominant lethal. E. coli expressing only the two-tailed SSB recovers faster from exposure to DNA damaging agents but accumulates more mutations. A single-tailed SSB shows defects in coupled leading and lagging strand DNA replication and does not support replication restart in vitro. These deficiencies in vitro provide a plausible explanation for the lethality observed in vivo. These results indicate that a single SSB tetramer must interact simultaneously with multiple protein partners during some essential roles in genome maintenance. [Copyright &y& Elsevier]

The production of highly purified native soluble proteins in large quantities is crucial for studying protein structure and function. Odorant binding proteins (OBPs) are small, soluble, extracellular proteins with multiple disulfide bonds, whose functions include, but are not limited to, binding hydrophobic molecules and delivering them to their corresponding receptors expressed on insect olfactory receptor neurons. Expression of proteins with multiple disulfide bonds like OBPs usually results in insolubility and low yield, which has been a significant barrier to understanding their biological roles and physiological functions. In the E. coli system, expression of OBPs often results in insoluble inclusion bodies or a limited amount of periplasmic soluble proteins. Although expression of OBPs in eukaryotic systems such as Sf9 insect cells or yeast Pichia pastoris can increase the solubility of the protein, the process remains insufficient. Additionally, monitoring the purity and native apo state of the protein is critical for establishing the correct conformation of the protein. In this study, we employed an E. coli host with an altered intracellular environment to produce cytosolic soluble OBP44a protein, which yielded over 100 mg/L. We monitored the integrity of disulfide bonds throughout the purification process using LC-MS and used NMR to ensure the final product adopted a single conformation. Our study presents an efficient method for obtaining large quantities of soluble proteins in a single conformation, which enables extensive in vitro studies of secreted proteins like OBPs. • Expressed OBP44a, a protein with two disulfide bonds, as cytosolic soluble protein using SHuffle E.coli. • Achieved OBP44a yield of 100 mg/L using fermentation. • Monitored integrity of disulfide bonds using LC-MS. • Guaranteed single protein conformation using NMR. [ABSTRACT FROM AUTHOR]

• Ketogenic diet ameliorates social defeat and LPS-induced depressive-like behaviors. • Ketogenic diet rescues neuronal excitability defect in the LHb of depression mice. • Microglial inflammatory activation is elevated in the LHb of depression mice. • Ketogenic diet reduces microglial inflammatory activation in the LHb. • Knockdown of Trem2 in the LHb microglia causes depressive-like behaviors. Depression is a severe neuropsychiatric disorder, of which the underlying pathological mechanisms remain unclear. The ketogenic diet (KD) has been reported to exhibit preventative effects on depressive-like behaviors in rodents. However, the therapeutic effects of KD on depressive-like behaviors have not been illustrated thus far. Here, we found that KD treatment dramatically ameliorated depressive-like behaviors in both repeated social defeat stress (R-SDS) and lipopolysaccharide (LPS) models, indicating the potential therapeutic effects of KD on depression. Our electrophysiological studies further showed that neuronal excitability was increased in the lateral habenula (LHb) of mice exposed to R-SDS or LPS, which can be reversed in the presence of KD treatment. Moreover, R-SDS and LPS were also found to induce robust microglial inflammatory activation in the LHb. Importantly, these phenotypes were rescued in mice fed with KD. In addition, we found that the protein level of innate immune receptor Trem2 in the LHb was significantly decreased in depression models. Specific knockdown of Trem2 in LHb microglia induced depressive-like behaviors, increased neuronal excitability as well as robust microglial inflammatory activation. Altogether, we demonstrated the therapeutic effects of KD on depressive-like behaviors, which are probably mediated via the restoration of microglial inflammatory activation and neuronal excitability. Besides, we also proposed an unrecognized function of Trem2 in the LHb for depression. Our study sheds light on the pathogenesis of depression and thereby offers a potential therapeutic intervention. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate the long-term spatiotemporal changes in hydrodynamics, antibiotics, nine typical subtypes of antibiotic resistance genes (ARGs), class 1 integron gene (intI1), and microbial communities in the sediments of a semi-enclosed estuary during ecological restoration with four treatment stages (influent (#1), effluent of the biological treatment area (#2), oxic area (#3), and plant treatment area (#4)). Ecological restoration of the estuary reduced common pollutants (nitrogen and phosphorus) in the water, whereas variations in ARGs showed noticeable seasonal and spatial features. The absolute abundance of ARGs at sampling site #2 considerably increased in autumn and winter, while it significantly increased at sampling site #3 in spring and summer. The strong intervention of biological treatment (from #1 to #2) and aerators (from #2 to #3) in the estuary substantially affected the distribution of ARGs and dominant antibiotic-resistant bacteria (ARB). The dominant ARB (Thiobacillus) in estuarine sediments may have low abundance but important dissemination roles. Meanwhile, redundancy and network analysis revealed that the microbial communities and intl1 were key factors related to ARG dissemination, which was affected by spatial and seasonal ecological restoration. A positive correlation between low flow velocity and certain ARGs (tetM , tetW , tetA , sul2 , and ermC) was observed, implying that flow optimization should also be considered in future ecological restoration to remediate ARGs. Furthermore, the absolute abundance of ARGs can be utilized as an index to evaluate the removal capacity of ARGs by estuarine restoration. [Display omitted] • Effects of ecological restoration on ARG distribution in sediment were investigated. • The sul1 , tetA , ermB , ermC and floR were dominant ARGs in the estuary sediments. • Microbial genera in Proteobacteria were dominant ARBs in the estuary sediments. • Microbial communities and intl1 were key factors related to the ARG dissemination. • ARGs dissemination was affected by ecological restoration spatially and seasonally. [ABSTRACT FROM AUTHOR]

This study investigated ultrafiltration membrane fouling by extracellular organic matter (EOM) and the mechanism operating during long-term exposure to pharmaceuticals and personal care products. The results indicated that carbamazepine and diclofenac in algal-laden water altered the filtration flux and membrane fouling by EOM. Exposure to low-concentration carbamazepine (0.25 μg/L) improved the filtration flux and the total (R tot) and reversible fouling resistance (R c), whereas the filtration flux and R tot and R c were reduced when EOM was used during long-term exposure to high carbamazepine concentrations (>1 μg/L). Both R tot and R c were increased when algae were exposed to 0.25 μg/L diclofenac, whereas the filtration flux and R tot and R c were alleviated when algae were exposed to >1 μg/L diclofenac. Moreover, carbamazepine and diclofenac (0.25 μg/L − 1000 μg/L) in water enhanced the irreversible fouling resistance (R b) when ultrafiltration was used to treat algal-laden waters. The mechanism indicated that membrane fouling induced by standard blocking was transformed to complete blocking when EOM was exposed to high levels of carbamazepine (>0.25 μg/L) in the initial filtration process, whereas cake layer formation played an important role during the later filtration process; with low carbamazepine levels (0.25 μg/L), standard blocking of EOM was dominant during the entire filtration process. The membrane fouling mechanism also changed when algal-laden waters were exposed to diclofenac, the membrane fouling was transformed from complete blocking to standard blocking when DFC was present in the initial filtration process, whereas cake layer formation exerted an important role during the late filtration process. This research provides important information on the long-term risks caused by pharmaceutical and personal care products and potential threats to membrane treatment. • CMZ and DFC treatments of algal-laden water altered filtration flux and membrane fouling of EOM. • R ir were enhanced when CMZ and DFC existed in water. • Membrane fouling mechanism was changed when algal-laden water exposed to various PPCPs. [ABSTRACT FROM AUTHOR]

Mammalian cysteine dioxygenase type 1 (CDO1) is an essential enzyme for taurine biosynthesis and the biodegradation of toxic cysteine. As previously suggested, Cdo1 may be a marker of liposarcoma progression and adipogenic differentiation, but the role of Cdo1 in adipogenesis has yet been reported. In this study, we found that the expression of Cdo1 is dramatically elevated during adipogenic differentiation of 3T3-L1 pre-adipocytes and mouse bone marrow-derived mesenchymal stem cells (mBMSCs). Conversely, knockdown of Cdo1 inhibited expression of adipogenic specific genes and lipid droplet formation in 3T3-L1 cells and mBMSCs. Mechanistically, we found Cdo1 interacted with Pparγ in response to adipogenic stimulus. Further, depletion of Cdo1 reduced the recruitment of Pparγ to the promoters of C/EBPα and Fabp4. Collectively, our finding indicates that Cdo1 may be a co-activator of Pparγ in adipogenesis, and may contribute to the development of disease associated with excessive adipose tissue. [ABSTRACT FROM AUTHOR]

Abstract: Polyphosphate (polyP) is composed of linear polymers of orthophosphate residues linked by high-energy phosphoanhydride bonds. It has been reported to improve osteoblastic differentiation, stimulate periodontal tissue regeneration, and accelerate bone repair. The aim of this study was to evaluate the effect of polyP on the expression of FGF23, a hormone secreted mostly be mature osteoblasts and osteocytes. In this study, different types of polyP were synthesized and co-cultured with osteoblast-like UMR-106 cells. Real-time PCR and western blot were used to analyze the gene and protein expression of FGF23. We found that 1mM polyP was able to increase FGF23 expression after 4h, reaching a peak after 12–24h, with expression decreasing by 48h. We also found that polyP could activate the FGFR pathway, as evidenced by increased phosphorylation of FGFR, FRS2, and Erk1/2. When FGFR signaling was inhibited by the specific inhibitor SU5402, the effect of polyP on FGF23 expression was significantly reduced. Our results indicate that polyP is able to stimulate osteoblastic FGF23 expression and that this effect is associated with activation of the FGFR pathway. These findings provide support for the clinical use of polyP by indicating a mechanism for polyP in bone regeneration. [Copyright &y& Elsevier]

Background: Segmental bone defect is still a challenge to orthopedic surgeons. Currently available therapies for segmental bone defects have some drawbacks. Tissue engineering using pluripotent stem cells is a new, promising method for bone repair. The present study aims to promote the effect of bone defect repair using the tissue engineered bone in combination with vascularized periosteal flaps. Methods: The adenoviral vector carrying Cbfa1 transduced rabbit adipose-derived mesenchymal stem cells and gene modified tissue engineering bone (GMB) were constructed. Rabbits with radial defects were implanted with the GMB together with vascularized periosteum (group A); or GMB with free periosteum (group B); or GMB (group C), and scaffold (group D). The bone repair effect was evaluated at 4, 8, or 12 wk, respectively, after the operations. Results: Cbfa1 proteins were strongly expressed in adipose stem cells (ADSCs) that formed a stratified network on the inner surface of the polylactic acid/ polycaprolacton (PLA/PCL) pores. Bone repair was well achieved in the rabbits treated with the Cbfa1-expressing ADSCs and vascularized flap that was markedly better than those treated with either Cbfa1-expressing ADSCs alone or with vascularized flap alone. Conclusions: Combination with implanting the Cbfa1 gene-modified tissue-engineered bone and vascularized periosteum can better repair the segmental bone defects by stimulating osteogenesis, osteoinduction, and osteoconduction than using either one of the approaches. [Copyright &y& Elsevier]