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Itch and pain are two closely related sensations that receiving similar encodings at multiple levels. Accumulated evidences suggest that activation of the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL)-to-lateral and ventrolateral periaqueductal gray (l/vlPAG) projections mediates the antinociceptive effects of bright light therapy. Clinical study showed that bright light therapy may ameliorate cholestasis-induced pruritus. However, the underlying mechanism and whether this circuit participates in itch modulation remains unclear. In this study, chloroquine and histamine were utilized to induce acute itch models in mice. Neuronal activities in vLGN/IGL nucleus were evaluated with c -fos immunostaining as well as fiber photometry. Optogenetic manipulations were performed to activate or inhibit GABAergic neurons in the vLGN/IGL nucleus. Our results showed that the expressions of c -fos in vLGN/IGL were significantly increased upon both chloroquine- and histamine-induced acute itch stimuli. GABAergic neurons in vLGN/IGL were activated during histamine and chloroquine-induced scratching. Optogenetic activation of the vLGN/IGL GABAergic neurons exerts antipruritic effect, while inhibiting these neurons exerts pruritic effect. Our results provide evidence that GABAergic neurons in vLGN/IGL nucleus might play a crucial role in modulating itch, which may provide clue for application of bright light as an antipruritic treatment in clinic. • Expressions of c -fos in vLGN/IGL are significantly increased upon both chloroquine- and histamine-induced acute itch stimuli. • The calcium signal activity of GABA neurons in the vLGN/IGL is increased after acute itch stimuli. • VLGN/IGL GABAergic neurons regulate chloroquine- and histamine-induced itching behavior. [ABSTRACT FROM AUTHOR]

[Display omitted] • Titanium species coordinated with –NH 2 group and oxygen-donor in AUiO-66(Zr/Ti)-4h. • The ligand-to-linker metal charge transfer mechanism occurred in AUiO-66(Zr/Ti)-4h. • AUiO-66(Zr/Ti)-4h showed superior photoactivity and stability under visible light. • Both benzoic acid and maleic anhydride are the key species on AUiO-66(Zr/Ti)-4h. • Both toluene/H 2 O activation and charge mobility are critical in toluene oxidation. Photocatalytic oxidation (PCO) of volatile organic compounds (VOCs) over MOF-based photocatalysts is considerably impeded by the weak activation of reactant molecules on the catalyst surface and low charge carrier mobility. In this study, we demonstrate that atomically dispersed Ti species anchored on NH 2 -UiO-66(Zr) (AUiO-66(Zr/Ti)) exhibit high visible-light-responsive photocatalytic activity toward toluene vapor with an 83 % removal efficiency and 89 % CO 2 selectivity. These results are markedly superior to those reported in the literature. More importantly, AUiO-66(Zr/Ti) exhibited excellent catalytic stability during a prolonged reaction, while its pristine AUiO-66(Zr) counterpart underwent rapid catalytic deactivation after a few hours. The optimized sample, AUiO-66(Zr/Ti)-4h, provided extended visible light absorption and enhanced charge carrier mobility due to ligand-to-linker metal charge transfer. Meanwhile, the defect-rich surface of AUiO-66(Zr/Ti)-4h facilitated the activation of H 2 O/toluene molecules into the critical intermediates of hydroxyl, benzoic acid, and maleic anhydride, which were effectively converted under visible light illumination. On the basis of the combined results of the PCO of toluene and material characterization, the structure − activity relationship and the related catalytic mechanism are discussed comprehensively. [ABSTRACT FROM AUTHOR]

• The OD-ZnO/C composites were engineered with defect-rich and defect-poor surfaces. • The OD-ZnO/C-N 2 -600 exhibited a high quantum yield of 0.13% under Vis-NIR. • The OD-ZnO/C-N 2 -600 showed superior stability compared to OD-ZnO/C-Air-500. • Both CO 2 – and HCOO– are the key intermediates on the surface of OD-ZnO/C-N 2 -600. • Both CO 2 activation and charge carrier mobility are critical in CO 2 photoreduction. Photocatalytic CO 2 reduction with H 2 O over wide bandgap semiconductor-based photocatalysts is significantly limited by the low light utilization efficiency and poor activation of CO 2 /H 2 O molecules on the photocatalyst's surface. Herein, we demonstrate that oxygen-deficient ZnO/carbon dot (OD-ZnO/C) hybrid, rationally engineered with synergistically enhanced CO 2 /H 2 O activation ability and increased light utilization efficiency, showed excellent full spectrum (UV, visible and NIR light)-driven CO 2 photoreduction. Under UV–Vis-NIR, Vis-NIR and NIR light separately, the optimized sample demonstrated high quantum yields of 0.26%, 0.13% and 0.05% for CO production, yields which are considerably superior to the reported values in the literature. The synergistic effects between OD-ZnO and carbon dots for visible- and NIR-driven CO 2 reduction were systematically investigated. Experimental results showed that both the defect-induced sub-band in OD-ZnO and the upconverting emission from the carbon dots effectively increased the light utilization efficiency within the UV–Vis to NIR region, and the heterojunctions formed between OD-ZnO and carbon dots promoted the efficient separation of charge carriers. Meanwhile, the defect-rich surface ensures the efficient adsorption and activation of CO 2 /H 2 O into the key intermediate CO 2 –, formate, and hydroxyl species, which are effectively converted under light illumination from UV–Vis to NIR region. Based on the combined results of the CO 2 photoreduction analysis and the material characterization, plausible CO 2 photoreduction pathways under visible and NIR light irradiation are proposed. [ABSTRACT FROM AUTHOR]

For the simultaneous identification (SI) problem on the moving vehicle loads and bridge damage, the existing methods fail to appropriately consider the sparse characteristics of structural damage and ignore the prior information of vehicle loads, which make them suffering from challenges such as prolonged computation cost, poor noise robustness, and limited identification accuracy. To address this issue, a novel semi-convex function is proposed to construct a theoretical framework for the SI problem using the bridge dynamic responses subjected to moving vehicles in this study. Firstly, the bridge damage-induced virtual forces are conceptualized as a new form of moving residual forces characterized by block sparsity properties, and the damage location is then determined by the frequency characteristics with the largest fundamental frequency amplitude of moving residual forces. Secondly, a semi-convex function model encompassing moving forces and moving residual forces is defined. Combined with sparse regularization strategy, an improved alternating direction method of multipliers algorithm is proposed and applied to simultaneously solve for both moving vehicle loads and damage degrees. To assess the effectiveness and feasibility of the proposed method, extensive numerical validations are conducted in various bridge damage scenarios. Additionally, a series of truss bridge experiments are performed in laboratory under multiple damage and vehicle axle-weight conditions. The results show that compared with the existing outstanding methods, the proposed semi-convex function method can significantly reduce the identification cost, enhance robustness to noise, and demonstrate notable improvements in accuracy for the SI problem, which provides an innovative and more efficient solution to the SI problem in bridge engineering. [ABSTRACT FROM AUTHOR]

Hemin/CNT/Ti 3 C 2 T x hybrid with redox catalytic ability for electrochemical determination of H 2 O 2 and UA. [Display omitted] Herein, a functional hybrid named metalloporphyrin hemin modified carbon nanotube decorated titanium carbide (Hemin/CNT/Ti 3 C 2 T x) with redox catalytic ability is studied and applied to electrochemical sensing. The morphology, crystal structure and chemical composition of the hybrid are investigated through field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), X-ray diffractometer (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) analysis. Benefiting from the unique multilayer structure, strong enrichment ability, excellent electrochemical performance of CNT/Ti 3 C 2 T x and outstanding catalytic property of hemin, the developed Hemin/CNT/Ti 3 C 2 T x hybrid presents desirable performance for electrochemical sensing. Two independent electrochemical sensing techniques including chronoamperometry (i-t) and differential pulse voltammetry (DPV) are adopted to realize hydrogen peroxide (H 2 O 2) and uric acid (UA) determination, demonstrating the excellent redox catalytic ability of Hemin/CNT/Ti 3 C 2 T x. More importantly, it is successfully applied to real-time monitoring of H 2 O 2 released from living cells, and accurate determination of UA in urine samples is also realized, demonstrating a good practicability. [ABSTRACT FROM AUTHOR]

Hemin/CNT/Ti 3 C 2 T x hybrid with redox catalytic ability for electrochemical determination of H 2 O 2 and UA. [Display omitted] Herein, a functional hybrid named metalloporphyrin hemin modified carbon nanotube decorated titanium carbide (Hemin/CNT/Ti 3 C 2 T x) with redox catalytic ability is studied and applied to electrochemical sensing. The morphology, crystal structure and chemical composition of the hybrid are investigated through field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), X-ray diffractometer (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) analysis. Benefiting from the unique multilayer structure, strong enrichment ability, excellent electrochemical performance of CNT/Ti 3 C 2 T x and outstanding catalytic property of hemin, the developed Hemin/CNT/Ti 3 C 2 T x hybrid presents desirable performance for electrochemical sensing. Two independent electrochemical sensing techniques including chronoamperometry (i-t) and differential pulse voltammetry (DPV) are adopted to realize hydrogen peroxide (H 2 O 2) and uric acid (UA) determination, demonstrating the excellent redox catalytic ability of Hemin/CNT/Ti 3 C 2 T x. More importantly, it is successfully applied to real-time monitoring of H 2 O 2 released from living cells, and accurate determination of UA in urine samples is also realized, demonstrating a good practicability. [ABSTRACT FROM AUTHOR]

Abstract: A fiber optic sensor array which is structured by four Sagnac fiber optic sensors is proposed to detect and locate a simulative source of acoustic emission (AE). The sensing loops of Sagnac interferometer (SI) are regarded as point sensors as their small size. Based on the derived output light intensity expression of SI, the optimum work condition of the Sagnac fiber optic sensor is discussed through the simulation of MATLAB. Four sensors are respectively placed on a steel plate to structure the sensor array and the location algorithms are expatiated. When an impact is generated by an artificial AE source at any position of the plate, the AE signal will be detected by four sensors at different times. With the help of a single chip microcomputer (SCM) which can calculate the position of the AE source and display it on LED, we have implemented an intelligent detection and location. [Copyright &y& Elsevier]

Abstract: Autoregulation capacity has been classically assessed with a ‘two-point’ measurement or static autoregulation (sAR). In such an approach, stabilized hemodynamic parameters are determined before and after a perfusion pressure challenge. Analysis of dynamic autoregulation (dAR), an early phase of blood flow response to a sudden perfusion pressure change is emerging as a preferred approach to assess the capacity of autoregulation in many non-ocular tissues and has developed rapidly in the last decade. The purpose of this study was to develop a method to quantify dAR in the optic nerve head (ONH). In six pentobarbital (6–9 mg/kg/h, IV) anesthetized rhesus monkeys, dAR was elicited by increasing intraocular pressure (IOP) from 10 to 30 or 40 mmHg (IOP10–30/IOP10–40) manometrically via switch between reservoirs connected to the anterior chamber. Relative blood flow changes during dAR in the ONH, estimated with a laser speckle flowgraph (LSFG), were continuously measured for 1 min. Time-domain parameters of dAR response, including: BFΔmax (maximal blood flow decrease, %), Kr (descending slope of blood flow from baseline to BFΔmax ) and Tr (descending time of blood flow from baseline to BFΔmax ) were extracted and analyzed offline. For each monkey, same procedure was repeated three times during three different visits. The test-retest repeatability and inter-ocular difference of the parameters was statistically evaluated. During IOP10–30 and IOP10–40, the mean arterial BP was 89 ± 7 and 85 ± 6 mmHg, respectively. Immediately after the reservoir was switched, the blood flow started to decline and reached maximal in ∼4 s. The blood flow then returned back toward baseline despite continuous IOP increase, which took 8–11 s to reach the level of the raised reservoir. The general pattern of blood flow responses was similar between IOP10–30 and IOP10–40 and there was no statistically significant difference for Tr (P > 0.05). However, IOP10–40 caused greater BFΔmax and deeper Kr than IOP10–30 (P < 0.0001 and P < 0.05, respectively). The blood flow during steady state, 5 min after IOP elevation, showed no statistically significant difference from baseline (P > 0.05). All dAR parameters (Tr , Kr and BFΔmax ) showed no significant difference across the 3 visits (Repeat measures ANOVA, P = 0.7, 0.2 and 0.2, respectively); the corresponding coefficients of variance were 24%, 43% and 34% during IOP10–30 and 11.8%, 30.3% and 19.0% during IOP10–40. The mean dAR parameters between the eyes showed no statistically differences (P = 0.6) during both IOP10–30 and IOP10–40. The current study showed that a rapid ocular perfusion pressure decrease induced by a sudden IOP step increase evoked a transient and reproducible dAR response in the ONH of non-human primates measured with LSFG. Quantitative analysis of dAR may provide a direct view of vasomotorial activity in the resistant vessels and thus a new approach to assess the autoregulatory capacity in the ONH. [Copyright &y& Elsevier]

Abstract: Agrocybe aegerita lectin (AAL) was identified previously in our group as a novel galectin from medicinal fungi Agrocybe aegerita, and has been shown to effectively induce cancer cell cycle arrest and apoptosis in vitro and tumor regression in vivo. Here, AAL was observed to translocate into the HeLa cell nucleus and induce cell apoptosis when it was predominantly in the nucleus. The N-terminus and C-terminus of AAL were required for nuclear localization. Site mutated proteins were generated based on AAL structure. Dimer interface mutant I25G, carbohydrate recognition domain (CRD) mutant R63H, and loop region mutant L33A could not enter the nucleus and lost the ability to induce apoptosis. CRD mutant H59Q and loop region mutant I144G maintained nuclear localization activity, and H59Q retained residual bioability but I144G had no activity, indicating that nuclear localization is important but not sufficient for AAL to become apoptotically active. Our findings provide a novel antitumor mechanism of fungal galectin. [Copyright &y& Elsevier]

The nuclear matrix-associated protein Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU), also known as SAF-A, is known to maintain active chromatin structure in mouse hepatocytes. However, the functional roles and molecular mechanisms of HNRNPU in the development of hepatocellular carcinoma (HCC) remain largely unknown. Herein, we found that HNRNPU was upregulated in HCC, and the proliferation of HCC cells was inhibited in vitro and in vivo upon HNRNPU knockdown. Moreover, the upregulation of HNRNPU was correlated with poor prognosis in HCC. Mechanistically, HNRNPU bound to the CDK2 gene locus, a key factor in cell cycle regulation, where it was enriched with H3K27 acetylation (H3K27ac), H3K9 acetylation (H3K9ac), and H3K4 mono-methylation (H3K4me1). Furthermore, HNRNPU knockdown reduced the levels of H3K27ac and H3K9ac at the binding site, where the levels of H3K27 tri-methylation (H3K27me3) were increased, eventually leading to the downregulation of CDK2. Collectively, our results provide a new mechanism whereby HNRNPU promotes HCC development by enhancing the transcription of CDK2. • The expression of HNRNPU is upregulated in hepatocellular carcinoma. • HNRNPU knockdown significantly inhibits HCC cell proliferation. • HNRNPU knockdown induces cell cycle arrest. • HNRNPU regulates CDK2 transcription by directly binding to the CDK2 gene locus. [ABSTRACT FROM AUTHOR]

• 119 active components in GXV and 169 potential targets shared between GXV and VR were identified. • GXV produces marked anti-apoptosis and anti-fibrosis effects in VR though Caspase-3 and TGF-β1. • Our study deepens the understanding of the molecular mechanisms of GXV in treating VR. Guanxin V (GXV) has been widely used to treat ventricular remodeling (VR) in clinical practice in China. However, the underlying mechanisms are currently still lack. A systematic pharmacology-based strategy was utilized for predicting the synergistic pharmacological mechanisms of GXV in VR. The active compounds of GXV were selected and then the potential targets of these compounds contained in GXV and VR were successively identified. Then, after networks were constructed, DAVID was applied to functional enrichment. Moreover, the key findings were validated though molecular docking and molecular biology experiments. A total of 119 active components in GXV and 169 potential targets shared between GXV and VR were obtained. The results of functional enrichment indicated that several biological processes and signaling pathways, mainly cell apoptosis and fibrosis. Finally, we discovered GXV produced marked anti-apoptosis and anti-fibrosis effects in VR though Caspase-3 and TGF-β1. GXV could relieve and reverse VR through anti-apoptosis and anti-fibrosis effects predicted by systematic pharmacology and validated by molecular docking and molecular experiments. Our study deepens the understanding of the molecular mechanisms of GXV in treating VR. [ABSTRACT FROM AUTHOR]

Abstract: We previously identified a novel centrosomal protein CPAP, which carries a 112-residue motif that is essential for microtubule destabilization. In this report, we define both the microtubule (MT) binding and destabilizing domains in human CPAP and analyze the mutations that affect its MT-destabilizing activity. Analysis of a series of CPAP truncated proteins showed that the MT-binding domain (MBD; residues 423–607) of CPAP is located next to its MT-destabilizing domain (MDD; residues 311–422). Site-specific mutagenesis revealed that the mutations that either disrupt the α-helical structure (Y341P, I346P, L348P, and triple-P) or alter the charge property (KR377EE) of the MDD significantly affect its MT-destabilizing ability. The activity for binding to a tubulin heterodimer was also significantly reduced in KR377EE mutant. Furthermore, we have analyzed the putative function of Drosophila d-SAS-4, a distant relative of human CPAP, which shares a conserved ∼20-aa sequence with the MDD of CPAP. Our results show that mutations in this conserved sequence also eliminate d-SAS-4′s MT-destabilizing activity, suggesting that d-SAS-4 and CPAP may play similar roles within cells. [Copyright &y& Elsevier]

Let E be a metric space. We introduce a notion of connectedness index of E , which is the Hausdorff dimension of the union of non-trivial connected components of E. We show that the connectedness index of a fractal cube E is strictly less than the Hausdorff dimension of E provided that E possesses a trivial connected component. Hence the connectedness index is a new Lipschitz invariant. Moreover, we investigate the relation between the connectedness index and topological Hausdorff dimension. [ABSTRACT FROM AUTHOR]

Cellular vesicle long-distance transport along the cytoplasmic actin network has recently been uncovered in several cell systems. In metaphase mouse oocytes, the motor protein myosin-5b (Myo5b) and the actin nucleation factor Spire are recruited to the Rab11a-positive vesicle membrane, forming a ternary complex of Myo5b/Spire/Rab11a that drives the vesicle long-distance transport to the oocyte cortex. However, the mechanism underlying the intermolecular regulation of the Myo5b/Spire/Rab11a complex remains unknown. In this study, we expressed and purified Myo5b, Spire2, and Rab11a proteins, and performed ATPase activity measurements, pulldown and single-molecule motility assays. Our results demonstrate that both Spire2 and Rab11a are required to activate Myo5b motor activity under physiological ionic conditions. The GTBM fragment of Spire2 stimulates the ATPase activity of Myo5b, while Rab11a enhances this activation. This activation occurs by disrupting the head-tail interaction of Myo5b. Furthermore, at the single-molecule level, we observed that the GTBM fragment of Spire2 and Rab11a coordinate to stimulate the Myo5b motility activity. Based on our results, we propose that upon association with the vesicle membrane, Myo5b, Spire2 and Rab11a form a ternary complex, and the inhibited Myo5b is synergistically activated by Spire2 and Rab11a, thereby triggering the long-distance transport of vesicles. • Both Spire2 and Rab11a are required for the activation of Myosin-5b ATPase activity. • This activation by Spire2 and Rab11a occurs by disrupting the head-tail interaction of Myosin-5b. • Spire2 and Rab11a coordinates to stimulate Myosin-5b single-molecular motility activity. [ABSTRACT FROM AUTHOR]

[Display omitted] Electrospinning is an effective technique to fabricate one-dimensional materials. In this study, cobalt-embedded carbon nanofibers (Co@CNFs) are obtained via carbonization of electrospun cobalt Prussian blue analogue (Co-Co PBA) under nitrogen atmosphere. The Co@CNFs have metallic cobalt surrounded by graphitic carbon shells and possess high specific surface area, rich porosity, high graphitic degree, and rational nitrogen doping. The structure merits endow them with excellent electrocatalytic performances for oxygen reduction reaction (ORR): an onset potential of 0.867 V vs. RHE and 0.784 V vs. RHE at j = − 3 mA cm−2 with a four-electron transfer process. Through a further mild oxidation process, we obtain Co 3 O 4 nanoparticles-embedded nitrogen-doped carbon (Co 3 O 4 @CNFs) with spindle-like morphology. When working as the anode materials for lithium-ion batteries (LIBs), Co 3 O 4 @CNFs show high specific capacity, good stability, and excellent rate capability. The Co 3 O 4 @CNFs anode delivers a discharge specific capacity of 1404 mA h g−1 after 100 cycles at a current density of 100 mA g−1 and about 500 mA h g−1 after 500 cycles at 2000 mA g−1. The diffusion- and capacitive-controlled processes both contribute to the charge storage of the Co 3 O 4 @CNFs electrode. This study provides a new strategy to fabricate the excellent electrocatalysts for ORR and anode materials for LIBs via facile electrospinning. [ABSTRACT FROM AUTHOR]

Abstract Colorectal cancer (CRC) is a major health problem due to its high mortality rate. The incidence of CRC is increasing in young individuals. Oxaliplatin (OXA) is an approved third-generation drug and is used for first-line chemotherapy in CRC. Although current standard chemotherapy improves the overall survival of CRC patients, an increasing number of reports of OXA resistance in CRC therapy indicates that resistance has become an urgent problem in clinical applications. Dicer is a critical enzyme involved in miRNA maturation. The expression of Dicer has been reported to be involved in the resistance to various drugs in cancer. In the present study, we aimed to investigate the role of Dicer in OXA resistance in CRC. We found that OXA treatment inhibited Dicer expression through decreasing the protein stability. OXA-induced Dicer protein degradation occurred through both proteasomal and lysosomal proteolysis, while the CHIP E3 ligase was involved in OXA-mediated Dicer ubiquitination and degradation. We established stable OXA-resistant clones from CRC cells, and observed that the CHIP E3 ligase was decreased, along with the increased Dicer expression in OXA-resistant cells. Knockdown of Dicer resensitized CRC cells to OXA treatment. In this study, we have revealed the role of miRNA biogenesis factors in OXA resistance in CRC cells. Highlights • Oxaliplatin treatment decreases Dicer protein stability. • Oxaliplatin induces Dicer ubiquitination for protein degradation. • Upregulation of Dicer enhances oxaliplatin resistance in colon cancer cells. • Inhibition of Dicer restores the sensitivity of colon cancer cells to oxaliplatin. [ABSTRACT FROM AUTHOR]

Leukocyte-derived chemotaxin-2 (LECT2) is a multifunctional immunoregulator that plays several pivotal roles in the host's defense against pathogens. This study aimed to elucidate the specific functions and mechanisms of LECT2 (CaLECT2) in the northern snakehead (Channa argus) during infections with pathogens such as Nocardia seriolae (N. seriolae). We identified CaLECT2 in the northern snakehead, demonstrating its participation in the immune response to N. seriolae infection. CaLECT2 contains an open reading frame (ORF) of 459 bp, encoding a peptide of 152 amino acids featuring a conserved peptidase M23 domain. The CaLECT2 protein shares 62%–84 % identities with proteins from various other fish species. Transcriptional expression analysis revealed that CaLECT2 was constitutively expressed in all examined tissues, with the highest expression observed in the liver. Following intraperitoneal infection with N. seriolae , CaLECT2 transcription increased in the spleen, trunk kidney, and liver. In vivo challenge experiments showed that injecting recombinant CaLECT2 (rCaLECT2) could protect the snakehead against N. seriolae infection by reducing bacterial load, enhancing serum antibacterial activity and antioxidant capacity, and minimizing tissue damage. Moreover, in vitro analysis indicated that rCaLECT2 significantly enhanced the migration, respiratory burst, and microbicidal activity of the head kidney-derived phagocytes. These findings provide new insights into the role of LECT2 in the antibacterial immunity of fish. • CaLECT2 is upregulated in northern snakehead challenged by N. seriolae. • RCaLECT2 enhanced bacterial killing and respiratory burst in phagocytes of northern snakehead. • Intraperitoneal injection of rCaLECT2 reduced the bacterial burden of northern snakehead infected with N. seriolae. • Intraperitoneal injection of rCaLECT2 improved the survival rate of northern snakehead infected with N. seriolae. [ABSTRACT FROM AUTHOR]

Highlights: [•] A method was applied to evaluate mechanisms. [•] Twenty-six phytochemical components and 46 target proteins were selected. [•] Compound–protein interaction probability was calculated using PreDPI-Ki. [•] A visualized heat map and network were constructed. [•] Mechanisms could be divided using principal components analysis. [Copyright &y& Elsevier]

Abstract: The refolding kinetics of the reduced, denatured hen egg white lysozyme in sodium bis(2-ethylhexyl)sulfosuccinate (AOT)–isooctane–water reverse micelles at different water-to-surfactant molar ratios has been investigated by fluorescence spectroscopy and UV spectroscopy. The oxidative refolding of the confined lysozyme is biphasic in AOT reverse micelles. When the water-to-surfactant molar ratio () is 12.6, the relative activity of encapsulated lysozyme after refolding for 24 h in AOT reverse micelles increases 46% compared with that in bulk water. Furthermore, aggregation of lysozyme at a higher concentration (0.2 mM) in AOT reverse micelles at of 6.3 or 12.6 is not observed; in contrast, the oxidative refolding of lysozyme in bulk water must be at a lower protein concentration (5 μM) in order to avoid a serious aggregation of the protein. For comparison, we have also investigated the effect of AOT on lysozyme activity and found that the residual activity of lysozyme decreases with increasing the concentration of AOT from 1 to 5 mM. When AOT concentration is larger than 2 mM, lysozyme is almost completely inactivated by AOT and most of lysozyme activity is lost. Together, our data demonstrate that AOT reverse micelles with suitable water-to-surfactant molar ratios are favorable to the oxidative refolding of reduced, denatured lysozyme at a higher concentration, compared with bulk water. [Copyright &y& Elsevier]

Abstract: A novel simplified method for synthesis of surface-enhanced Raman scattering tags has been reported. This synthesis method is based on reverse micelle technique using Igepal CO-520 as a surfactant and the mixed solution of silver nitrate and rhodamine dyes with isothiocyanate group as water pool followed by hydrazine hydrate reduction and TEOS polymerization leading to the formation of silica layer surrounding the silver core. Compared to the method reported in literature, the proposed methodology eliminates the necessity of vitrophilic pretreatment and makes it possible to complete all different processes including the preparation of silver nanoparticles, the conjugation of dye molecules and the formation of silica shell in the microreactor. The nanoparticle-based surface-enhanced Raman tags obtained are composed of silver core conjugated with rhodamine dyes and an encasing silica shell. Both the dyes themselves and the Ag/SiO2 core–shell nanoparticles without the encapsulation of dyes exhibit no Raman signals. However, the Ag/SiO2 core–shell nanoparticles exhibit strong Raman signals when encapsulated with these dyes. This is due to the appearance of fluorescence quenching and surface-enhanced Raman scattering effect resulting from the conjugation of dyes and silver core. The Raman tags were characterized using transmission electron microscopy (TEM), UV–visible absorption spectrometry, and Raman spectrometry. [Copyright &y& Elsevier]

Abstract: The spontaneously hypertensive rat (SHR) is a model of human insulin resistance syndrome. Quantitative trait loci for cellular defects in glucose and fatty acid metabolism have been mapped to an overlapping region of rat chromosome (RNO) RNO4 in SHR of the National Institute of Health colony, where a deletion in the Cd36 gene has been implicated as the causative mutation of insulin resistance. The present study has examined the potential presence of RNO4 linkage to a series of metabolic phenotypes in F2 progeny derived from SHR of a Japanese colony (SHR/Izm) without the Cd36 mutation. Our data demonstrate that ‘major’ insulin resistance gene(s) are unlikely to exist on RNO4 in SHR/Izm and in vitro phenotypes measured in isolated adipocytes do not cosegregate in the F2 population studied. Thus, it seems to be difficult to explain the underlying genetic mechanisms of insulin resistance by a single major gene on RNO4. [Copyright &y& Elsevier]

Cells have evolved molecular chaperones that modulate phase separation and misfolding of amyloidogenic proteins to prevent neurodegenerative diseases. Protein disulfide isomerase (PDI), mainly located at the endoplasmic reticulum and also present in the cytosol, acts as both an enzyme and a molecular chaperone. PDI is observed to be S-nitrosylated in the brain of Alzheimer's disease patients, but the mechanism has remained elusive. We herein report that both wild-type PDI and its quadruple cysteine mutant only having chaperone activity, significantly inhibit pathological phosphorylation and abnormal aggregation of Tau in cells, and significantly decrease the mitochondrial damage and Tau cytotoxicity resulting from Tau aberrant aggregation, highlighting the chaperone property of PDI. More importantly, we show that wild-type PDI is selectively recruited by liquid droplets of Tau, which significantly inhibits phase separation and stress granule formation of Tau, whereas S-nitrosylation of PDI abrogates the recruitment and inhibition. These findings demonstrate how phase separation of Tau is physiologically regulated by PDI and how S-nitrosylation of PDI, a perturbation in this regulation, leads to disease. Image 1 • Chaperones are recruited to Tau droplets to inhibit Tau accumulation in the droplets. • Recruitment of chaperones alters the dynamic properties of Tau phase-separated droplets. • S-nitrosylation of PDI abrogates its ability to recognize targeted proteins physically. • S-nitrosylation of PDI abrogates its ability to inhibit the phase separation of Tau. [ABSTRACT FROM AUTHOR]

Prion diseases, such as Creutzfeldt–Jakob disease and bovine spongiform encephalopathy, are fatal neurodegenerative diseases that affect many mammals including humans and are caused by the misfolding of prion protein (PrP). A naturally occurring protective polymorphism G127V in human PrP has recently been found to significantly attenuate prion diseases, but the mechanism has remained elusive. We herein report that the hydrophobic chain introduced in G127V significantly inhibits amyloid fibril formation by human PrP, highlighting the protective effect of the G127V polymorphism. We further introduce an amino acid with a different hydrophobic chain (Ile) at the same position and find that G127I has similar protective effects as G127V. Moreover, we show that these two neutralizing mutations, G127V and G127I, significantly decrease the human PrP cytotoxicity resulting from PrP fibril formation, mitochondrial damage, and elevated reactive oxygen species production enhanced by a strong prion-prone peptide PrP 106-126. These findings elucidate the molecular basis for a natural protective polymorphism in PrP and will enable the development of novel therapeutic strategies against prion diseases. Image 1 • Neutralizing mutations modulate the liquid-liquid phase separation of the normal cellular prion proteinPrP. • Neutralizing mutations significantly inhibit the fibrillization of prion protein (PrP). • Neutralizing mutations protect against mitochondrial damage in cells. • Neutralizing mutations decrease reactive oxygen species production and cytotoxicity of PrP. [ABSTRACT FROM AUTHOR]

Here, we have demonstrated an innovative decontamination strategy using molten salts as a solvent to clean stubborn uranium contaminants on stainless steel surfaces. The aim of this work was to investigate the evolutionary path of contaminants in molten salts to reveal the decontamination mechanism, thus providing a basis for the practical application of the method. Thermodynamic analysis revealed that alkali metal hydroxides, carbonates, chlorides and nitrates can react with uranium oxides (UO 3 and U 3 O 8) to form various uranates. Notably, the decontamination mechanism was elucidated by analyzing the chemical composition of the contaminants in the molten salts and the surface morphology of the specimens considering NaOH–Na 2 CO 3 –NaCl melt as the decontaminant. The decontamination process involved two stages: a rapid decontamination stage dominated by the thermal effect of molten salt, and a stable decontamination stage governed by the chemical reactions and diffusion of molten salt. Subsequently, a multiple decontamination strategy was implemented to achieve high decontamination rates and low residual radioactivity. Within the actual cleaning time of 30 min, the decontamination efficiency (DE) of UO 3 -contaminated specimens reached 97.8% and 93.0% for U 3 O 8 -contaminated specimens. Simultaneously, the radioactivity levels of all specimens were reduced to below the control level for reuse in the nuclear domain. Particularly, the actual radioactive waste from the nuclear industry reached a reusable level of radioactivity after decontamination. The NaOH–Na 2 CO 3 –NaCl melt outperforms conventional chemical solvents and may be one of the most rapid and efficient decontaminants for stubborn uranium contamination of metal surfaces, which provides insights in regard to handling nuclear waste. [Display omitted] • Molten salts provided efficient and rapid removal of radioactive contamination. • The first reported mechanism of uranium contaminant removal by molten salts. • Highly reactive molten salts can form uranates with uranium contaminants. • The decontaminated specimens can be reused in the nuclear industry. [ABSTRACT FROM AUTHOR]

Abstract Although parallel alignment of fibroblasts to the tension lines of scar has been evidenced in vivo, how scar contracture generates directional contraction remains largely unclear due to the lack of effective in vitro model. Fibroblast populated collagen lattice (FPCL), a widely used in vitro model, fails to mimic scar contracture since it produces concentric contraction with the random orientation of fibroblast. We hypothesized that a novel FPCL model with fibroblast alignment might produce directional contraction and then simulate scar contracture better. Here, we showed that although direct current electric fields (DCEFs) enabled fibroblasts aligned perpendicularly to the field vector, it also promoted electrotactic migration of fibroblast in FPCL. By contrast, biphasic pulse direct current electric fields (BPDCEFs), featured by reversal of the EF direction periodically, abolished the electrotactic migration, but induced fibroblast alignment in a pulse frequency dependent manner. Specifically, BPDCEF at a pulse frequency of 0.0002 Hz induced fibroblast alignment comparable to that induced by DCEF under the same field strength (300 mV/mm), leading to an enhanced contraction of FPCL along the direction of cell alignment. FPCL pretreated by BPDCEF showed an elliptical contraction whereas it was concentric in control FPCL. Further study revealed that F-actin redistributions acted as a key mechanism for the induction of fibroblasts alignment by BPDCEF. Cytochalasin D, an inhibitor of actin dynamics, abolished F-actins redistribution, and significantly suppressed the fibroblasts alignment and the directional contraction of FPCL. Importantly, BPDCEF significantly increased RhoA activity in fibroblasts, while this response was attenuated by C3 transferase pre-treatment, a potent inhibitor of RhoA, caused F-actin depolymerization and actin filament bundle randomly distributed. Taken together, our study suggests a crucial role for fibroblast orientation in scar contracture, and provides a novel FPCL model that may be feasible and effective for investigating scar contracture in vitro. [ABSTRACT FROM AUTHOR]

Cerebrovascular aging has a high relationship with stroke and neurodegenerative disease. In the present study, we evaluated the influence of fibroblast growth factor 21 (FGF21) on angiotensin (Ang II)-mediated cerebrovascular aging in human brain vascular smooth muscle cells (hBVSMCs). Ang II induced remarkable aging-phenotypes in hBVSMCs, including enhanced SA-β-gal staining and NBS1 protein expression. First, we used immunoblotting assay to confirm protein expression of FGF21 receptor (FGFR1) and the co-receptor β-Klotho in cultured hBVSMCs. Second, we found that FGF21 treatment partly prevented the aging-related changes induced by Ang II. FGF21 inhibited Ang II-enhanced ROS production/superoxide anion levels, rescued the Ang II-reduced Complex IV and citrate synthase activities, and suppressed the Ang II-induced meprin protein expression. Third, we showed that FGF21 not only inhibited the Ang II-induced p53 activation, but also blocked the action of Ang II on Siah-1-TRF signaling pathway which is upstream factors for p53 activation. At last, either chemical inhibition of AMPK signaling pathway by a specific antagonist Compound C or knockdown of AMPKα1/2 isoform using siRNA, successfully abolished the anti-aging action of FGF21 in hBVSMCs. These results indicate that FGF21 protects against Ang II-induced cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 activation in an AMPK-dependent manner, and highlight the therapeutic value of FGF21 in cerebrovascular aging-related diseases such as stroke and neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Renal interstitial fibrosis closely relates to chronic kidney disease and is regarded as the final common pathway in most cases of end-stage renal disease. Metabolomic biomarkers can facilitate early diagnosis and allow better understanding of the pathogenesis underlying renal fibrosis. Gas chromatography–mass spectrometry (GC/MS) is one of the most promising techniques for identification of metabolites. However, the existence of the background, baseline offset, and overlapping peaks makes accurate identification of the metabolites unachievable. In this study, GC/MS coupled with chemometric methods was successfully developed to accurately identify and seek metabolic biomarkers for rats with renal fibrosis. By using these methods, seventy-six metabolites from rat serum were accurately identified and five metabolites (i.e., urea, ornithine, citric acid, galactose, and cholesterol) may be useful as potential biomarkers for renal fibrosis [ABSTRACT FROM AUTHOR]

Northern snakehead (Channa argus) is an indigenous fish species and is one of popularly cultured snakeheads in China and other Asian countries. Unfortunately, Nocardia seriolae infections have caused considerable losses in the snakehead aquaculture industry. However, the infectivity and the immune response induced by N. seriolae in snakehead are unclear. In order to better understand the immune response of Northern snakehead in a series of time points after N. seriolae challenge, we conducted the transcriptomic comparison in snakehead spleen at 48, 96, and 144 h after the challenge of N. seriola against their control counterparts. Gene annotation and pathway analysis of differentially expressed genes (DEGs) were carried out to understand the functions of the DEGs. Additionally, protein-protein interaction networks were conducted to obtain the interaction relationships of immune-related DEGs. These results revealed the expression changes of multiple DEGs and signaling pathways involved in immunity during N. seriolae infection, which will facilitate our comprehensive understanding of the mechanisms involved in the immune response to bacterial infection in the northern snakehead. • Channa argus spleen transcriptome was sequenced following infection with Nocardia. seriolae. • Consistently expressed proteins were analyzed by protein-protein network analysis. • KEGG analysis based on time-series revealed 29 potential pathways in spleen. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a devastating mental illness with high morbidity and major social and economic burden. Currently, there is no promising therapy available for the treatment of PTSD. Some clinical studies showed that ketamine could effectively alleviate PTSD symptoms. However, it is still unclear which brain region ketamine targets and how it attenuates the PTSD-like effects. In this study, we examined the effect of ketamine on fear generalization (a core symptom of PTSD) by using a mice model of fear generalization induced by fear conditioning procedure. Before retrieval, ketamine was locally infused into the nucleus accumbens (a brain region closely associated with PTSD). Fear generalization mice were subjected to behavioral testing and biochemical assessments, following ketamine infusion. The results showed that the foot shock strength-dependently induced fear generalization in mice with increased c-fos activity, and a lower level of GluR1(S845), GluR1(S831) protein, and a higher level of P-GluN2B protein in the nucleus accumbens (NAc). Local infusion of ketamine into NAc decreased the fear generalization together with an increased level of GluR1(S845), GluR1(S831) protein, and decreased level of P-GluN2B protein. Altogether, these results conclude that ketamine might affect the glutamatergic signaling in the NAc to attenuate the fear generalization in mice. • The foot-shock stress strength-dependently induced fear generalization in mice. • Fear generalized mice showed an impairment of glutamatergic signaling in the nucleus accumbens. • Local infusion of ketamine into NAc decreased the fear generalization. • Fear generalization-induced alteration in P-GluN2B and P-GluR1 in NAc is reversed by ketamine. [ABSTRACT FROM AUTHOR]

Highlights: [•] FOXO1 and resistin mRNA levels are higher in differentiating preadipocytes than those in non-differentiating preadipocytes. [•] FOXO1 activates resistin promoter activity in preadipocytes and adipocytes. [•] FOXO1 activation of resistin promoter depends on the phosphorylation and dephosphorylation of FOXO1. [ABSTRACT FROM AUTHOR]

Abstract: Endothelin (ET)-1 and suppressor of cytokine signaling (SOCS)-3 were respectively found to regulate energy metabolism and hormone signaling in fat cells. Although ET-1 can also regulate the expression of SOCS-3-stimulating hormones, it is still unknown whether ET-1 regulates SOCS-3 gene expression. This study investigated the pathways involved in ET-1’s modulation of SOCS-3 gene expression in 3T3-L1 adipocytes. ET-1 upregulated SOCS-3 mRNA and protein expression in dose- and time-dependent manners. The concentration of ET-1 that increased SOCS-3 mRNA levels by 250–400% was ∼100nM with 2–4h of treatment. Treatment with actinomycin D prevented ET-1-stimulated SOCS-3 mRNA expression, suggesting that the effect of ET-1 requires new mRNA synthesis. Pretreatment with the ET type A receptor (ETAR) antagonist, BQ-610, but not the ET type B receptor (ETBR) antagonist, BQ-788, prevented the stimulatory effect of ET-1 on SOCS-3 gene expression. The specific inhibitors of either MEK1 (U-0126 and PD-98059), JAK (AG-490), JNK (SP-600125), or PI3K (LY-294002 and wortmannin) reduced ET-1-increased levels of SOCS-3 mRNA and respectively inhibited ET-1-stimulated activities of MEK1, JAK, JNK, and PI3K. These results imply that the ETAR, ERK, JAK, JNK, and PI3K are functionally necessary for ET-1’s stimulation of SOCS-3 gene expression. Moreover, ET-1 was observed to upregulate expressions of SOCS-1, -2, -3, -4, -5, and -6 mRNAs, but not SOCS-7 or cytokine-inducible SH2-containing protein-1 mRNAs. This suggests that ET-1 selectively affects particular types of SOCS family members. Changes in SOCS gene expressions induced by ET-1 may help explain the mechanism by which ET-1 modulates hormone signaling of adipocytes. [Copyright &y& Elsevier]

Abstract: An iron-based oxygen absorber (ABSO2RB®) activated by moisture was incorporated into a retort laminate and used to package chicken pesto with noodles. The effect of packaging material (regular MRE and oxygen-absorbing pouches) and reformulation with olive oil on the quality and shelf life of the entrée were investigated. Physical properties (color, texture, moisture, water activity), chemical properties (pH, TBARS), and microbiological quality (Total aerobic, coliforms, Escherichia coli, Yeast and Molds, Anaerobic plate counts) were measured in triplicates in an accelerated shelf-life study for 6 months at 37.8 °C. Samples stored at 26.7 °C for 12 months served as calibrated controls. Consumer and trained panel tests were carried out using a 9-point hedonic scale. The ABSO2RB® pouches performed well in terms of seal integrity and strength and limited the formation of rancid fatty acids in olive oil throughout the shelf-life study. Soybean formulations in ABSO2RB® pouches had the lowest (p < 0.05) Thiobarbituric Acid Reactive Substances (TBARS) value. Consumer and trained panelists accepted the olive oil formulations, in both packages. Results from this study will help MRE developers to expand the number of items using healthier oils. If future considerations to replace MRE packaging are needed, the ABSO2RB® film will be a suitable alternative. [Copyright &y& Elsevier]

Abstract: The effects of roasting, pressured-steam heating and microwave heating on total phenolics, total flavonoids, and antioxidant properties of whole-meal flour from tartary buckwheat (Fagopyrum tataricum Gaertn.) were investigated. The total phenolics were evaluated by Folin-Ciocalteau assay, total flavonoids by aluminum nitrate colorimetric assay whilst antioxidant properties were based on free radical scavenging activity of flour extracts against hydroxyl and superoxide anion radicals, and inhibition of lipid peroxidation in vitro. This study showed that thermal treatment of buckwheat flour caused a decrease in total phenolics, total flavonoids and antioxidative activities. The changes in trend of the antioxidant activities due to the thermal treatment were positively correlated with the content of phenolics (R 2 =0.8401–0.9909). Therefore, it can be suggested that special care should be taken when processing method is selected for the exploration of tartary buckwheat products. [Copyright &y& Elsevier]

Abstract: The effects of four single macromolecular crowding agents, Ficoll 70, dextran 70, polyethylene glycol (PEG) 2000, and calf thymus DNA (CT DNA), and three mixed crowding agents containing both CT DNA and polysaccharide (or PEG 2000) on the refolding of guanidine hydrochloride-denatured rabbit muscle creatine kinase (MM-CK) have been examined by activity assay. When the total concentration of the mixed crowding agent is 100 g/l, in which the weight ratio of CT DNA to Ficoll 70 is 1:9, the refolding yield of MM-CK after refolding for 3 h under these conditions increases 23% compared with that in the presence of 10 g/l CT DNA, 18% compared with 100 g/l Ficoll 70, and 19% compared with that in the absence of crowding agents. A remarkable increase in the refolding yield of MM-CK by a mixed crowding agent containing CT DNA and dextran 70 (or PEG 2000) is also observed. Further folding kinetics analyses show that these three mixed crowding agents remarkably accelerate the refolding of MM-CK, compared with single crowding agents. Aggregation of MM-CK in the presence of any of the three mixed crowding agents is less serious than that in the presence of a single crowding agent at the same concentration but more serious than that in the absence of crowding agents. Both the refolding yield and the refolding rate of MM-CK in mixtures of these agents are increased relative to the individual agents by themselves, indicating that mixed macromolecular crowding agents are more favorable to MM-CK folding and can be used to reflect the physiological environment more accurately than single crowding agents. [Copyright &y& Elsevier]

Abstract: The effects of oleic acid on amyloid formation of Ca2+-depleted bovine α-lactalbumin (apo-BLA) at low pH and the biological impact of the effects were investigated by using thioflavin T, Congo red, far-UV circular dichroism, atomic force microscopy, transmission electron microscopy, and other biophysical methods. The results from the phase diagram method of fluorescence show that two intermediates exist in the conformational transition of apo-BLA induced by low pH. One intermediate populated at pH 3.0 is characterized as a molten globule state and the other accumulates with stable secondary structure and exposed hydrophobic surface at pH 4.0–4.5. Amyloid formation of apo-BLA takes place upon decreasing the pH to 4.5 and is accelerated remarkably as the pH is decreased further. However, amyloid fibrils of apo-BLA are not observed in the pH range of 5.0–7.0 on a time-scale of 30 days. The lag time of fibrillation at pH 4.0 is greatly elongated by the presence of oleic acid, accompanied by a remarkable decline of the maximum thioflavin T intensity. Furthermore, amyloid formation of apo-BLA at pH 4.5 is inhibited completely by oleic acid, and insoluble aggregates are observed. In contrast, the effects of oleic acid on amyloid formation are not remarkable at pH 3.0 or at pH 2.0. Our data demonstrate that oleic acid specifically induces the intermediate of apo-BLA at pH 4.0–4.5 to form insoluble amorphous aggregates, which is responsible for the inhibition of amyloid formation of the protein by oleic acid in this range of pH values. [Copyright &y& Elsevier]

Abstract: Error analysis is very important to experimental designs. The error analysis of the determination of activity coefficients for a binary system via the isopiestic method shows that the error sources include not only the experimental errors of the analyzed molalities and the measured osmotic coefficients, but also the deviation of the regressed values from the experimental data when the regression function is used. It also shows that the accurate chemical analysis of the molality of the test solution is important, and it is preferable to keep the error of the measured osmotic coefficients changeless in all isopiestic experiments including those experiments on the very dilute solutions. The isopiestic experiments on the dilute solutions are very important, and the lowest molality should be low enough so that a theoretical method can be used below the lowest molality. And it is necessary that the isopiestic experiment should be done on the test solutions of lower than 0.1 mol·kg−1. For most electrolytes solutions, it is usually preferable to require the lowest molality to be less than 0.05 mol·kg−1. Moreover, the experimental molalities of the test solutions should be firstly arranged by keeping the interval of the logarithms of the molalities nearly constant, and secondly more number of high molalities should be arranged, and we propose to arrange the experimental molalities greater than 1 mol·kg−1 according to some kind of the arithmetical progression of the intervals of the molalities. After experiments, the error of the calculated activity coefficients of the solutes could be calculated from the actually values of the errors of the measured isopiestic molalities and the deviations of the regressed values from the experimental values with our obtained equations. [Copyright &y& Elsevier]

Streptococcus agalactiae is considered as a leading case of bacterial infection among neonates. Although relative protection strategies have been performed in many high-income countries, resulting in a massive reduction in the occurrences of early-onset GBS disease, the late-onset disease has not affected. Here, the whole genome of S. agalactiae Guangzhou-SAG036 was sequenced by the Pacific Biosciences Sequel using the P4–C2 chemistry and the continuous long reads were used for de novo assembly using HGAP. Besides, genes prediction and multiply annotation were performed by comparing it with diverse databases. The whole genome has a length of 2,206,504 bp and contains 2162 predicted genes with an average G + C content of 35.85%. Based on the whole genome sequence, 2 large prophages, 20 virulence factors genes, and 8 antibiotic resistant genes were identified. MLST analysis revealed S. agalactiae Guangzhou-SAG036 was identified as ST-17. The virulence factors genes were identified with different functions including adherence, antiphagocytosis, spreading factor, immune evasion, invasion, toxin. Besides, the antibiotic-resistant genes may provide S. agalactiae with resistance to multi-drugs including erythromycin, streptomycin, azithromycin, spiramycin, ampicillin, kanamycin, cationic peptides, and tetracycline. Therefore, the infection of S. agalactiae Guangzhou-SAG036 ST-17 strain maybe caused by the complex virulence factors and multi-drugs resistance. These results contribute to further understand GBS epidemiology and surveillance targets. • The whole genome of S. agalactiae Guangzhou-SAG036 has a length of 2,206,504 bp with an average G + C content of 35.85%. • The genome shows high similarity (99% identity) with two sequenced S. agalactiae strains isolated from China in 2016 and one isolated from Canada in 2010. • 2162 predicted genes had been identified containing two prophages. • MLST type was identified as ST-17. • 19 virulence factors genes and 8 antibiotic resistant genes were identified. [ABSTRACT FROM AUTHOR]

Lactobacillus brevis is a major contaminant of spoiled beer. And it was able to enter VBNC state and cause false negative detection, which poses a major challenge to the brewing industry. The genomic DNA of L. brevis BM-LB13908 was extracted and purified to form a sequencing library that meets the quality requirements and was sequenced. The sequencing results were then screened and assembled to obtain the entire genome sequence of L. brevis. Predicted genes were annotated by GO database, KEGG pathway database and COG functional classification system. The final assembly yielded 275 scaffolds of a total length of 2 840 080 bp with a G + C content of 53.35%. There were 2357, 701, 1519 predicted genes with corresponding GO functional, COG functional, and KEGG biological pathway annotations, respectively. The genome of L. brevis BM-LB13908 contains hop resistance gene horA and multiple genes related to the formation of VBNC state. This report describes the draft genome sequence of L. brevis BM-LB13908, a spoilage strain isolated from finished beer sample. This study may support further study on L. brevis and other beer spoilage bacteria, and prevent and control beer spoilage caused by microorganisms. • This report describes the draft genome sequence of L. brevis BM-LB13908, a spoilage strain isolated from finished beer sample. • The final assembly yielded 275 scaffolds of a total length of 2,840,080 bp with a G + C content of 53.35%. • 2357, 701 and 1519 predicted genes with corresponding GO functional, COG functional, and KEGG pathway annotations, respectively. • The genome of L. brevis BM-LB13908 contains hop resistance gene horA and multiple genes related to the VBNC state formation. [ABSTRACT FROM AUTHOR]

Methicillin-resistant S. aureus (MRSA) has been considered a potential "Super Bugs", responsible for various infectious diseases. Vancomycin has been the most effective antibitic to treat MRSA originated infections. In this study, we aimed at investigating the genomic features of a vancomycin intermediate-resistance S. aureus strain Guangzhou-SauVS2 isolated from a female patient suffering from chronic renal function failure, emphasizing on its antimicrobial resistance and virulence determinants. The genome has a total length of 2,605,384 bp and the G+C content of 33.21%, with 2,239 predicted genes annotated with GO terms, COG categories, and KEGG pathways. Besides the carriage of vancomycin b-type resistance protein responsible for the vancomycin intermediate-resistance, S. aureus strain Guangzhou-SauVS2 showed resistance to β-lactams, quinolones, macrolide, and tetracycline, due to the acquisition of corresponding antimicrobial resistance genes. In addition, virulence factors including adherence, antiphagocytosis, iron uptake, and toxin were determined, indicating the pathogenesis of the strain. • The carriage of vancomycin b-type resistance protein may contribute to the vancomycin intermediate-resistance. • β-lactam, quinolone, macrolide and tetracycline resistance may due to corresponding antibiotic resistance genes carriage. • The genome has a total length of 7,816,153 bp and the G+C content of 34.27%, with 6,697 predicted genes. • Virulence factors were determined, indicating the pathogenesis of the strain. [ABSTRACT FROM AUTHOR]

Gut microbiota and their metabolites (short-chain fatty acids, SCFAs) are associated with the pathogenesis of rheumatoid arthritis (RA). Total Clematis triterpenoid saponins (CTSs) prepared from Clematis mandshurica Rupr. possess therapeutic benefits for arthritic diseases. However, the poor pharmacokinetic properties of CTSs have obstructed the translation of these natural agents to drugs. Here, we examined the effects of CTSs on arthritis symptoms, gut microbiota and SCFAs in rats with collagen-induced arthritis (CIA). Our results showed that the arthritis index scores of CIA rats treated with CTSs were significantly lower than those of the model group. Most importantly, CTSs moderated gut microbial dysbiosis and significantly downregulated the total SCFA concentration in CIA rats. Compared to the control group, CTSs treatment have no significant side effects on the gut microbiota and SCFA metabolism in normal rats. Two differential analyses (LEfSe and DESeq2) were combined to study the details of the changes in gut microbiome, and twenty-four marker taxa at the genus level were identified via a comparison among control, model and CIA rats treated with high doses of CTSs. In particular, the mostly significantly increased gram-negative (G−) and decreased gram-positive (G+) genera in CIA rats were well restored by CTSs. The observed SCFA concentrations demonstrated that CTSs tend to maintain the balance of the gut microbiota. The data presented herein suggest that CTSs could ameliorate arthritis-associated gut microbial dysbiosis and may be potential adjuvant drugs that could provide relief from the gastrointestinal damage caused as a side effect of commonly used drugs. [ABSTRACT FROM AUTHOR]