Notes

World-wide transcriptome and mutagenic examines with the acidity building up a tolerance reply of Salmonella enterica serovar Typhimurium.
In combination with antibacterial properties, the adhesion and proliferation profiles of the GAG derivatives enabled the selection of the most promising wound healing candidates for subsequent in vivo studies. A P. aeruginosa-infected murine wound model revealed the benefits of CS over HA as a pro-wound healing NO donor scaffold, with benefits of accelerated wound closure and decreased bacterial burden attributable to both active NO release and the biopolymer backbone.The pKBHX (logarithm of complexation constant K of 4-fluorophenol with bases) hydrogen-bond basicity scale of neutral hydrogen-bond acceptors (HBAs) is extended to anionic HBAs. The scale is constructed for 26 anions through (i) the infrared measurement of K on NBu4+X- ion pairs in CCl4, (ii) the estimation of K from linear free energy relationships between measured K values and literature K values for various phenols in polar solvents, and (iii) the computation of K at the density functional theory level in CCl4. The scale extends on a 9.4 pK unit range from fluoride to tetraphenylborate. Considering a number of anions as organic functions substituted with unipolar substituents, their pKBHX values can be related to the Hammett-Taft substituent constants σ. Unipolar substituents (O- and S-) obey the same pKBHX versus σ relationships as dipolar ionic (N-N+R3) and dipolar (OH, CF3, NR2, or OR) ones for the nitrile, carbonyl, nitroso, nitro, sulfonyl, and phosphoryl functions. Like dipolar substituents, unipolar substituents at carbon and nitrogen operate by field-inductive and resonance effects, whereas substituents at sulfur and phosphorus operate only by the field-inductive effect.
Virtual cutting of deformable objects plays an important role in many applications, especially in digital medicine, such as soft tissue cutting in virtual surgery training system.

We developed a novel virtual cutting algorithm, combined with mesh optimisation. A new local mesh processing method is used to control the number and quality of the elements created during the cutting process. At the same time, high-order tetrahedral elements are used to fit the cutting surface and reduce the mesh size.

In this paper, single cut, multiple cut and intersecting cut are performed on the mesh model, combined with a force feedback device, and the result obtained is that the visual feedback is higher than 30Hz, and the tactile feedback is 800∼1000Hz.

Experimental results show that the method proposed in this paper can effectively eliminate low-quality elements and control the mesh size, thereby ensuring real-time simulation.
Experimental results show that the method proposed in this paper can effectively eliminate low-quality elements and control the mesh size, thereby ensuring real-time simulation.Phycocyanobilin (PCB) is a kind of light-harvesting pigment which naturally exists in algae and plays important roles in absorbing and transferring energy. Based on its antioxidant and optical properties, PCB has been applied in food, medicine, and cosmetics. Currently, PCB is mainly extracted from Spirulina through complicated steps; thus, the biosynthesis of PCB in Escherichia coli has attracted more attention. However, due to the lower catalytic efficiency of synthetic enzymes and the deficiency of precursors and cofactors, the titer of PCB remains at a low level. Here, we report the efficient synthesis of PCB by the expression of heme oxygenase-1 from Thermosynechococcus elongatus and PCB ferredoxin oxidoreductase (PcyA) from Synechocystis sp. using a high-copy number plasmid with an inducible T7lac promoter and the assembly of these two enzymes at a suitable ratio of 21 with DNA scaffolds. Additionally, the synthesis of PCB was further enhanced by direct supplementation of 5-aminolevulinic acid (ALA), moderate overexpression of key enzymes in the heme biosynthetic pathway (hemB and hemH), and accelerated cycle of cofactors (NADPH) through the expression of NAD+ kinase and the addition of a reducing agent. Finally, based on the optimal conditions (Modified R medium with 200 mg/L ALA, 20 mg/L FeSO4·7H2O, and 5 g/L vitamin C induced by 0.8 mM isopropylthio-β-galactoside at 30 °C), the highest reported titer of PCB (28.32 mg/L) was obtained at the fermenter level by feeding glucose and FeSO4·7H2O. The strategies applied in this study will be useful for the synthesis of other natural pigments and PCB or heme derivatives in E. coli.Fine-tuning the alkyl chains and end groups of non-fused ring electron acceptors (NFREAs) plays vital roles in the promotion of charge transfer (CT) and power conversion efficiency (PCE). In this work, we developed a series of A-D-A'-D-A-type NFREAs, which possess the same terminals (A), the cyclopentadithiophene unit (D), and the thieno[3,4-c]pyrrole-4,6-dione (A'). Despite the subtle difference in side chains and halogenated end groups, the six acceptors exhibit a considerable difference in the efficiency and device stability of the organic solar cells (OSCs). Among the molecules, chlorinated NFREAs show a broader light absorption than the fluorinated ones do. Compared with C8C8-4F (1-octylnonyl and fluorination) and C6C4-4Cl (2-butyloctyl and chlorination), C8C8-4Cl (1-octylnonyl and chlorination) exhibits a lower highest occupied molecular orbital level, higher electron mobility, and denser molecular packing. The OSCs based on PM6C8C8-4Cl yield the best PCE of 14.11%, which is attributed to the faster charge transport, high miscibility, and preferable morphology. Moreover, the PM6C8C8-4Cl devices retain 91.1% of the initial PCE after being placed in air with 67% relative humidity for 50 days. This work shows that the simultaneous optimization of side chains and end groups facilitates the CT and improves the stability in the OSCs, offering a novel view into the molecular design of A-D-A'-D-A-type NFREAs.Hemophilic arthropathy (HA) is characterized by joint damage following recurrent joint bleeds frequently observed in patients affected by the clotting disorder hemophilia. Vevorisertib Joint bleeds or hemarthroses trigger inflammation in the synovial tissue, which promotes damage to the articular cartilage. The plasminogen activation system is integral to fibrinolysis, and the urokinase plasminogen activator, or uPA in particular, is strongly upregulated following hemarthroses. uPA is a serine protease that catalyzes the production of plasmin, a broad-spectrum protease that can degrade fibrin as well as proteins of the joint extracellular matrix and cartilage. Both uPA and plasmin are able to proteolytically generate active forms of matrix metalloproteinases (MMPs). The MMPs are a family of >20 proteases that are secreted as inactive proenzymes and are activated extracellularly. MMPs are involved in the degradation of all types of collagen and proteoglycans that constitute the extracellular matrix, which provides structural support to articular cartilage. The MMPs have an established role in joint destruction following rheumatoid arthritis (RA). They degrade cartilage and bone, indirectly promoting angiogenesis. MMPs are also implicated in the pathology of osteoarthritis (OA), characterized by degradation of the cartilage matrix that precipitates joint damage and deformity. HA shares a number of overlapping pathological characteristics with RA and OA. Here we discuss how the plasminogen activation system and MMPs might exacerbate joint damage in HA, lending insight into novel possible therapeutic targets to reduce the comorbidity of hemophilia.The stimulation of sarcoplasmic reticulum calcium ATPase SERCA2a emerged as a novel therapeutic strategy to efficiently improve overall cardiac function in heart failure (HF) with reduced arrhythmogenic risk. Istaroxime is a clinical-phase IIb compound with a double mechanism of action, Na+/K+ ATPase inhibition and SERCA2a stimulation. Starting from the observation that istaroxime metabolite PST3093 does not inhibit Na+/K+ ATPase while stimulates SERCA2a, we synthesized a series of bioisosteric PST3093 analogues devoid of Na+/K+ ATPase inhibitory activity. Most of them retained SERCA2a stimulatory action with nanomolar potency in cardiac preparations from healthy guinea pigs and streptozotocin (STZ)-treated rats. One compound was further characterized in isolated cardiomyocytes, confirming SERCA2a stimulation and in vivo showing a safety profile and improvement of cardiac performance following acute infusion in STZ rats. We identified a new class of selective SERCA2a activators as first-in-class drug candidates for HF treatment.Acquired T-cell dysfunction is characteristic of chronic lymphocytic leukemia (CLL) and is associated with reduced efficacy of T cell-based therapies. A recently described feature of dysfunctional CLL-derived CD8 T cells is reduced metabolic plasticity. To what extend CD4 T cells are affected and whether CD4 T-cell metabolism and function can be restored upon clinical depletion of CLL cells are currently unknown. We address these unresolved issues by comprehensive phenotypic, metabolic, transcriptomic, and functional analysis of CD4 T cells of untreated patients with CLL and by analysis of the effects of venetoclax plus obinutuzumab on the CD4 population. Resting CD4 T cells derived from patients with CLL expressed lower levels of GLUT-1 and displayed deteriorated oxidative phosphorylation (OXPHOS) and overall reduced mitochondrial fitness. Upon T-cell stimulation, CLL T cells were unable to initiate glycolysis. Transcriptome analysis revealed that depletion of CLL cells in vitro resulted in upregulation of OXPHOS and glycolysis pathways and restored T-cell function in vitro. Analysis of CD4 T cells from patients with CLL before and after venetoclax plus obinutuzumab treatment, which led to effective clearance of CLL in blood and bone marrow, revealed recovery of T-cell activation and restoration of the switch to glycolysis, as well as improved T-cell proliferation. Collectively, these data demonstrate that CLL cells impose metabolic restrictions on CD4 T cells, which leads to reduced CD4 T-cell functionality. This trial was registered in the Netherlands Trial Registry as #NTR6043.Enabling a biodegradable polymer radiopaque under X-ray is much desired for many medical devices. Physical blending of a present biodegradable polymer and a commercialized medical contrast agent is convenient yet lacks comprehensive fundamental research. Herein, we prepared a biodegradable polymer-based radiopaque raw material by blending poly(l-lactic acid) (PLLA or simply PLA) and iohexol (IHX), where PLA constituted the continuous phase and IHX particles served as the dispersed phase. The strong X-ray adsorption of IHX enabled the composite radiopaque; the hydrolysis of the polyester and the water solubility of the contrast agent enabled the composite biodegradable in an aqueous medium. The idea was confirmed by in vitro characterizations of the resultant composite, in vivo subcutaneous implantation in rats up to 6 months, and the clear visualization of a part of a biodegradable occluder in a Bama piglet under X-ray. We also found that the crystallization of PLA was significantly enhanced in the presence of the solid particles, which should be taken into consideration in the design of an appropriate biomaterial composite because crystallization degree influences the biodegradation rate and mechanical property of a material to a large extent. We further tried to introduce a small amount of poly(vinylpyrrolidone) into the blend of PLA and IHX. Compared to the bicomponent composite, the tricomponent one exhibited decreased modulus and increased elongation at break and tensile strength. This paves more ways for researchers to select appropriate raw materials according to the regenerated tissue and the application site.
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