A DNA tweezer-actuated nanozyme-enzyme hybrid nanoreactor for pesticide detection.

The construction of a nanozyme-enzyme hybrid cascade system is an effective protocol to optimize the performance of biosensors. Yet, the integration has limitations due to the lack of harmonious collaboration between nanozyme and enzyme. Herein, we have constructed an efficient enzymatic cascade system by utilizing the base complementary pairing and the targeting capability of DNA tweezers to combine DNA-regulated copper nanoflowers (CuNFs) with acetylcholinesterase (AChE).

Glutathione‑iron hybrid nanozyme-based colorimetric sensor for specific and stable detection of thiram pesticide on fruit juices.

Given the potential dangers of thiram to food safety, constructing a facile sensor is significantly critical. Herein, we presented a colorimetric sensor based on glutathione‑iron hybrid (GSH-Fe) nanozyme for specific and stable detection of thiram. The GSH-Fe nanozyme exhibits good peroxidase-mimicking activity with comparable Michaelis constant (K = 0.

The appointment-based model in community pharmacies: Patient demographics and reimbursable clinical services uptake in Ontario.

Background: Community pharmacies typically require patients to request medication refills. The appointment-based model (ABM) is a proactive approach that synchronizes refills and schedules patient-pharmacist appointments. These appointments provide opportunities for medication reviews, medication optimization and health promotion services.

Association of nutritional status and comorbidity with long-term survival among community-dwelling older males.

Background: Estimates of survival in the older can be of benefit in various facets, particularly in medical and individual decision-making. We aim to validate the value of a combination of nutrition status evaluation and comorbidity assessment in predicting long-term survival among community-dwelling older.

Methods: The Charlson Comorbidity Index (CCI) was applied for comprehensive evaluation of comorbidities.

Narciclasine, a novel topoisomerase I inhibitor, exhibited potent anti-cancer activity against cancer cells.

DNA topoisomerases are essential nuclear enzymes in correcting topological DNA errors and maintaining DNA integrity. Topoisomerase inhibitors are a significant class of cancer chemotherapeutics with a definite curative effect. Natural products are a rich source of lead compounds for drug discovery, including anti-tumor drugs.

LepR+ niche cell-derived AREG compromises hematopoietic stem cell maintenance under conditions of DNA repair deficiency and aging.

The cross talk between extrinsic niche-derived and intrinsic hematopoietic stem cell (HSC) factors controlling HSC maintenance remains elusive. Here, we demonstrated that amphiregulin (AREG) from bone marrow (BM) leptin receptor (LepR+) niche cells is an important factor that mediates the cross talk between the BM niche and HSCs in stem cell maintenance. Mice deficient of the DNA repair gene Brca2, specifically in LepR+ cells (LepR-Cre;Brca2fl/fl), exhibited increased frequencies of total and myeloid-biased HSCs.

Discovery of novel thymidylate synthase (TS) inhibitors that influence cancer angiogenesis and metabolic reprogramming in NSCLC cells.

Based on previous work, further search for more effective and less damaging thymidylate synthase (TS) inhibitors was the focus of this study. After further optimization of the structure, in this study, a series of (E)-N-(2-benzyl hydrazine-1-carbonyl) phenyl-2,4-deoxy-1,2,3,4-tetrahydro pyrimidine-5-sulfonamide derivatives were synthesized and reported for the first time. All target compounds were screened by enzyme activity assay and cell viability inhibition assay.

Implementation of the appointment-based model in community pharmacies: An analysis of refills and adherence.

Background: Traditionally, much of community pharmacy practice relies on patients to request their own medication refills. These refills are often not aligned, which has been shown to decrease adherence and workflow efficiencies. The appointment-based model (ABM) is designed to proactively synchronize refills and schedule patient-pharmacist appointments.

Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response.

Background: Envelope stress responses (ESRs) are critical for adaptive resistance of Gram-negative bacteria to envelope-targeting antimicrobial agents. However, ESRs are poorly defined in a large number of well-known plant and human pathogens. Dickeya oryzae can withstand a high level of self-produced envelope-targeting antimicrobial agents zeamines through a zeamine-stimulated RND efflux pump DesABC.

Investigation on Mechanical and Microstructure Properties of Silt Improved by Titanium Gypsum-Based Stabilizer.

Silt in the Yellow River alluvial plain is widely spread, but its uniform particle size and high roundness make it unsuitable as a subgrade filling material, while titanium gypsum (TG) is an industrial solid waste in Shandong Province, not only occupying land resources but also causing water and air pollution. In order to improve the engineering performance of silt, reduce the pollution of solid waste titanium gypsum to the environment and reduce the engineering cost, considering the engineering characteristics of titanium gypsum, it was combined in specific amounts with cement and lime to create a titanium gypsum-based stabilizer (TS) in this study. The effect of curing conditions and TS content on silt improvement was studied through laboratory experiments.

tRNA modification enzyme MiaB connects environmental cues to activation of Pseudomonas aeruginosa type III secretion system.

Pseudomonas aeruginosa, a major inhabitant of numerous environmental reservoirs, is a momentous opportunistic human pathogen associated with severe infections even death in the patients suffering from immune deficiencies or metabolic diseases. Type III secretion system (T3SS) employed by P. aeruginosa to inject effector proteins into host cells is one of the pivotal virulence factors pertaining to acute infections caused by this pathogen.

Markerless gene deletion in based on its natural transformation competence.

species complex (RSSC) is a group of Gram-negative bacterial pathogen capable of infecting numerous plants and crops, causing severe vascular wilt diseases. Functional analysis of the genes associated with bacterial virulence is critical for elucidating the molecular mechanisms that govern the bacterial pathogenicity. To this end, an efficient gene deletion method would be of great help.

Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis.

Platelets have emerged as key inflammatory cells implicated in the pathology of sepsis, but their contributions to rapid clinical deterioration and dysregulated inflammation have not been defined. Here, we show that the incidence of thrombocytopathy and inflammatory cytokine release was significantly increased in patients with severe sepsis. Platelet proteomic analysis revealed significant upregulation of gasdermin D (GSDMD).

A Bacterial Isolate Capable of Quenching Both Diffusible Signal Factor- and -Acylhomoserine Lactone-Family Quorum Sensing Signals Shows Much Enhanced Biocontrol Potencies.

-Acylhomoserine lactone (AHL) and diffusible signal factor (DSF) molecules are two families of widely conserved quorum sensing (QS) signals. Quorum quenching (QQ) via enzymatic inactivation of QS signals is a promising strategy of biocontrol. In the search for biocontrol agent quenching both AHL and DSF signals, it has been recently identified that DSF-quenching biocontrol agent sp.

Hematopoietic stem cell regeneration through paracrine regulation of the Wnt5a/Prox1 signaling axis.

The crosstalk between the BM microenvironment (niche) and hematopoietic stem cells (HSCs) is critical for HSC regeneration. Here, we show that in mice, deletion of the Fanconi anemia (FA) genes Fanca and Fancc dampened HSC regeneration through direct effects on HSCs and indirect effects on BM niche cells. FA HSCs showed persistent upregulation of the Wnt target Prox1 in response to total body irradiation (TBI).

Synthesis and evaluation of novel HER-2 inhibitors to exert anti-breast cancer ability through epithelial-mesenchymal transition (EMT) pathway.

Human epidermal growth factor receptor 2 (HER-2) is an essential member of the receptor tyrosine kinase (RTK) superfamily and has been reported as a critical method for treating HER-2 positive breast cancer. Here, we retained (E)-4-methyl-2-(4-(trifluoromethyl)styryl)oxazole, a fragment of HER-2 inhibitor Mubritinib, and synthesized 32 novel compounds from it. We screened out the most potential compound Q7j with HER-2 positive breast cancer cells through MTT assays, which possessed low toxicity on normal cells (MCF7-10A).

Spermidine Is an Intercellular Signal Modulating T3SS Expression in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a vital opportunistic human bacterial pathogen that causes acute and chronic infections. In this study, we set to determine whether the endogenous spermidine biosynthesis plays a role in regulation of type III secretion system (T3SS). The results showed that deletion of and , which encode putrescine biosynthesis, did not seem to affect cellular spermidine level and the T3SS gene expression.

Discovery of N-(1,3,4-thiadiazol-2-yl)benzamide derivatives containing a 6,7-methoxyquinoline structure as novel EGFR/HER-2 dual-target inhibitors against cancer growth and angiogenesis.

Targeting EGFR and HER-2 is an essential direction for cancer treatment. Here, a series of N-(1,3,4-thiadiazol-2-yl)benzamide derivatives containing a 6,7-methoxyquinoline structure was designed and synthesized to serve as EGFR/HER-2 dual-target inhibitors. The kinase assays verified that target compounds could inhibit the kinase activity of EGFR and HER-2 selectively.

Preventive effect of swim bladder hydrolysates on cyclophosphamide-induced ovarian injury in mice.

Aims: This study aimed to prepare swim bladder hydrolysate (SBH) with M  < 4000 Da, and investigate its effects on cyclophosphamide (CTX)-mediated ovarian injury in mice.

Methods: Hydrolysates were prepared by heating extraction, enzymatic hydrolysis and ultrafiltration. M and distribution of SBH were analyzed via gel filtration chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Quinacrine-CASIN combination overcomes chemoresistance in human acute lymphoid leukemia.

Chemoresistance posts a major hurdle for treatment of acute leukemia. There is increasing evidence that prolonged and intensive chemotherapy often fails to eradicate leukemic stem cells, which are protected by the bone marrow niche and can induce relapse. Thus, new therapeutic approaches to overcome chemoresistance are urgently needed.

The Two-Component System FleS/FleR Represses H1-T6SS via Cyclic di-GMP Signaling in Pseudomonas aeruginosa.

The type VI secretion system (T6SS) is an important translocation apparatus that is widely employed by Gram-negative bacteria to deliver toxic effectors into eukaryotic and prokaryotic target cells, causing host damage and providing competitive advantages in polymicrobial environments. The genome of Pseudomonas aeruginosa harbors three T6SS clusters (H1-T6SS, H2-T6SS, H3-T6SS). Activities of these systems are tightly regulated by a complicated signaling network which remains largely elusive.

Novel Allosteric Inhibitors of Deoxyhypusine Synthase against Malignant Melanoma: Design, Synthesis, and Biological Evaluation.

Based on the novel allosteric site of deoxyhypusine synthase (DHPS), two series of 30 novel 5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-amine derivatives as DHPS inhibitors were designed and synthesized. Among them, compound , with the best DHPS inhibitory potency (IC = 0.014 μM), exhibited excellent inhibition against melanoma cells, which was superior to that of GC7.

A newly identified polyunsaturated macamide alleviates dextran sulfate sodium-induced colitis in mice.

Macamides are a class of bioactive amide alkaloids found only in maca (Lepidium meyenii). Recent studies have shown that macamide-rich extracts possess various biological activities, such as antioxidative, immune-enhancing, and reproductive health-improving activities. In the present study, N-benzyl docosahexaenamide (NB-DHA), a newly identified macamide with the highest degree of unsaturation among all identified macamides, was identified from the maca extract.

FANCD2 and HES1 suppress inflammation-induced PPARɣ to prevent haematopoietic stem cell exhaustion.

The Fanconi anaemia protein FANCD2 suppresses PPAR to maintain haematopoietic stem cell's (HSC) function; however, the underlying mechanism is not known. Here we show that FANCD2 acts in concert with the Notch target HES1 to suppress inflammation-induced PPAR in HSC maintenance. Loss of HES1 exacerbates FANCD2-KO HSC defects.

Regulation of Exopolysaccharide Production by ProE, a Cyclic-Di-GMP Phosphodiesterase in PAO1.

The ubiquitous second messenger c-di-GMP is involved in regulation of multiple biological functions including the important extracellular matrix exopolysaccharides (EPS). But how c-di-GMP metabolic proteins influence EPS and their enzymatic properties are not fully understood. Here we showed that deletion of , which encodes a protein with GGDEF-EAL hybrid domains, significantly increased the transcriptional expression of the genes encoding EPS production in PAO1 and changed the bacterial colony morphology.