Brain and cancer associated binding domain mutations provide insight into CTCF's relationship with chromatin and its ability to act as a chromatin organizer.

Although only a fraction of CTCF motifs are bound in any cell type, and approximately half of the occupied sites overlap cohesin, the mechanisms underlying cell-type specific attachment and ability to function as a chromatin organizer remain unknown. To investigate the relationship between CTCF and chromatin we applied a combination of imaging, structural and molecular approaches, using a series of brain and cancer associated CTCF mutations that act as CTCF perturbations. We demonstrate that binding and the functional impact of WT and mutant CTCF depend not only on the unique properties of each protein, but also on the genomic context of bound sites.

MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data.

Aberrations in the capacity of DNA/chromatin modifiers and transcription factors to bind non-coding regions can lead to changes in gene regulation and impact disease phenotypes. However, identifying distal regulatory elements and connecting them with their target genes remains challenging. Here, we present MethNet, a pipeline that integrates large-scale DNA methylation and gene expression data across multiple cancers, to uncover cis regulatory elements (CREs) in a 1 Mb region around every promoter in the genome.

Brain and cancer associated binding domain mutations provide insight into CTCF's relationship with chromatin and its contribution to gene regulation.

Here we used a series of CTCF mutations to explore CTCF's relationship with chromatin and its contribution to gene regulation. CTCF's impact depends on the genomic context of bound sites and the unique binding properties of WT and mutant CTCF proteins. Specifically, CTCF's signal strength is linked to changes in accessibility, and the ability to block cohesin is linked to its binding stability.

Ciprofloxacin-Loaded, pH-Responsive PAMAM-Megamers Functionalized with S-Nitrosylated Hyaluronic Acid Support Infected Wound Healing in Mice without Inducing Antibiotic Resistance.

Antimicrobial-resistant bacterial infections threaten to become the number one cause of death by the year 2050. Since the speed at which antimicrobial-resistance develops is exceeding the pace at which new antimicrobials come to the market, this threat cannot be countered by making more, new and stronger antimicrobials. Promising new antimicrobials should not only kill antimicrobial-resistant bacteria, but also prevent development of new bacterial resistance mechanisms in strains still susceptible.

MethNet: a robust approach to identify regulatory hubs and their distal targets in cancer.

Aberrations in the capacity of DNA/chromatin modifiers and transcription factors to bind non-coding regions can lead to changes in gene regulation and impact disease phenotypes. However, identifying distal regulatory elements and connecting them with their target genes remains challenging. Here, we present MethNet, a pipeline that integrates large-scale DNA methylation and gene expression data across multiple cancers, to uncover novel cis regulatory elements (CREs) in a 1Mb region around every promoter in the genome.

A Heterocatalytic Metal-Organic Framework to Stimulate Dispersal and Macrophage Combat with Infectious Biofilms.

Eradication of infectious biofilms is becoming increasingly difficult due to the growing number of antibiotic-resistant strains. This necessitates development of nonantibiotic-based, antimicrobial approaches. To this end, we designed a heterocatalytic metal-organic framework composed of zirconium 1,4-dicarboxybenzene (UiO-66) with immobilized Pt nanoparticles (Pt-NP/UiO-66).

Influence of interaction between surface-modified magnetic nanoparticles with infectious biofilm components in artificial channel digging and biofilm eradication by antibiotics and .

Magnetic targeting of antimicrobial-loaded magnetic nanoparticles to micrometer-sized infectious biofilms is challenging. Bacterial biofilms possess water channels that facilitate transport of nutrient and metabolic waste products, but are insufficient to allow deep penetration of antimicrobials and bacterial killing. Artificial channel digging in infectious biofilms involves magnetically propelling nanoparticles through a biofilm to dig additional channels to enhance antimicrobial penetration.

PAMAM dendrimers with dual-conjugated vancomycin and Ag-nanoparticles do not induce bacterial resistance and kill vancomycin-resistant Staphylococci.

The effective life-time of new antimicrobials until the appearance of the first resistant strains is steadily decreasing, which discourages incentives for commercialization required for clinical translation and application. Therefore, development of new antimicrobials should not only focus on better and better killing of antimicrobial-resistant strains, but as a paradigm shift on developing antimicrobials that prevent induction of resistance. Heterofunctionalized, poly-(amido-amine) (PAMAM) dendrimers with amide-conjugated vancomycin (Van) and incorporated Ag nanoparticles (AgNP) showed a 6-7 log reduction in colony-forming-units of a vancomycin-resistant Staphylococcus aureus strain in vitro, while not inducing resistance in a vancomycin-susceptible strain.

Effect of acupoint therapy combined with spine pinching in patients with menopausal syndrome: a randomized controlled trial.

Objective: To assess the efficacy of acupoint therapy combined with spine pinching in patients with menopausal syndrome.

Methods: This is a parallel, randomized, controlled, investigator-blinded trial. A total of 132 participants were randomly assigned to receive either acupoint therapy combined with spine pinching (intervention group) or tibolone therapy alone (control group).

Circumventing antimicrobial-resistance and preventing its development in novel, bacterial infection-control strategies.

Introduction: Development of new antimicrobials with ever 'better' bacterial killing has long been considered the appropriate response to the growing threat of antimicrobial-resistant infections. However, the time-period between the introduction of a new antibiotic and the appearance of resistance amongst bacterial pathogens is getting shorter and shorter. This suggests that alternative pathways than making ever 'better' antimicrobials should be taken.

Folic acid-modified fluorescent dye-protein nanoparticles for the targeted tumor cell imaging.

Serum albumin has a wide range of applications in biochemical experiments and pharmaceutical field. We found that a cyanine dye, dimethylindole red (Dir), could selectively interact with bovine serum albumin (BSA). Dir exhibited very weak red fluorescence, while the fluorescence intensity at 630 nm was enhanced up to 130-fold upon noncovalently interacting with 30 µM BSA.

The Mevalonate Pathway Is a Druggable Target for Vaccine Adjuvant Discovery.

Motivated by the clinical observation that interruption of the mevalonate pathway stimulates immune responses, we hypothesized that this pathway may function as a druggable target for vaccine adjuvant discovery. We found that lipophilic statin drugs and rationally designed bisphosphonates that target three distinct enzymes in the mevalonate pathway have potent adjuvant activities in mice and cynomolgus monkeys. These inhibitors function independently of conventional "danger sensing.

Decidual Stromal Cell Necroptosis Contributes to Polyinosinic-Polycytidylic Acid-Triggered Abnormal Murine Pregnancy.

Infectious agents can reach the placenta either the maternal blood or by ascending the genito-urinary tract, and then initially colonizing the maternal decidua. Decidual stromal cells (DSCs) are the major cellular component of the decidua. Although DSCs at the maternal-fetal interface contribute to the regulation of immunity in pregnancy in the face of immunological and physiological challenges, the roles of these DSCs during viral infection remain ill defined.

Effects of electroacupuncture on the cortical extracellular signal regulated kinase pathway in rats with cerebral ischaemia/reperfusion.

Objective: To explore the effects of electroacupuncture (EA) on the phosphorylated extracellular signal regulated kinase (p-ERK) pathway of the cerebral cortex in a rat model of focal cerebral ischaemia/reperfusion (I/R).

Methods: 160 adult Sprague-Dawley rats underwent middle carotid artery occlusion (MCAO) to establish I/R injury and were randomly divided into four groups (n=40 each) that remained untreated (I/R group) or received EA at LU5, LI4, ST36 and SP6 (I/R+EA group), the ERK inhibitor PD98059 (I/R+PD group), or both interventions (I/R+PD+EA groups). An additional 40 rats undergoing sham surgery formed a healthy control group.

Effect of bloodletting therapy at local myofascial trigger points and acupuncture at Jiaji (EX-B 2) points on upper back myofascial pain syndrome: a randomized controlled trial.

Objective: To observe the clinical efficacy of bloodletting therapy and acupuncture at Jiaji points for treating upper back myofascial pain syndrome (MPS), and compare this with lidocaine block therapy.

Methods: A total of 66 upper back MPS patients were randomly assigned to either the treatment group or the control group in a 1: 1 ratio. The treatment group (n = 33) were treated with bloodletting therapy at local myofascial trigger points and acupuncture at Jiaji (EX-B 2) points; one treatment course consisted of five, single 20-min-treatments with a 2-day break between each treatment.

DNA sequence-dependent fluorescence of doxorubicin for turn-on detection of biothiols in human serum.

Doxorubicin (Dox) is a DNA-targeting anthracycline antibiotic active against a wide spectrum of cancers. The interaction between Dox and double-stranded DNA (dsDNA) was used to load Dox using DNA duplexes as carriers. More importantly, the interesting DNA sequence-dependent fluorescence response of Dox could be exploited in the design of efficient Dox release systems and efficient fluorescence sensors.

Responses of rose RhACS1 and RhACS2 promoters to abiotic stresses in transgenic Arabidopsis thaliana.

Promoter activities of RhACS1 and RhACS2 , two rose genes involved in ethylene biosynthesis, are highly sensitive to various abiotic stresses in an organ-specific manner. Our previous studies indicated that two rose (Rosa hybrida) 1-aminocyclopropane-1-carboxylic acid synthase genes, RhACS1 and RhACS2, play a role in dehydration-induced ethylene production and inhibition of cell expansion in rose petals. Here, both RhACS1 and RhACS2 promoters were analyzed using histochemical staining and glucuronidase synthase (GUS) gene reporter activity assays following their introduction into transgenic Arabidopsis thaliana plants.

The rose (Rosa hybrida) NAC transcription factor 3 gene, RhNAC3, involved in ABA signaling pathway both in rose and Arabidopsis.

Plant transcription factors involved in stress responses are generally classified by their involvement in either the abscisic acid (ABA)-dependent or the ABA-independent regulatory pathways. A stress-associated NAC gene from rose (Rosa hybrida), RhNAC3, was previously found to increase dehydration tolerance in both rose and Arabidopsis. However, the regulatory mechanism involved in RhNAC3 action is still not fully understood.

Cytosolic double-stranded DNA induces nonnecroptotic programmed cell death in trophoblasts via IFI16.

The mechanisms underlying the immune defense by trophoblasts against pathogens remain ill defined. We demonstrated that placental cell death was increased upon in vivo exposure to Listeria monocytogenes. The death of infected cells is an important host innate defense mechanism.

RhHB1 mediates the antagonism of gibberellins to ABA and ethylene during rose (Rosa hybrida) petal senescence.

Rose (Rosa hybrida) is one of the most important ornamental plants worldwide; however, senescence of its petals terminates the ornamental value of the flower, resulting in major economic loss. It is known that the hormones abscisic acid (ABA) and ethylene promote petal senescence, while gibberellins (GAs) delay the process. However, the molecular mechanisms underlying the antagonistic effects amongst plant hormones during petal senescence are still unclear.

RhNAC3, a stress-associated NAC transcription factor, has a role in dehydration tolerance through regulating osmotic stress-related genes in rose petals.

Petal cell expansion depends on cell wall metabolism, changes in cell turgor pressure and restructuring of the cytoskeleton, and recovery ability of petal cell expansion is defined as an indicator of dehydration tolerance in flowers. We previously reported that RhNAC2, a development-related NAC domain transcription factor, confers dehydration tolerance through regulating cell wall-related genes in rose petals. Here, we identify RhNAC3, a novel rose SNAC gene, and its expression in petals induced by dehydration, wounding, exogenous ethylene and abscisic acid (ABA).

[Comparative study on effect of acupuncture and lidocaine block for lumbar myofascial pain syndrome].

Objective: To observe the clinical efficacy of acupuncture at Jiaji (EX-B 2) points mainly for lumbar myofascial pain syndrome (MPS).

Methods: Sixty-six cases of MPS were randomized into an acupuncture group and a lidocaine group, 33 cases in each group. The acupuncture group was treated with acupuncture at Jiaji (EX-B 2) points combined with needling local myofascial trigger points (MTrP), and the lidocaine group was treated with local block at trigger points with lidocaine injection.