Hastingshenson3052

Hard coatings are primarily based on carbides, nitrides and carbonitrides of transition metal elements such as W, Ti, Zr, etc. Zr-based hard coatings show good resistance to wear, erosion, and corrosion as well as exhibit high hardness, high temperature stability, and biocompatibility, making them suitable candidates for tribological, biomedical, and electrical applications.

The present study aims to synthesize uniform and adherent hard Zr-based coatings that demonstrate sound mechanical integrity.

Stainless steel (SS316) samples were coated with single layers of Zr, Zr-nitride, and Zr-carbonitride using magnetron sputter deposition technique. Deposition conditions were controlled to produce each coating with two different thickness i.e., 2 and 3μm. Calotest was employed to confirm coatings thickness. Scanning electron microscope fitted with energy dispersive x-ray spectrometer was used to ascertain the morphology and elemental constitution of coatings. Cross-sectional samples were examined to ascertain coatings thickness and adhesion. X-ray diffractometer was employed for structural analysis. Instrumented nanoindentation hardness and elastic modulus were determined with nanoindenter. Ratio of nanohardness to elastic modulus was evaluated to observe the effect of coatings thickness on tribological behavior.

Three coating compositions were produced namely hcp-Zr, fcc-ZrN and fcc-Zr

CN. The highest hardness and elastic modulus were shown by ZrN coatings while pure Zr coatings showed the lowest values.

All coating compositions were found to be relatively uniform, continuous and adherent with no evidence of decohesion at the coating-substrate interface. Coatings produced in this study are thought to be suitable for tribological applications.

All coating compositions were found to be relatively uniform, continuous and adherent with no evidence of decohesion at the coating-substrate interface. Coatings produced in this study are thought to be suitable for tribological applications.

The inhibitory glycine receptor (GlyR), a mediator of fast synaptic inhibition, is located and held at neuronal synapses through the anchoring proteins gephyrin and collybistin. Stable localization of neurotransmitter receptors is essential for synaptic function. In case of GlyRs, only beta subunits were known until now to mediate synaptic anchoring.

We identified a poly-proline II helix (PPII) in position 365-373 of the intra-cellular TM3-4 loop of the human GlyRα1 subunit as a novel potential synaptic anchoring site. The potential role of the PPII helix as synaptic anchoring site was tested.

Glycine receptors and collybistin variants were generated and recombinantly expressed in HEK293 cells and cultured neurons. Receptor function was assessed using patch-clamp electrophysiology, protein-protein interaction was studied using co-immuno-precipitation and pulldown experiments.

Recombinantly expressed collybistin bound to isolated GlyRα1 TM3-4 loops in GST-pulldown assays. When the five proline residuesro and in vivo and may contribute to postsynaptic anchoring of glycine receptors.

Inflammation is a key factor in myocardial ischemia/reperfusion (MI/R) injury. Targeting leucocyte-mediated inflammation is an important strategy for MI/R therapy. Iminostilbene (ISB), a simple dibenzoazepine small molecule compound, has a strong anti-neurodegenerative effect. However, no study has shown the cardioprotective effect of ISB.

This study aimed to investigate the role of ISB against MI/R injury and identify its molecular target.

To verify the cardiac protection of ISB

and

, we performed rat MI/R surgery and subjected inflammatory modeling of macrophages. In terms of molecular mechanisms, we designed and synthesized a small molecular probe of ISB and employed it on the click chemistry-activity-based protein profiling technique to fish for ISB targets in macrophages. To identify the target, we applied the competitive inhibition assay, surface-plasmon resonance (SPR), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay.

, ISB showed robust anti-myocardial injury activity by improving cardiac function, reducing myocardial infarction, and inhibiting macrophage-mediated inflammation. TGF-beta signaling

, ISB strongly inhibited the transcription and the expression levels of inflammatory cytokines in macrophages. The pyruvate kinase isozyme type M2 (PKM2) was identified as the potential target of ISB through proteomic analysis and the competitive assay was performed for specific binding verification. Further thermodynamic and kinetic experiments showed that ISB was bound to PKM2 in a dose-dependent manner. Moreover, in terms of the biological function of ISB on PKM2, ISB reduced the expression of PKM2, thereby reducing the expression of HIF1α and the phosphorylation of STAT3.

This study for the first time demonstrated that ISB targeted PKM2 to reduce macrophage inflammation thereby significantly alleviating MI/R injury.

This study for the first time demonstrated that ISB targeted PKM2 to reduce macrophage inflammation thereby significantly alleviating MI/R injury.

The tear proteomics and neuromediators are associated with clinical dry eye parameters following refractive surgery.

To investigate and compare the tear proteomic and neuromediator profiles following small incision lenticule extraction (SMILE) versus laser-assisted in-situ keratomileusis (LASIK).

In this randomized controlled trial with paired-eye design, 70 patients were randomized to receive SMILE in one eye and LASIK in the other eye. Tear samples were collected preoperatively, and 1 week, 1, 3, 6 and 12 months postoperatively, and were examined for protein concentration changes using sequential window acquisition of all theoretical fragment ion mass spectrometry (SWATH-MS). The data were analyzed with DAVID Bioinformatics Resources for enriched gene ontology terms and over-represented pathways. Tear neuromediators levels were correlated with clinical parameters.

Post-SMILE eyes had significantly better Oxford staining scores and tear break-up time (TBUT) than post-LASIK eyes at 1 and 3 months, respectively. Tear substance P and nerve growth factor levels were significantly higher in the LASIK group for 3 months and 1 year, respectively. SMILE and LASIK shared some similar biological responses postoperatively, but there was significant up-regulation in leukocyte migration and wound healing at 1 week, humoral immune response and apoptosis at 1 month, negative regulation of endopeptidase activity at 3 to 6 months, and extracellular structure organization at 1 year in the post-LASIK eyes. Tear mucin-like protein 1 and substance P levels were significantly correlated with TBUT (

=-0.47,

=-0.49, respectively).

Significant differences in the tear neuromediators and proteomics were observed between SMILE and LASIK, even though clinical dry eye signs have subsided and became comparable between 2 procedures.

Significant differences in the tear neuromediators and proteomics were observed between SMILE and LASIK, even though clinical dry eye signs have subsided and became comparable between 2 procedures.

Mast cell (MC) degranulation is an important step in the pathogenesis of inflammatory reactions and allergies; however, the mechanism of stabilizing MC membranes to reduce their degranulation is unclear.

SO

content in MC culture supernatant was measured by HPLC-FD. The protein and mRNA expressions of the key enzymes aspartate aminotransferase 1 (AAT1) and AAT2 and intracellular AAT activity were detected. The cAMP level in MCs was detected by immunofluorescence and ELISA. The release rate of MC degranulation marker β-hexosaminidase was measured. The expression of AAT1 and cAMP, the MC accumulation and degranulation in lung tissues were detected.

To exam whether an endogenous sulfur dioxide (SO

) pathway exists in MCs and if it serves as a novel endogenous MC stabilizer.

We firstly show the existence of the endogenous SO

/AAT pathway in MCs. Moreover, when AAT1 was knocked down in MCs, MC degranulation was significantly increased, and could be rescued by a SO

donor. Mechanistically, AAT1 knockdowO2 serves as an endogenous MC stabilizer via upregulating the cAMP pathway under hypoxic circumstance.

The US Food and Drug Administration (FDA) has approved several immunotherapeutic drugs for cancer since 2010, and many more are still being evaluated in other clinical studies. These inhibitors significantly increase response rates and result in the treatment of patients with advanced cancer. However, cancer immunotherapy leads to essential cardiac toxicity properties that have become distinct from other cancer patients' care and are mostly related to their etiology.

As potential implications, the occurrence of cardiovascular adverse events is particularly challenging and needs a comprehensive understanding of overall cancer-related etiology, clinical outcomes with different variable severity, and management.

In terms of improving the overall survival of patients with cancer, clinicians should be careful in selecting either programmed cell death-1 (PD-1) or its programmed cell death ligand (PDL-1) inhibitors by evaluating their risk and clinical benefit for early intervention and decrease the level of morbidity and mortality of their patients. This review focuses on the effectiveness of PD-1/PL-1 antibodies and associated cardiotoxicity adverse events, including etiological mechanisms, diagnosis, and treatment.

In terms of improving the overall survival of patients with cancer, clinicians should be careful in selecting either programmed cell death-1 (PD-1) or its programmed cell death ligand (PDL-1) inhibitors by evaluating their risk and clinical benefit for early intervention and decrease the level of morbidity and mortality of their patients. This review focuses on the effectiveness of PD-1/PL-1 antibodies and associated cardiotoxicity adverse events, including etiological mechanisms, diagnosis, and treatment.

Previous studies reported the beneficial effects of pretreatment with melatonin on the heart during cardiac ischemia/reperfusion (I/R) injury. However, the effects of melatonin given after cardiac ischemia, as well as its comparative temporal effects are unknown. These include pretreatment, during ischemia, and at the onset of reperfusion. Also, the association between melatonin receptors and cardiac arrhythmias, mitochondrial function and dynamics, autophagy, and mitophagy during cardiac I/R have not been investigated.

We tested two major hypotheses in this study. Firstly, the temporal effect of melatonin administration exerts different cardioprotective efficacy during cardiac I/R. Secondly, melatonin provides cardioprotective effects via MT2 activation, leading to improvement in cardiac mitochondrial function and dynamics, reduced excessive mitophagy and autophagy, and decreased cardiac arrhythmias, resulting in improved LV function.

Male rats were subjected to cardiac I/R, and divided into 4 intervenre or after ischemia exerted equal levels of cardioprotection on the heart with I/R injury, and its beneficial effects on cardiac arrhythmias, cardiac mitochondrial function and dynamics were dependent upon the activation of MT2.