Role of Mod(mdg4)-67.2 Protein in Interactions between Su(Hw)-Dependent Complexes and Their Recruitment to Chromatin.

Su(Hw) belongs to the class of proteins that organize chromosome architecture, determine promoter activity, and participate in formation of the boundaries/insulators between the regulatory domains. This protein contains a cluster of 12 zinc fingers of the C2H2 type, some of which are responsible for binding to the consensus site. The Su(Hw) protein forms complex with the Mod(mdg4)-67.2 and the CP190 proteins, where the last one binds to all known Drosophila insulators. To further study functioning of the Su(Hw)-dependent complexes, we used the previously described su(Hw)E8 mutation with inactive seventh zinc finger, which produces mutant protein that cannot bind to the consensus site. The present work shows that the Su(Hw)E8 protein continues to directly interact with the CP190 and Mod(mdg4)-67.2 proteins. Through interaction with Mod(mdg4)-67.2, the Su(Hw)E8 protein can be recruited into the Su(Hw)-dependent complexes formed on chromatin and enhance their insulator activity. Our results demonstrate that the Su(Hw) dependent complexes without bound DNA can be recruited to the Su(Hw) binding sites through the specific protein-protein interactions that are stabilized by Mod(mdg4)-67.2.

Topological tight binding models on some non-trivial lattices: Union of geometry, flat bands and topology.

We introduce a topological tight binding model based on certain rules that we have formulated to study systems with certain non-trivial bulks (abbreviated as SAB). These rules allows us to study bulks that have twists and branching. We discuss certain cases in the SAB model with different number of bands, exhibiting several interesting physical properties. For every bulk there can be two sets of configurations: the orientable and the non-orientable configuration. The later exhibits several non-trivial physical properties like exact flat bands (exactly at particle hole symmetry level), zero energy states localised in the bulk, topological edge states etc. We then discuss a three band non-orientable SAB model which is easy to visualise and hence can be realized in experiments first. We also investigate the effects of disorder (both chiral symmetry preserving and breaking) in the non-orientable configurations hosting flat bands. We find for chiral symmetry preserving disorders, some of them (non-degenerate flat band) are robust to large disorders while others (degenerate flat band) exhibit an insulator to metal transition beyond certain disorder strength due to band gap closing as a result of the broadening of the zero energy states. For chiral symmetry breaking disorders, in both the cases the zero energy bulk states broaden and close the gap beyond certain critical disorder strength.

Theoretical and Experimental Analysis of Single-Arm Bimodal Plasmo-Photonic Refractive Index Sensors.

In this paper, we study both theoretically and experimentally the sensitivity of bimodal interferometric sensors where interference occurs between two plasmonic modes with different properties propagating in the same physical waveguide. In contrast to the well-known Mach-Zehnder interferometric (MZI) sensor, we show for the first time that the sensitivity of the bimodal sensor is independent of the sensing area length. This is validated by applying the theory to an integrated plasmo-photonic bimodal sensor that comprises an aluminum (Al) plasmonic stripe waveguide co-integrated between two accessible SU-8 photonic waveguides. A series of such bimodal sensors utilizing plasmonic stripes of different lengths were numerically simulated, demonstrating bulk refractive index (RI) sensitivities around 5700 nm/RIU for all sensor variants, confirming the theoretical results. The theoretical and numerical results were also validated experimentally through chip-level RI sensing experiments on three fabricated SU-8/Al bimodal sensors with plasmonic sensing lengths of 50, 75, and 100 µm. The obtained experimental RI sensitivities were found to be very close and equal to 4464, 4386, and 4362 nm/RIU, respectively, confirming that the sensing length has no effect on the bimodal sensor sensitivity. The above outcome alleviates the design and optical loss constraints, paving the way for more compact and powerful sensors that can achieve high sensitivity values at ultra-short sensing lengths.

Su(Hw) interacts with Combgap to establish long-range chromatin contacts.

BACKGROUND: Insulator-binding proteins (IBPs) play a critical role in genome architecture by forming and maintaining contact domains. While the involvement of several IBPs in organising chromatin architecture in Drosophila has been described, the specific contribution of the Suppressor of Hairy wings (Su(Hw)) insulator-binding protein to genome topology remains unclear. RESULTS: In this study, we provide evidence for the existence of long-range interactions between chromatin bound Su(Hw) and Combgap, which was first characterised as Polycomb response elements binding protein. Loss of Su(Hw) binding to chromatin results in the disappearance of Su(Hw)-Combgap long-range interactions and in a decrease in spatial self-interactions among a subset of Su(Hw)-bound genome sites. Our findings suggest that Su(Hw)-Combgap long-range interactions are associated with active chromatin rather than Polycomb-directed repression. Furthermore, we observe that the majority of transcription start sites that are down-regulated upon loss of Su(Hw) binding to chromatin are located within 2 kb of Combgap peaks and exhibit Su(Hw)-dependent changes in Combgap and transcriptional regulators' binding. CONCLUSIONS: This study demonstrates that Su(Hw) insulator binding protein can form long-range interactions with Combgap, Polycomb response elements binding protein, and that these interactions are associated with active chromatin factors rather than with Polycomb dependent repression.

Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway.

AIM: To explore the effects of hepatocyte growth factor (HGF) on retinal pigment epithelium (RPE) cell behaviors. METHODS: The human adult retinal pigment epithelial cell line-19 (ARPE-19) were treated by HGF or mesenchymal-epithelial transition factor (MET) inhibitor SU11274 in vitro. Cell viability was detected by a Cell Counting Kit-8 assay. Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay, respectively. The expression levels of MET, phosphorylated MET, protein kinase B (AKT), and phosphorylated AKT proteins were determined by Western blot assay. The MET and phosphorylated MET proteins were also determined by immunofluorescence assay. RESULTS: HGF increased ARPE-19 cells' viability, proliferation and migration, and induced an increase of phosphorylated MET and phosphorylated AKT proteins. SU11274 significantly reduced cell viability, proliferation, and migration and decreased the expression of MET and AKT proteins. SU11274 suppressed HGF-induced increase of viability, proliferation, and migration in ARPE-19 cells. Additionally, SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins. CONCLUSION: HGF enhances cellular viability, proliferation, and migration in RPE cells through the MET/AKT signaling pathway, whereas this enhancement is suppressed by the MET inhibitor SU11274. HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

A SU6668 pure nanoparticle-based eyedrops: toward its high drug Accumulation and Long-time treatment for corneal neovascularization.

Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.

Development of a New Model System to Study Long-Distance Interactions Supported by Architectural Proteins.

Chromatin architecture is critical for the temporal and tissue-specific activation of genes that determine eukaryotic development. The functional interaction between enhancers and promoters is controlled by insulators and tethering elements that support specific long-distance interactions. However, the mechanisms of the formation and maintenance of long-range interactions between genome regulatory elements remain poorly understood, primarily due to the lack of convenient model systems. Drosophila became the first model organism in which architectural proteins that determine the activity of insulators were described. In Drosophila, one of the best-studied DNA-binding architectural proteins, Su(Hw), forms a complex with Mod(mdg4)-67.2 and CP190 proteins. Using a combination of CRISPR/Cas9 genome editing and attP-dependent integration technologies, we created a model system in which the promoters and enhancers of two reporter genes are separated by 28 kb. In this case, enhancers effectively stimulate reporter gene promoters in cis and trans only in the presence of artificial Su(Hw) binding sites (SBS), in both constructs. The expression of the mutant Su(Hw) protein, which cannot interact with CP190, and the mutation inactivating Mod(mdg4)-67.2, lead to the complete loss or significant weakening of enhancer-promoter interactions, respectively. The results indicate that the new model system effectively identifies the role of individual subunits of architectural protein complexes in forming and maintaining specific long-distance interactions in the D. melanogaster model.

Impact of Interactions between Su(Hw)-Dependent Insulators on the Transvection Effect in Drosophila melanogaster.

Transvection is a phenomenon of interallelic communication in which enhancers can activate a specific promoter located on a homologous chromosome. Insulators play a significant role in ensuring functional interactions between enhancers and promoters. In the presented work, we created a model where two or three copies of the insulator are located next to enhancers and promoters localized on homologous chromosomes. Using the Su(Hw) insulator as a model, we showed that the functional interaction between a pair of insulators promotes enhancer-promoter trans-interactions. The interaction between the three insulators, on the contrary, can lead to the formation of chromatin loops that sterically hinder the full enhancer-promoter interaction. The results of the work suggest the participation of insulators in the regulation of homologous chromosome pairing and in communication between distant genomic loci.

Bombyx moriSuppressor of Hairless is involved in the regulation of the silkworm cell cycle and endoreplication of the silk glands.

The Notch signaling pathway is important in cell cycle regulation and cell proliferation. The transcriptional repressor Suppressor of Hairless [Su(H)] is a molecular switch for downstream target genes of the Notch signaling pathway but the regulatory mechanism of the Su(H) gene in the cell cycle is unclear. We determined the function of the Notch signaling pathway and Bombyx mori Su(H) [BmSu(H)] in the regulation of the silkworm cell cycle. Inhibition of Notch signaling promoted the replication of DNA in silkworm gland cells and expression of the BmSu(H) gene was significantly reduced. Overexpression of the BmSu(H) gene inhibited DNA replication and cell proliferation of silkworm cells, whereas knockout of the BmSu(H) gene promoted DNA replication and cell proliferation. Knockout of the BmSu(H) in silkworms improved the efficiency of silk gland cell endoreplication and increased important economic traits. We demonstrated that BmSu(H) protein can directly bind to the promoters of BmCyclinA, BmCyclinE and BmCDK1 genes, inhibiting or promoting their transcription at the cell and individual level. This study identified molecular targets for genetic improvement of the silkworm and also provided insights into the regulatory mechanism of the cell cycle.

SU-101 for the removal of pharmaceutical active compounds by the combination of adsorption/photocatalytic processes.

Pharmaceutical active compounds (PhACs) are some of the most recalcitrant water pollutants causing undesired environmental and human effects. In absence of adapted decontamination technologies, there is an urgent need to develop efficient and sustainable alternatives for water remediation. Metal-organic frameworks (MOFs) have recently emerged as promising candidates for adsorbing contaminants as well as providing photoactive sites, as they possess exceptional porosity and chemical versatility. To date, the reported studies using MOFs in water remediation have been mainly focused on the removal of a single type of PhACs and rarely on the combined elimination of PhACs mixtures. Herein, the eco-friendly bismuth-based MOF, SU-101, has been originally proposed as an efficient adsorbent-photocatalyst for the elimination of a mixture of three challenging persistent PhACs, frequently detected in wastewater and surface water in ng L-1 to mg·L-1 concentrations: the antibiotic sulfamethazine (SMT), the anti-inflammatory diclofenac (DCF), and the antihypertensive atenolol (At). Adsorption experiments of the mixture revealed that SU-101 exhibited a great adsorption capacity towards At, resulting in an almost complete removal (94.1 ± 0.8% for combined adsorption) in only 5 h. Also, SU-101 demonstrated a remarkable photocatalytic activity under visible light to simultaneously degrade DCF and SMT (99.6 ± 0.4% and 89.2 ± 1.4%, respectively). In addition, MOF-contaminant interactions, the photocatalytic mechanism and degradation pathways were investigated, also assessing the toxicity of the resulting degradation products. Even further, recycling and regeneration studies were performed, demonstrating its efficient reuse for 4 consecutive cycles without further treatment, and its subsequent successful regeneration by simply washing the material with a NaCl solution.

Willingness to Pay (WTP) for Newer Treatment Options for Diabetes: A Study Among Patients at a Tertiary Care Centre.

Introduction Type 2 diabetes mellitus (T2DM) poses a substantial burden globally and particularly in India, affecting health, finances, and overall quality of life. The management of this condition relies on lifestyle modifications and advanced pharmacological interventions, with emerging drugs showing promise in areas such as administration, side effects, efficacy, and cardiovascular benefits. However, their market penetration is hindered by high costs. Understanding the target population's expectations and willingness to pay (WTP) for these drugs is crucial. WTP, a key concept in behavioral science, reflects the maximum price consumers are willing to pay for a product, aiding in healthcare cost-effectiveness evaluations. Despite its relevance, only one WTP study has been conducted in the Indian context for diabetes. This study explores WTP for two novel drugs: oral semaglutide and icodec (weekly insulin). Material and methods This observational study, conducted in a diabetes specialty clinic and telemedicine facility in All India Institute of Medical Sciences, Bhopal, India, involved adults (18-80 years) diagnosed with T2DM. Data collection adhered to ethical guidelines, and participants provided written informed consent. Face-to-face interviews were employed to gather socio-economic, demographic, and medical details. Participants estimated their WTP for oral semaglutide and weekly insulin, considering reference ranges for existing antidiabetic treatments. Statistical analyses, including t-tests and analysis of variance, explored sociodemographic and clinical factors influencing WTP. Results Of 105 approached patients, 87 (74.3%) participated. The majority were males (55.2%) with an average age of 57.2 years. The average WTP for oral semaglutide was INR 9.35±5.66 per pill, significantly lower than its market price (INR 315). For weekly insulin (icodec), the WTP was INR 157.25±112.60 per dose. Subgroup analyses revealed no significant correlations based on sociodemographic or clinical parameters. Conclusion This study demonstrated the feasibility of WTP assessments in an Indian outpatient setting, revealing a substantial cost disparity between patients' WTP for oral semaglutide and its market price. The findings underscore the importance of considering WTP in introducing new diabetes medications in India, offering valuable insights for healthcare decision-makers and developers.

The Recognition Pathway of the SARS-CoV-2 Spike Receptor-Binding Domain to Human Angiotensin-Converting Enzyme 2.

COVID-19 caused by SARS-CoV-2 has spread around the world. The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 is a critical component that directly interacts with host ACE2. Here, we simulate the ACE2 recognition processes of RBD of the WT, Delta, and OmicronBA.2 variants using our recently developed supervised Gaussian accelerated molecular dynamics (Su-GaMD) approach. We show that RBD recognizes ACE2 through three contact regions (regions I, II, and III), which aligns well with the anchor-locker mechanism. The higher binding free energy in State d of the RBDOmicronBA.2-ACE2 system correlates well with the increased infectivity of OmicronBA.2 in comparison with other variants. For RBDDelta, the T478K mutation affects the first step of recognition, while the L452R mutation, through its nearby Y449, affects the RBDDelta-ACE2 binding in the last step of recognition. For RBDOmicronBA.2, the E484A mutation affects the first step of recognition, the Q493R, N501Y, and Y505H mutations affect the binding free energy in the last step of recognition, mutations in the contact regions affect the recognition directly, and other mutations indirectly affect recognition through dynamic correlations with the contact regions. These results provide theoretical insights for RBD-ACE2 recognition and may facilitate drug design against SARS-CoV-2.

Antioxidant and Antibacterial Properties of 1,3-Dihydroxy-,2', 2'-Dimethylpyrano-(5,6)-Xanthone from Streptomyces sp. SU84.

<b>Background and Objective:</b> The SU84 was isolated from the rhizosphere of <i>Curcuma longa</i> and identified to be <i>Streptomyces</i> sp. via analysis of its 16S rDNA sequence, chemotaxonomy and morphology. This study aimed to isolate major compounds from the extract culture of strain SU84 and evaluate their antibacterial activity. <b>Materials and Methods:</b> The TLC and silica gel column chromatography were used to purify major compounds, elucidate 1,3-dihydroxy-,2',2'-dimethylpyrano-(5,6)-xanthone (compound <b>1</b>) and lupeol (compound <b>2</b>) using mass spectrometry and nuclear magnetic resonance. One new chemical, compound <b>1</b>, was first isolated from microbial sources. Antibacterial, antioxidant and cytotoxic properties of these compounds were carried out. <b>Results:</b> Various bioassays showed that compound <b>1</b> displayed antibacterial property against Gram-positive bacteria, with a minimum inhibitory concentration of 8-32 µg/mL and minimum bactericidal concentration of 32-128 µg/mL. In addition, the purified compounds were tested against normal cell lines using tetrazolium assay. The results did not show cytotoxic property against L929 and Vero cells, with IC₅₀ values of >512.00 µg/mL. Compounds <b>1</b> and <b>2</b> have also antioxidant properties, with IC₅₀ values of 16.67±7.48 and 38.86±8.45 µg/mL, respectively. <b>Conclusion:</b> The findings suggested that compounds of <i>Streptomyces</i> sp. SU84 displayed antibacterial and antioxidant properties without cytotoxic activity. Extensive studies of compound <b>1</b> may be useful for the advancement of improved methods for avoidance, control and management of bacterial infections and metabolic-related free radical contribution.

Unilateral Lung Removal in Combination with Monocrotaline or SU5416 in Rodents: A Reliable Model to Mimic the Pathology of the Human Pulmonary Hypertension.

Pulmonary hypertension (PH) is a chronic and progressive disorder characterized by elevated mean pulmonary arterial pressure, pulmonary vascular remodeling, and the development of concentric laminar intimal fibrosis with plexiform lesions. While rodent models have been developed to study PH, they have certain deficiencies and do not entirely replicate the human disease due to the heterogeneity of PH pathology. Therefore, combined models are necessary to study PH. Recent studies have shown that altered pulmonary blood flow is a significant trigger in the development of vascular remodeling and neointimal lesions. One of the most promising rodent models for increased pulmonary flow is the combination of unilateral left pneumonectomy with a "second hit" of monocrotaline (MCT) or SU5416. The removal of one lung in this model forces blood to circulate only in the other lung and induces increased and turbulent pulmonary blood flow. This increased vascular flow leads to progressive remodeling and occlusion of small pulmonary arteries. The second hit by MCT or SU5416 leads to endothelial cell dysfunction, resulting in severe PH and the development of plexiform arteriopathy.

Association between nutritional risk status and both diaphragmatic dysfunction and diaphragm atrophy in medical intensive care unit patients / Asociación entre el estado de riesgo nutricional y la disfunción diafragmática y la atrofi a del diafragma en pacientes de la unidad de cuidados intensivos médicos

Aim: critical illness often leads to malnutrition and diaphragmatic dysfunction (DD), common in intensive care units (ICU). Ultrasonography (US) is a potent tool for detecting DD. This study examines the connection between malnutrition risk and DD in ICU patients using ultrasonographic diaphragm measurements in medical ICU patients. Methods: we assessed nutritional risk using risk screening tools and mid-upper arm circumference measurements (MUAC). Diaphragm atrophy (DA) and DD were evaluated by measuring diaphragmatic excursion (DE), thickness, and thickening fraction (TF) by US. We then compared these diaphragmatic measurements in patients based on their nutritional risk scores. Results: of the fifty patients studied, 54 % to 78 % were at risk of malnutrition, 28 % exhibited diaphragm atrophy (DA), and 24 % showed DD upon ICU admission. Malnutrition risk diagnosed by all nutritional risk screening tools was significantly more frequent in patients with DD, while diagnosed by MUAC was considerably higher in patients with DA. A total of 16 patients (32 %) died during their ICU stay, with DD, DA, and malnutrition risks (as identified by the mNUTRIC Score) being more prevalent among non-survivors (p < 0.05). Malnutrition risk (as determined by the mNUTRIC Score) was an independent risk factor for DD [OR (95 % CI): 6.6 (1.3-34), p = 0.03]. Conclusion: malnutrition risk may be significantly associated with DD and DA in medical ICU patients upon ICU admission.(AU)

Objetivo: las enfermedades graves a menudo conducen a desnutrición y disfunción diafragmática (DD), comunes en las unidades de cuidados intensivos (UCI). La ultrasonografía (US) es una herramienta poderosa para detectar la DD. Este estudio examina la conexión entre riesgo de desnutrición y DD en pacientes de UCI utilizando mediciones ultrasonográficas del diafragma.Métodos: evaluamos el riesgo nutricional utilizando herramientas de evaluación de riesgos y mediciones de la circunferencia del brazo en su punto medio superior (MUAC). La atrofia del diafragma (DA) y la DD se evaluaron midiendo la excursión diafragmática (DE), el grosor y la fracción de engrosamiento (TF) por ecografía. Luego, comparamos estas mediciones diafragmáticas en pacientes según sus puntuaciones de riesgo nutricional. Resultados: de los cincuenta pacientes estudiados, entre el 54 % y el 78 % estaban en riesgo de desnutrición, el 28 % presentaban atrofia del diafragma (DA) y el 24 % mostraban DD al ingreso en la UCI. El riesgo de desnutrición diagnosticado por todas las herramientas de evaluación del riesgo nutricional fue significativamente más frecuente en los pacientes con DD, mientras que el diagnosticado por el MUAC fue considerablemente mayor en los pacientes con DA. Un total de 16 pacientes (32 %) fallecieron durante su estancia en la UCI, siendo la DD, la DA y los riesgos de desnutrición (según lo identificado por la puntuación mNUTRIC) más prevalentes entre los no sobrevivientes (p < 0,05). El riesgo de desnutrición (según lo determinado por la puntuación mNUTRIC) fue un factor de riesgo independiente de la DD [OR (95 % CI): 6,6 (1,3-34), p = 0,03]. Conclusión: en este estudio se encontró una asociación significativa entre el riesgo de desnutrición y la disfunción diafragmática, así como con la atrofia diafragmática al ingreso en la UCI.(AU)

Construction of SU-102 for adsorption and photocatalytic synergistic removal of tetracycline.

Tetracycline (TC) is a significant group of broad-spectrum antibiotics that are frequently employed in medical health and animal husbandry. However, the problem of TC residues has been increasing globally with the large-scale production and widespread use, posing a serious threat to the human health and ecological environment. In this paper, a green plant-based MOF SU-102 was prepared, and the adsorption characteristics of SU-102 on TC were investigated. SU-102 was columnar crystal with considerable specific surface area and pore structure, and it could adsorb TC quickly and effectively. And compared to SU-102-a, the adsorption rate of TC by SU-102-b has increased by nearly four times. The adsorption reaction was a spontaneous, entropy-gaining, heat-absorbing process. The adsorption mechanisms between SU-102 and TC were π-π interaction and hydrogen bonding. In addition, SU-102 also had considerable photocatalytic properties, and its application in adsorbent desorption treatment effectively solved the problem of secondary pollution.

Dipeptidyl peptidase-4 inhibitors versus sulfonylureas on the top of metformin in patients with diabetes and acute myocardial infarction.

Background: Recent trials have shown that both the extent of glycated hemoglobin reduction and the duration of enhanced glycemic control are major factors that may affect cardiovascular outcome results. We aimed to investigate the impact of metformin (MET) combined with dipeptidyl peptidase-4 (DPP4) inhibitors or sulfonylureas (SU) on long-term clinical outcomes in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (DM). Methods: This study was a prospective cohort trial. From November 2011 to December 2015, a total of 13,104 AMI patients were consecutively enrolled from the Korea AMI registry-National Institutes of Health. The patients were divided into the MET + DPP4 inhibitors group and the MET + SU group. The primary endpoint, major adverse cardiac events (MACE), was defined as the composite of all-cause death, recurrent myocardial infarction (MI), and any repeat revascularization up to 3-year follow-up. To adjust baseline potential confounders, an inverse probability weighting (IPTW) analysis was performed. Results: Baseline well-matched two groups were generated (the MET + DPP4 inhibitors group, n=468 and the MET + SU group, n=468). During 3-year clinical follow-up, the cumulative incidence of MACE between the two groups was not significantly different after adjustment (16.8% for MET + DPP4 inhibitors group vs. 19.4% for MET + SU group, P=0.302). However, the MET + DPP4 inhibitors group was associated with reduced risk of MI [1.3% vs. 4.9%; hazard ratio (HR): 0.228, 95% confidence interval (CI): 0.090-0.580, P=0.001] than the MET + SU group. Conclusions: In patients with AMI and type 2 DM, the use of MET combined with DPP4 inhibitors was associated with reduced incidence of recurrent MI than MET combined with SU during 3-year follow-up.

Enhancing Manufacturability of SU-8 Piezoelectric Composite Films for Microsystem Applications.

Piezoelectric thin films are extensively used as sensing or actuating layers in various micro-electromechanical systems (MEMS) applications. However, most piezoelectrics are stiff ceramics, and current polymer piezoelectrics are not compatible with microfabrication due to their low Curie Temperature. Recent polymer-composite piezoelectrics have gained interest but can be difficult to pattern. Photodefinable piezoelectric films could resolve these challenges by reducing the manufacturability steps by eliminating the etching process. But they typically have poor resolution and thickness properties. This study explores methods of enhancing the manufacturability of piezoelectric composite films by optimizing the process parameters and synthesis of SU-8 piezo-composite materials. Piezoelectric ceramic powders (barium titanate (BTO) and lead zirconate titanate (PZT)) were integrated into SU-8, a negative epoxy-based photoresist, to produce high-resolution composites in a non-cleanroom environment. I-line (365 nm) light was used to enhance resolution compared to broadband lithography. Two variations of SU-8 were prepared by thinning down SU-8 3050 and SU-8 3005. Different weight percentages of the piezoelectric powders were investigated: 5, 10, 15 and 20 wt.% along with varied photolithography processing parameters. The composites' transmittance properties were characterized using UV-Vis spectroscopy and the films' crystallinity was determined using X-ray diffraction (XRD). The 0-3 SU-8/piezo composites demonstrated resolutions < 2 µm while maintaining bulk piezoelectric coefficients d33 > 5 pm V-1. The films were developed with thicknesses >10 µm. Stacked layers were achieved and demonstrated significantly higher d33 properties.

Fabrication of SU-8 polymer micro/nanoscale nozzle by hot embossing method.

Electrohydrodynamic-jet printing (E-jet printing) is a direct-writing technology for manufacturing micro-nano devices. To further reduce the inner diameter of the nozzle to improve the printing resolution, a large-scale manufacturing method of SU-8 polymer micro/nanoscale nozzle by means of a process combining UV exposure and hot embossing was proposed. To improve the adhesive strength between the UV mask and SU-8, the influence of the oxygen plasma treatment parameters on the water contact angles of the UV mask was analyzed. The effect of hot embossing time and temperature on the replication precision was studied. The influence of UV exposure parameters and thermal bonding parameters on the micro and nanochannel pattern was investigated. The SU-8 polymer nozzles with 188 ± 3 nm wide and 104 ± 2 nm deep nanochannels were successfully fabricated, and the replication precision can reach to 98.5%. The proposed manufacturing method of SU-8 polymer nozzles in this study will significantly advance the research on the transport properties of nanoscale channels in E-jet nozzles and facilitate further advancements in E-jet based applications.

Association between nutritional risk status and both diaphragmatic dysfunction and diaphragm atrophy in medical intensive care unit patients.

Introduction: Aim: critical illness often leads to malnutrition and diaphragmatic dysfunction (DD), common in intensive care units (ICU). Ultrasonography (US) is a potent tool for detecting DD. This study examines the connection between malnutrition risk and DD in ICU patients using ultrasonographic diaphragm measurements in medical ICU patients. Methods: we assessed nutritional risk using risk screening tools and mid-upper arm circumference measurements (MUAC). Diaphragm atrophy (DA) and DD were evaluated by measuring diaphragmatic excursion (DE), thickness, and thickening fraction (TF) by US. We then compared these diaphragmatic measurements in patients based on their nutritional risk scores. Results: of the fifty patients studied, 54 % to 78 % were at risk of malnutrition, 28 % exhibited diaphragm atrophy (DA), and 24 % showed DD upon ICU admission. Malnutrition risk diagnosed by all nutritional risk screening tools was significantly more frequent in patients with DD, while diagnosed by MUAC was considerably higher in patients with DA. A total of 16 patients (32 %) died during their ICU stay, with DD, DA, and malnutrition risks (as identified by the mNUTRIC Score) being more prevalent among non-survivors (p < 0.05). Malnutrition risk (as determined by the mNUTRIC Score) was an independent risk factor for DD [OR (95 % CI): 6.6 (1.3-34), p = 0.03]. Conclusion: malnutrition risk may be significantly associated with DD and DA in medical ICU patients upon ICU admission.

Introducción: Objetivo: las enfermedades graves a menudo conducen a desnutrición y disfunción diafragmática (DD), comunes en las unidades de cuidados intensivos (UCI). La ultrasonografía (US) es una herramienta poderosa para detectar la DD. Este estudio examina la conexión entre riesgo de desnutrición y DD en pacientes de UCI utilizando mediciones ultrasonográficas del diafragma. Métodos: evaluamos el riesgo nutricional utilizando herramientas de evaluación de riesgos y mediciones de la circunferencia del brazo en su punto medio superior (MUAC). La atrofia del diafragma (DA) y la DD se evaluaron midiendo la excursión diafragmática (DE), el grosor y la fracción de engrosamiento (TF) por ecografía. Luego, comparamos estas mediciones diafragmáticas en pacientes según sus puntuaciones de riesgo nutricional. Resultados: de los cincuenta pacientes estudiados, entre el 54 % y el 78 % estaban en riesgo de desnutrición, el 28 % presentaban atrofia del diafragma (DA) y el 24 % mostraban DD al ingreso en la UCI. El riesgo de desnutrición diagnosticado por todas las herramientas de evaluación del riesgo nutricional fue significativamente más frecuente en los pacientes con DD, mientras que el diagnosticado por el MUAC fue considerablemente mayor en los pacientes con DA. Un total de 16 pacientes (32 %) fallecieron durante su estancia en la UCI, siendo la DD, la DA y los riesgos de desnutrición (según lo identificado por la puntuación mNUTRIC) más prevalentes entre los no sobrevivientes (p < 0,05). El riesgo de desnutrición (según lo determinado por la puntuación mNUTRIC) fue un factor de riesgo independiente de la DD [OR (95 % CI): 6,6 (1,3-34), p = 0,03]. Conclusión: en este estudio se encontró una asociación significativa entre el riesgo de desnutrición y la disfunción diafragmática, así como con la atrofia diafragmática al ingreso en la UCI.