Hybrid Design Research Articles

Novel molecular hybrids of EGCG and quinoxaline: Potent multi-targeting antidiabetic agents that inhibit α-glucosidase, α-amylase, and oxidative stress

Diabetes mellitus is a multifactorial disease and its effective therapy often demands several drugs with different modes of action. Herein, we report a rational design and synthesis of multi-targeting novel molecular hybrids comprised of EGCG and quinoxaline derivatives that can effectively inhibit α-glucosidase, α-amylase as well as control oxidative stress by scavenging ROS. The hybrids showed superior inhibition of α-glucosidase along with similar α-amylase inhibition as compared to standard drug, acarbose. Most potent compound, 15c showed an IC50 of 0.50 μM (IC50 of acarbose 190 μM) against α-glucosidase. Kinetics studies with 15c revealed a competitive inhibition against α-glucosidase. Binding affinity of 15c (−9.5 kcal/mol) towards α-glucosidase was significantly higher than acarbose (−7.7 kcal/mol). 15c exhibited remarkably high antioxidant activity (IC50 = 18.84 μM), much better than vitamin C (IC50 = 33.04 μM). Of note, acarbose shows no antioxidant activity. Furthermore, α-amylase activity was effectively inhibited by 15c with an IC50 value of 16.35 μM. No cytotoxicity was observed for 15c (up to 40 μM) in MCF-7 cells. Taken together, we report a series of multi-targeting molecular hybrids capable of inhibiting carbohydrate hydrolysing enzymes as well as reducing oxidative stress, thus representing an advancement towards effective and novel therapeutic approaches for diabetes.

Design and mechanical performance of nature-inspired novel hybrid triply periodic minimal surface lattice structures fabricated using material extrusion

The materials found in nature often exhibit intriguing characteristics due to multiple mor- phologies that are architecture and integrated at different length scales. On the other hand, most of the engineered cellular lattice structures possess a less-sophisticated, uniform, and one type of morphology that may not be ideal and optimized. Therefore, the engineered materials possess multiple morphologies/hybrid lattices can exhibit higher performance and advantages to achieve desired properties. In this work, hybrid lattice structures are designed by incorporating surface-based triply periodic minimal surface (TPMS) structures that are constructed using implicit equations. Six samples were designed that include four hybrid (Diamond, Gyroid, Lidinoid, Split P are joined and hybridized linearly in a single sample) and two uniform morphology samples composed of Gyroid, and Diamond TPMS structures. The challenges related to interfaces while joining different morphologies in hybrid samples were addressed properly. For quasi-static compression tests, three specimens for each sample were additively manufactured using PLA material. Mechanical performance in terms of strength, stiffness, energy absorption and failure are studied using experimental and finite element analysis methods. The results show that hybrid HS2 and Diamond structures performance is almost similar at higher strain rates; however, the deformation behavior significantly varied. The deformation mechanics of hybrid structure is greatly different from uniform morphology counterparts. Structures with better connectivity almost deform together and it highly affects the post-yield response of the structure. Uniform morphology structures absorbed energy nearly at a constant stress level; whereas, all hybrid structures possess progressive mode of energy absorption. The hybrid structure HS2 possesses highest specific energy absorption among all structures. Thus, hybrid structures are crucial when used for energy absorption application with a progressive deformation mechanics such as footwear, blast, impact, crashworthiness, and ballistic protection applications.

Spectral and Temporal Manipulation of Ultralong Phosphorescence Based on Melt‐Quenched Glassy Metal–Organic Complexes for Multi‐Mode Photonic Functions

AbstractTransparent glasses are ideal and robust hosts for a range of emission centers, while the simultaneous manipulation of the temporal and spectral characteristics of emission remains a tremendous challenge for inorganic glasses. Here, the development and functionalization of melt‐quenched transparent coordinate polymer glasses with a tailorable ultralong room‐temperature phosphorescence are demonstrated. Dynamic modulation of the phosphorescence is achieved by utilization of the high molecular rigidity and manipulation of the spin‐orbital coupling effects within the glass systems. By introducing dye molecules into the glasses, Phosphorescence resonance energy transfer from the glass matrix to the dye molecules is exploited and controllable multicolor long‐lived luminescence is demonstrated. Further design of the component and concentration of the encapsulated dyes allows for wavelength‐tunable long‐lived delayed fluorescence via an efficient delayed sensitization process, featuring a tunable emission spectrum covering a wide range from 520 to 630 nm. Leveraging the multiple spectral tuning channels of the hybrid glass, multi‐mode optical information storage, and dynamic anti‐counterfeiting applications are further demonstrated. This work provides a new hybrid material platform and design methodology for realizing lifetime‐adjustable and wavelength‐tunable long‐lived luminescence, which can find wide applications in time‐rsesolved information display, high‐density information storage, and dynamic anti‐counterfeiting.

A hybrid bio-inspired sandwich structures for high strain rate energy absorption applications

Due to its advantages in terms of enhancing the performance of structures in the desired applications, the bio-inspired design approach has recently attracted the interest of researchers in a number of engineering disciplines. A hybrid bio-inspired design is suggested for the sandwich structures to absorb the energy of the blast loads in the current study. The sandwich structure's core, which often has a regular grid pattern resembling a honeycomb structure, is crucial to how well the panel absorbs energy. In order to achieve the best results, we first chose the structure of the core grid by taking into account potential 2D grids (polygons and multi-pointed stars) through Genetic Algorithm optimization. Next, we combined a bio-inspired bi-tubular thin-walled structure with the core grid to take advantage of its high energy absorption capacity. Finally, the performance of the suggested design is compared with four frequently implemented ones. The results show that the hybrid design has better energy absorption characteristics compared with the bionic and conventional designs presented in the literature.

‘The International Style’ multilingual three-dimensional grammar and hybrid designs

The present paper describes a multilingual shape grammar to recreate the work of three designers that preconized the ‘International Style’. This is a top-down three-dimensional formulation. Whilst most grammars are monolingual and univocal, this work creates a multilingual formulation within the same artistic movement. Typically, a grammar describes a family of design solutions. These are helpful mechanisms to describe patterns that can be used for analysis or design exploration. This multilingual three-dimensional parametric grammar allows the independent recreation of original designs from three designers and hybrid solutions. Shape grammar's difficult application can be linked to its evaluation process. The original contribution of the study lies in the use of quantitative and qualitative methods for grammar evaluation, using Principal Components Analysis and user questionnaires. The PCA provides a pragmatic analysis, and the questionnaires an intuitive reading. Together they corroborate the results which are discussed using hybrids that assist in delineating parametric spaces.

Study of Whole blood in Frontline Trauma (SWiFT): implementation study protocol

IntroductionUncontrolled bleeding is a major cause of death for patients with major trauma. Current transfusion practices vary, and there is uncertainty about the optimal strategy. Whole blood (WB) transfusion, which...

Phase III randomized trial of stereotactic ablative radiotherapy (SAbR) for oligometastatic advanced renal carcinoma (EA8211-SOAR).

TPS489 Background: Optimal strategies for managing oligometastatic renal cell carcinoma (RCC) are unclear. While systemic therapy is the accepted standard, Stereotactic Ablative Radiation (SAbR) is a promising alternative based on retrospective and limited prospective data1-3. SAbR may spare patients from systemic therapy toxicity, but progression of occult micrometastasis remains a concern. This prospective ECOG-ACRIN phase 3 randomized trial will compare SAbR to systemic therapy for oligometastatic RCC. Co-primary endpoints are overall survival (OS) and toxicity. Methods: Patients with RCC (any histology except for sarcomatoid) with an ECOG performance 0-2, International Metastatic RCC Database Consortium (IMDC) favorable and intermediate-risk, and 2-5 extracranial metastases are eligible. The exclusion criteria include prior systemic therapy (except for adjuvant therapy) and brain metastases. Patients with intact primary are eligible after definitive treatment of the primary site. Stratification factors include 1) number of metastases (2-3 vs 4-5), 2) histology (clear cell vs non-clear cell), 3) IMDC (0 vs 1-2), 4) prior adjuvant systemic therapy (yes vs no), and 5) time from treatment of primary disease (<1yr vs >1yr). Patients will be randomized to up front systemic therapy (the type of systemic therapy will be chosen at the discretion of the investigator) versus SAbR (and additional SAbR of up to a total of 6 metastasis while disease remains amenable) followed by systemic therapy. Co-primary endpoints are OS and toxicity (≥grade 3). Target accrual goal is 472 patients which will provide 85% power to test non-inferiority in OS from a non-inferiority hybrid design, assuming a null hazard ratio of 1.24 and alternative hazard ratio of 0.85. If it is concluded that SAbR arm has non-inferior OS, superiority in toxicity will be tested. Secondary endpoints include health-related quality of life (QOL) as measured with NFKSI-19 and EQ-5D-5L and progression free survival (PFS). Exploratory endpoints include PFS of 1st line systemic therapy, local control with SAbR and cost-effectiveness. The trial has been open for enrollment since September 2023.

Recent developments of hydroxamic acid hybrids as potential anti-breast cancer agents.

Histone deacetylase inhibitors not only possess favorable effects on modulating tumor microenvironment and host immune cells but also can reactivate the genes silenced due to deacetylation and chromatin condensation. Hydroxamic acid hybrids as promising histone deacetylase inhibitors have the potential to address drug resistance and reduce severe side effects associated with a single drug molecule due to their capacity to simultaneously modulate multiple targets in cancer cells. Accordingly, rational design of hydroxamic acid hybrids may provide valuable therapeutic interventions for the treatment of breast cancer. This review aimed to provide insights into the in vitro and in vivo anti-breast cancer therapeutic potential of hydroxamic acid hybrids, together with their mechanisms of action and structure-activity relationships, covering articles published from 2020 to the present.

Doxorubicin Conjugated γ-Globulin Functionalised Gold Nanoparticles: A pH-Responsive Bioinspired Nanoconjugate Approach for Advanced Chemotherapeutics.

Developing successful nanomedicine hinges on regulating nanoparticle surface interactions within biological systems, particularly in intravenous nanotherapeutics. We harnessed the surface interactions of gold nanoparticles (AuNPs) with serum proteins, incorporating a γ-globulin (γG) hard surface corona and chemically conjugating Doxorubicin to create an innovative hybrid anticancer nanobioconjugate, Dox-γG-AuNPs. γG (with an isoelectric point of ~7.2) enhances cellular uptake and exhibits pH-sensitive behaviour, favouring targeted cancer cell drug delivery. In cell line studies, Dox-γG-AuNPs demonstrated a 10-fold higher cytotoxic potency compared to equivalent doxorubicin concentrations, with drug release favoured at pH 5.5 due to the γ-globulin corona's inherent pH sensitivity. This bioinspired approach presents a novel strategy for designing hybrid anticancer therapeutics. Our study also explored the intricacies of the p53-mediated ROS pathway's role in regulating cell fate, including apoptosis and necrosis, in response to these treatments. The pathway's delicate balance of ROS emerged as a critical determinant, warranting further investigation to elucidate its mechanisms and implications. Overall, leveraging the robust γ-globulin protein corona on AuNPs enhances biostability in harsh serum conditions, augments anticancer potential within pH-sensitive environments, and opens promising avenues for bioinspired drug delivery and the design of novel anticancer hybrids with precise targeting capabilities.

Study Protocol for the Healing Opioid Misuse and Pain Through Engagement Trial: Integrated Treatment for Individuals With Co-occurring Chronic Pain and Opioid Use Disorder.

Chronic pain and opioid use disorder (OUD) are public health crises and their co-occurrence has led to further complications and public health impacts. Provision of treatments for comorbid chronic pain and OUD is paramount to address these public health crises. Medications for OUD (MOUD) are gold standard treatments for OUD that have also demonstrated benefit in pain management. However, clinics that provide MOUD for chronic pain or OUD often lack behavioral treatments to address the challenges experienced by individuals with both conditions. Developing and implementing a behavioral treatment that complements MOUD may better equip clinics to provide comprehensive care to the growing proportion of clients who present with comorbid chronic pain and OUD. In the Healing Opioid misuse and Pain through Engagement (HOPE) Trial, we are using an effectiveness-implementation hybrid design to examine the benefits of an integrated behavioral treatment and to determine the feasibility of implementing the integrated treatment into clinics that provide MOUD. The treatment integrated 2 evidence-based treatments-Acceptance and Commitment Therapy and Mindfulness-Based Relapse Prevention-to target the emotional, behavioral, and physiological sequelae of OUD and chronic pain. Implementation feasibility will include assessing changes in implementation readiness and identifying facilitators and barriers to implementing the integrated treatment among all personnel employed in clinics that provide MOUD. This commentary offers an overview of the study and design and details adaptations we made to our study protocol, based largely on clinic personnel time constraints and variable clinic procedures during the COVID-19 pandemic.

Battery Operated Hybrid Vehicle/Systems

By the use of Battery operated Hybrid vehicle/system helps in reducing the pollution/emission and also reduces the consumption of fossil fuel (petrol, diesel, CNG etc.) Without compromising its performance, may leads to this hybrid design more economical as well as more ecofriendly when compare it with convention vehicles (fossil fuel operated IC engine Vehicles). The main advantages of using hybrid vehicle is flexibility in choosing any two engines it may be either Petrol engine with electric motor/generator, diesel engine with electric motor /generator etc. The traction battery used in Battery operated hybrid vehicle is either charge by using renewable energy sources or by using IC engine provide in combination with its.

Morphology design and electronic configuration of MoSe2 anchored on TiO2 nanospheres for high energy density sodium-ion half/full batteries

Molybdenum selenide (MoSe2) has shown potential sodium storage properties due to its large layer spacing (0.646 nm) and high theoretical capacity and narrow band gap. However, as the anode material of sodium ion batteries (SIBs), the MoSe2’s performance is not ideal, especially due to the layer agglomeration and stacking caused by volume expansion and low intrinsic conductivity. Hence, morphology design and electronic configuration of MoSe2 is proposed via building MoSe2 nanosheets and auxiliary sulfur doping on the surface of the TiO2 hollow nanosphere (S-MoSe2@TiO2). The hierarchical shaped S-MoSe2@TiO2 effectively overcomes the shortcomings of high surface energy and weak interlayer van der Waals force of MoSe2. As anode for SIBs, S-MoSe2@TiO2 delivers enhanced cycling life and rate capability (308 mAh/g at 10 A/g after 1000 cycles) with the comparison of MoSe2@TiO2 or pure MoSe2 and TiO2. Such excellent sodium storage performance is due to the fast diffusion kinetics of Na+. When it is applied in sodium ion full batteries, the S-MoSe2@TiO2 anode based cell can reach a high energy density of 187.8 W h kg−1 at 148.3 W kg−1. The design of the new MoSe2-based hybrid provides a novel scheme for the preparation of advanced anode in SIBs.

Feasibility of early digital health rehabilitation after cardiac surgery in the elderly: a qualitative study.

Increasing numbers of elderly patients experience prolonged decreased functional capacity and impaired quality of life after seemingly successful cardiac surgery. After discharge from hospital, these patients experience a substantial gap in care until centre-based cardiac rehabilitation commences. They may benefit from immediate coaching by means of mobile health technology to overcome psychological and physiological barriers to physical activity. The aim of this study was to explore the usability, acceptability, and relevance of a mobile health application designed to support remote exercise-based cardiac rehabilitation of elderly patients early after cardiac surgery from the perspective of patients, their relatives, and physiotherapists. We adapted a home-based mobile health application for use by elderly patients early after cardiac surgery. Semi-structured dyadic interviews were conducted with a purposive sample of patients (n = 9), their spouses (n = 5), and physiotherapists (n = 2) following two weeks of the intervention. The transcribed interviews were analysed thematically. Three themes were identified: 1) creating an individual fit by tailoring the intervention; 2) prioritizing communication and collaboration; and 3) interacting with the mobile health application. Overall, the findings indicate that the mobile health intervention has the potential to promote engagement, responsibility, and motivation among elderly patients to exercise early after surgery. However, the intervention can also be a burden on patients and their relatives when roles and responsibilities are unclear. The mobile health intervention showed potential to bridge the intervention gap after cardiac surgery, as well as in fostering engagement, responsibility, and motivation for physical activity among elderly individuals. Nevertheless, our findings emphasize the necessity of tailoring the intervention to accommodate individual vulnerabilities and capabilities. The intervention may be improved by addressing a number of organizational and communicational issues. Adaptions should be made according to the barriers and facilitators identified in this study prior to testing the effectiveness of the intervention on a larger scale. Future research should focus on the implementation of a hybrid design that supplements or complements face-to-face and centre-based cardiac rehabilitation. Danish Data Protection Agency, Central Denmark Region (1-16-02-193-22, 11 August 2022).

Design and Analysis of Solar/Wind Power Electronics Converters

The primary objective of this paper is to present the design and analysis of a power converter for a hybrid solar/wind micro grid energy conversion system. The power converter can transfer the power from a wind generator and photovoltaic panels and improve the safety and stability of hybrid micro grid systems. This micro grid system consists of Permanent Magnet Synchronous Generator (PMSG), a full wave AC-DC bridge rectifier, a DC-DC boost converter, a bidirectional DC-DC converter, and a full wave bridge DC-AC inverter. The wind generator and the photovoltaic panels are used as the primary power sources of the system, and a battery is used for energy storage and to compensate for the irregularity of the power sources. This paper also presents the structure of the rectifier stage for the power conversion system. This structure provides two energy sources simultaneously yet independently, according to their respective availability. Analysis for the power conversion system will be discussed in this paper and will give a design and analysis plan for hybrid wind/solar converter circuit. The power converter can transfer the power from a wind generator and photovoltaic panel. The wind generator and the photovoltaic panel are used as the primary power sources of the system, and a battery is used for energy storage and to compensate for the irregularity of the power sources. This paper also presents the structure of the beginning rectifier stage for the hybrid wind- solar energy power conversion system. This structure thereby provides two energy sources simultaneously yet independently, according to their respective availability. Analysis for the power conversion system will be discussed in this paper and will give a design and analysis plan for hybrid wind/solar converter circuit.

Discovery of TP0628103: A Highly Potent and Selective MMP-7 Inhibitor with Reduced OATP-Mediated Clearance Designed by Shifting Isoelectric Points.

Matrix metalloproteinase-7 (MMP-7) has been shown to play an important role in pathophysiological processes such as cancer and fibrosis. We previously discovered selective MMP-7 inhibitors by molecular hybridization and structure-based drug design. However, the systemic clearance (CLtot) of the biologically active lead compound was very high. Because our studies revealed that hepatic uptake by organic anion transporting polypeptide (OATP) was responsible for the high CLtot, we found a novel approach to reducing their uptake based on isoelectric point (IP) values as an indicator for substrate recognition by OATP1B1/1B3. Our "IP shift strategy" to adjust the IP values culminated in the discovery of TP0628103 (18), which is characterized by reduced in vitro OATP-mediated hepatic uptake and in vivo CLtot. Our in vitro-in vivo extrapolation of OATP-mediated clearance and the "IP shift strategy" provide crucial insights for a new medicinal chemistry approach to reducing the systemic clearance of OATP1B1/1B3 substrates.

RAZOR A Lightweight Block Cipher for Security in IoT

Rapid technological developments prompted a need to do everything from anywhere and that is growing due to modern lifestyle. The Internet of Things (IoT) technology is helping to provide the solutions by inter-connecting the smart devices. Lightweight block ciphers are deployed to enable the security in such devices. In this paper, a new lightweight block cipher RAZOR is proposed that is based on a hybrid design technique. The round function of RAZOR is designed by mixing the Feistel and substitution permutation network techniques. The rotation and XOR based diffusion function is applied on 32-bit input with 8 branches and branch number 7 to optimize the security. The strength of RAZOR is proved against differential, linear, and impossible differential attacks. The number of active S-boxes in any 5-round differential characteristic of RAZOR is 21 in comparison to the 10, 6, 4, 7, and 6 for PRESENT, Rectangle, LBlock, GIFT, and SCENERY respectively. RAZOR provides better security than the existing lightweight designs. The average throughput of 1.47 mega bytes per second to encrypt the large files makes it a better choice for software oriented IoT applications.

A Magnet‐Driven Soft Bistable Actuator

AbstractBistable morphing structures are widely used as actuation mechanisms in soft actuators, soft robotics, energy absorbers, mechanical computers, optical lenses, metamaterials, and flexible electronics. However, untethered actuators, repetitive actuators, and hybrid‐assembly (containing in‐plane‐assembly and out‐of‐plane‐assembly) actuators remain challenging to realize using existing bistable structures, which hinders the novel application of such actuators in research, engineering, and daily life. This problem is solved by fabricating a magnet‐driven soft bistable actuator (MSBA) unit. The self‐buckling of the circular polydimethylsiloxane (PDMS) sheet ensures the bistability of the actuator and allows it to operate as an independent unit, free of external constraints. The reorientation of neodymium‐iron‐boron (NdFeB) microparticles embedded in the PDMS sheet enables the dome‐shaped actuators to exhibit repetitive snapping under the stimulus of a direction‐switching magnetic field. The potential of this MSBA unit in bionics, electronics, and biomechanics applications is demonstrated in systematic studies involving modification of the buckling deflection and magnetic moment density. The MSBA unit exhibits excellent performance in hybrid designs and intelligent systems.

High bonding strength of polyphenylene sulfide-aluminum alloy composite structure achieved by constant current anodizing in tartaric acid

The high-strength and facile direct joining of metal to polymer has attracted increasing attention in adhesion. The aluminum alloy (Al) specimen was fabricated by constant current anodization and enlarging treatment. The influences of surface energy, porosity, and anodization time on the interface bonding strength of the injection molding polyphenylene sulfide (PPS)–Al composite structures were quantitatively discussed. Results showed that the bonding strength of the joints was significantly affected by the wettability, porosity, thickness, and pore diameter of the anodized aluminum oxide (AAO) films. When the current density and anodization time were 120 A/m2 and 30 min, the Al surface energy and the bonding strength reached the maximum of 74.8 mN/m and 11.7 MPa. With the enlargement treatment of the AAO film, when the etching duration was 45 min, the bonding strength increased to 25.0 MPa. In general, these results are of great importance to the further design and optimization of the polymer-metal hybrid with reliable interface adhesive strength.

A novel approach for hybrid system simulation and design based on an enhanced load flow calculation methodology

This article presents a modified method of performing power flow calculations as an alternative to pure energy-based simulations of off-grid hybrid systems. The enhancement consists in transforming the scenario-based power flow method into a discrete time dependent algorithm with the inclusion of bus and controller dynamics. The output of the simulation can be then used to run economic calculations as well as for the evaluation of the technical feasibility of a given network configuration.

Performance of 3D printing biomimetic conch shell and pearl shell hybrid design composites under quasi-static three-point bending load

The failure process of biomimetic hybrid design composite composed of layers of conch shell and pearl shell was studied through quasi-static three-point bending experiments and numerical simulations. The biomimetic conch shell structure with inclined angles serves as the upper layer of the hybrid structure, while the biomimetic pearl shell structure with traditional brick and mud structure serves as the lower layer of the hybrid structure, forming a hybrid design structure. Four inclined angles were designed for the structural units of the conch shell, namely 15°, 30°, 45°, and 60°. Twenty-four specimens (six specimens for each inclined angle) were prepared using 3D printing technology using both soft and hard matrix materials. The influence of different inclined angles on the fracture strength, fracture toughness, and energy absorption of hybrid design structures was experimentally studied. The biomimetic hybrid design composite specimen with a notch is placed between two supporting rollers, and a loading indenter acts at mid-span. All twenty-four specimens were notched with a triangular tip and a rectangular bottom. A loading rate of 1 mm/min is used to avoid the viscoelastic effect of the composite materials. Details of the specimens, the experimental set-up and procedure are discussed in this paper. Complementary to the experimental studies, an extensive numerical investigation was carried out to study the influence of the aspect ratio of brick and mud units on the fracture initiation and failure of hybrid design structures. The causes of crack initiation and propagation, and failure modes in biomimetic hybrid design structures were postulated. These numerical findings help in reinforcing the experimental results and provide crucial information to enhance further research in this exciting area.