Search

Summary: We systematically reviewed observational and Mendelian randomization (MR) articles that evaluated the association between obesity and 17 gastrointestinal (GI) diseases to integrate causal and observational evidence. A total of 594 observational studies from 26 systematic reviews and meta‐analyses and nine MR articles were included. For every 5 kg/m2 increase in body mass index (BMI), there was an increased risk of GI diseases ranging from 2% for rectal cancer (relative risk [RR]: 1.02, 95% confidence interval [CI]: 1.01 to 1.03) to 63% for gallbladder disease (RR: 1.63, 95% CI: 1.50 to 1.77). MR articles indicated that risks of developing GI diseases elevated with each 1 standard deviation increase in genetically predicted BMI, ranging from 11% for Crohn's disease to 189% for nonalcoholic fatty liver disease. Moreover, upper GI conditions were less susceptible, whereas hepatobiliary organs were more vulnerable to increased adiposity. Among the associations between obesity and the 17 GI conditions, causal relationships were inferred from only approximately half (10/17, 59%). This study reveals a substantial gap between observational and causal evidence, indicating that a combined approach is necessary to effectively inform public health policies and guide epidemiological research on obesity and GI diseases. [ABSTRACT FROM AUTHOR]

Oxidovanadium meso‐tetrakis(3,4,5‐trimethoxyphenyl) porphyrin [VO(T(OMe)3PP)] (Complex 1) was prepared. The oxidation product of Complex 1 has been characterized by cyclic voltammetry (CV), UV–visible spectrophotometer, electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) by the addition of SbCl5 to Complex 1. There is a one‐electron oxidation product in Complex 1 that creates π–cation radicals in CV data. This is supported by an IR spectrophotometer. Subsequent EPR spectra verified the initiation of the π–cation monoradical, which subsequently transforms into a triplet state where S = 1. DNA binding and antibacterial analysis with Complex 1 have also been analysed. In the DNA‐binding analysis, the CV data confirm the interaction between Complex 1 and DNA. Furthermore, the fact that Complex 1 is more effective at killing bacteria shows that the metal ion's chelation with the porphyrin ligand makes it more lipophilic. [ABSTRACT FROM AUTHOR]

Aurora-A is an essential cell-cycle kinase with critical roles in mitotic entry and spindle dynamics. These functions require binding partners such as CEP192 and TPX2, which modulate both kinase activity and localisation of Aurora-A. Here we investigate the structure and role of the centrosomal Aurora-A:CEP192 complex in the wider molecular network. We find that CEP192 wraps around Aurora-A, occupies the binding sites for mitotic spindle-associated partners, and thus competes with them. Comparison of two different Aurora-A conformations reveals how CEP192 modifies kinase activity through the site used for TPX2-mediated activation. Deleting the Aurora-A-binding interface in CEP192 prevents centrosomal accumulation of Aurora-A, curtails its activation-loop phosphorylation, and reduces spindle-bound TPX2:Aurora-A complexes, resulting in error-prone mitosis. Thus, by supplying the pool of phosphorylated Aurora-A necessary for TPX2 binding, CEP192:Aurora-A complexes regulate spindle function. We propose an evolutionarily conserved spatial hierarchy, which protects genome integrity through fine-tuning and correctly localising Aurora-A activity. Synopsis: The mechanisms underlying the spatiotemporal control of Aurora-A kinase activity during mitosis are not yet determined. This study elucidates both the structure of the human Aurora-A:CEP192 complex and its critical role at the apex of Aurora-A activation in mitosis. CEP192 wraps around the N-lobe of the Aurora-A kinase domain occupying sites that are typically used by the competing microtubule-associated partners TACC3 and TPX2. CEP192 binds the F-pocket/C-helix region of the N-lobe in a way that inhibits Aurora-A, whereas TPX2 binding to the same region activates the kinase. The centrosomal CEP192-Aurora-A complex is the primary driver of Aurora-A auto-phosphorylation during mitosis. Deleting the Aurora-A binding interface of CEP192 causes mitotic spindle defects reminiscent of Aurora-A inhibition. CEP192 facilitates Aurora-A:TPX2 complex formation and activity on the mitotic spindle. The structure of the human Aurora-A:CEP192 complex reveals its importance in facilitating Aurora-A autophosphorylation and activity on the mitotic spindle. [ABSTRACT FROM AUTHOR]

The present study assists the industrial sectors by implementing low‐weight high‐strength aluminium composite. The pristine magnesium as a reinforcement in three different weight percentages (3.5, 7, and 10.5) is utilized to fabricate the A 413 composite using centrifugal casting. The density analysis concludes a higher level of Mg inclusion prompts the material to save 3.9% of weight. Microstructural study of centrifugal casting specimens reveal a rich existence of hard phase Mg2Si in the outer zone, with its richness decreasing toward the inner zone. The tensile test result affirms the functionally graded nature of the material with the increasing trend of tensile strength from the inner to the outer. Fractured surface analysis concludes the existence of cracks and their propagation for the inner region specimen. The influence of magnesium on the surface finish of functionally graded composite at the wire cut electric discharge machining (WEDM) zone is predicted using a machine learning‐based random forest regressor (RFR) algorithm. The supervised learning algorithm declares that 10.5 wt% of Mg facilitates the minimal surface roughness of 0.229 µm with the optimal combination of parameters 6 A of current, 115 µs of pulse‐on time, 60 µs of pulse‐off time, and 8 N of wire tension. [ABSTRACT FROM AUTHOR]

NASICON electrode materials exhibit a broad spectrum of electrochemical potentials, robust ionic conductivity, and structural and thermal stabilities. Using solid state reaction method, Li2Cu2(MoO4)3 was synthesized, a member of NASICON family of compounds based on molybdenum. Various analytical techniques employed to assess structural and morphological properties of synthesized nanomaterial. X‐ray diffraction (XRD) pattern indicated that generated Li2Cu2(MoO4)3 nanomaterial exhibited orthorhombic crystalline structure, with crystallite size of approximately 48 nm. The nanomaterial morphology was evaluated using field emission scanning electron microscopy (FESEM), showing columnar‐ or fiber‐like morphology composed of some conductivity points. The elemental composition of Li2Cu2(MoO4)3 was analyzed by EDAX analysis, confirming the presence of elements lithium, copper, molybdenum, and oxygen. The optical properties and band gap of Li2Cu2(MoO4)3 were analyzed by ultraviolet visible diffuse reflectance spectroscopy (UVDRS). Elemental composition of surface along with electronic states and oxidation states of component present in the nanomaterial Li2Cu2(MoO4)3 were investigated from X‐ray photoelectron spectroscopy (XPS). Electrochemical evaluation using cyclic voltammetry (CV), galvanostatic charge–discharge (GCD), and electrochemical impedance spectroscopic (EIS) showed a specific capacitance of 250 F g−1 at 3.5 A g−1 with the high retention rate of 95.82% after 3000 cycles, indicating its potential for high performance supercapacitors. [ABSTRACT FROM AUTHOR]

Sensor devices, such as accelerometers, are widely used for measuring physical activity (PA). These devices provide outputs at fine granularity (e.g., 10–100 Hz or minute‐level), which while providing rich data on activity patterns, also pose computational challenges with multilevel densely sampled data, resulting in PA records that are measured continuously across multiple days and visits. On the other hand, a scalar health outcome (e.g., BMI) is usually observed only at the individual or visit level. This leads to a discrepancy in numbers of nested levels between the predictors (PA) and outcomes, raising analytic challenges. To address this issue, we proposed a multilevel longitudinal functional principal component analysis (mLFPCA) model to directly model multilevel functional PA inputs in a longitudinal study, and then implemented a longitudinal functional principal component regression (FPCR) to explore the association between PA and obesity‐related health outcomes. Additionally, we conducted a comprehensive simulation study to examine the impact of imbalanced multilevel data on both mLFPCA and FPCR performance and offer guidelines for selecting optimal methods. [ABSTRACT FROM AUTHOR]

Our research aims to design novel pyrimidine derivatives inspired by the common pyrimidine core found in many FDA‐approved drugs. However, extensive prior research on the pyrimidine scaffold has made discovering new molecules more challenging. To overcome this obstacle, we employed a molecular hybridisation strategy, opting to hybridise tetralin and pyrimidine, recognising their potential in cancer therapeutics. The fused pyrimidine was synthesised through a base‐mediated condensation of chalcone with amidine. The reaction conditions were further optimised for base, solvent, temperature and time to produce a series of 21 novel derivatives. These compounds were subsequently screened for anticancer activity against gastric adenocarcinoma cell lines using the MTT assay. Among the synthesised compounds, 2‐(pyridin‐3‐yl)‐4‐(pyridin‐3‐yl)‐5,6‐dihydrobenzo[h]quinazoline 8b and 4‐(2‐(pyridin‐3‐yl)‐5,6 dihydrobenzo[h]quinazolin‐4‐yl) phenol 5g exhibited potent anticancer activity compared to (R)‐Roscovitine. Additionally, a molecular docking study was conducted to assess the reactivity of compound 5g, revealing that the presence of a phenolic hydroxyl group enables hydrogen bonding with CDKs and enhances anticancer activity. Furthermore, the efficacy of compound 5g was validated through an in vitro CDK2/cyclin A2 enzyme inhibition assay. Interestingly, the observed CDK2 inhibitory activity showed a good correlation with the corresponding value for the antiproliferative activity of the tested compounds. [ABSTRACT FROM AUTHOR]

Polymer composites are known for its light weight and specific mechanical characteristics. This study examines sodium hydroxide (NaOH)‐treated coir fiber, an agro‐leftover, stuffed in a polyester matrix with termite frass powder, a bio‐leftover for possible use in light‐weight structural applications. Composite samples were made using compression molding and NaOH‐treated coir fiber reinforced hybrid polymer composite (TCRHPC) with 40 wt% treated coir fiber and 1, 2, 3, and 4 wt% termite frass powder. TCRHPC samples mechanical, water captivation, tribological, and thermal properties were affected by termite frass powder wt%. The TCRHPC sample with 3 wt% termite frass powder has excellent mechanical properties, which improved by tensile (41.6%), flexural (28.57%), impact (43.7%), and hardness (18.84%) properties. With perfect water captivation and low weight increases in normal water (0.017 g), seawater (0.015 g), and NaOH solution (0.010 g), the identical composite sample with thermal stability up to 238°C also reduced wear mass by 5.27%. Conversely, filler agglomeration and heterogeneous dispersion in composite sample impair thermo‐mechanical characteristics of TCRHPC containing 4 wt% termite frass powder. The bonding among polyester, treated coir fiber, and termite frass powder in composites were appraised with the aid of fractographic images of TCRHPC samples. The results show that TCRHPC material suits well for support structures requiring lesser weight. [ABSTRACT FROM AUTHOR]

A pyrene base luminophore was designed and synthesised under ambient conditions using [4+2] annulation. The synthesised probe PYINDP exhibits good optical properties and emits greenish blue, with high colour purity in solid, solution, and thin film phases. In solution, the CIE coordinates were found to be (0.20, 0.48), and for an aggregated state emitting deep green colour, the CIE values are (0.27, 0.65). Room temperature phosphorescence (RTP) is generated by the luminophore PYINDP, owing to the ISC process. Moreover, the emitter demonstrated an excellent limit of detection values in detecting nitroaromatics (NACs). Bio‐imaging studies on HEK, A549 cell lines were successfully carried out to verify the staining capability of PYINDP in biological systems. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is one of the most fatal malignancies in the world. This lethality persists due to lack of effective and efficient treatment strategies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive epithelial malignancy which has a high incidence rate and contributes to overall cancer fatalities. As of 2022, pancreatic cancer contributes to about 3 % of all cancers globally. Over the years, research has characterised germline predisposition, the origin cell, precursor lesions, genetic alterations, structural alterations, transcriptional changes, tumour heterogeneity, metastatic progression, and the tumour microenvironment, which has improved the understanding of PDAC carcinogenesis. By using molecular‐based target therapies, these fundamental advancements support primary prevention, screening, early detection, and treatment. The focus of this review is the use of targeted nanoparticles as an alternative to conventional pancreatic cancer treatment due to the various side effects of the latter. The principles of nanoparticle based cancer therapy is efficient targeting of tumour cells via enhanced permeability and retention (EPR) effects and decrease the chemotherapy side effects due to their non‐specificity. To increase the efficiency of existing therapies and modify target nanoparticles, several molecular markers of pancreatic cancer cells have been identified. Thus pancreatic cancer cells can be detected using appropriately functionalized nanoparticles with specific signalling molecules. Once cancer has been identified, these nanoparticles can kill the tumour by inducing hyperthermia, medication delivery, immunotherapy or gene therapy. As potent co‐delivery methods for adjuvants and tumor‐associated antigens; nanoparticles (NPs) have demonstrated significant promise as delivery vehicles in cancer therapy. This ensures the precise internalization of the functionalized nanoparticle and thus also activates the immune system effectively against tumor cells. This review also discusses the immunological factors behind the uptake of functionalized nanoparticles in cancer therapies. Theranostics, which combine imaging and therapeutic chemicals in a single nanocarrier, are the next generation of medicines. Pancreatic cancer treatment may be revolutionised by the development of a tailored nanocarrier with diagnostic, therapeutic, and imaging capabilities. It is extremely difficult to incorporate various therapeutic modalities into a single nanocarrier without compromising the individual functionalities. Surface modification of nanocarriers with antibodies or proteins will enable to attain multifunctionality which increases the efficiency of pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

Real‐time visualization of metabolic processes in vivo provides crucial insights into conditions like cancer and metabolic disorders. Metabolic magnetic resonance imaging (MRI), by amplifying the signal of pyruvate molecules through hyperpolarization, enables non‐invasive monitoring of metabolic fluxes, aiding in understanding disease progression and treatment response. Signal Amplification By Reversible Exchange (SABRE) presents a simpler, cost‐effective alternative to dissolution dynamic nuclear polarization, eliminating the need for expensive equipment and complex procedures. We present the first in vivo demonstration of metabolic sensing in a human pancreatic cancer xenograft model compared to healthy mice. A novel perfluorinated Iridium SABRE catalyst in a fluorinated solvent and methanol blend facilitated this breakthrough with a 1.2‐fold increase in [1‐13C]pyruvate SABRE hyperpolarization. The perfluorinated moiety allowed easy separation of the heavy‐metal‐containing catalyst from the hyperpolarized [1‐13C]pyruvate target. The perfluorinated catalyst exhibited recyclability, maintaining SABRE‐SHEATH activity through subsequent hyperpolarization cycles with minimal activity loss after the initial two cycles. Remarkably, the catalyst retained activity for at least 10 cycles, with a 3.3‐fold decrease in hyperpolarization potency. This proof‐of‐concept study encourages wider adoption of SABRE hyperpolarized [1‐13C]pyruvate MR for studying in vivo metabolism, aiding in diagnosing stages and monitoring treatment responses in cancer and other diseases. [ABSTRACT FROM AUTHOR]

Introduction: Optimization of ultrafiltration during hemodialysis is a critical parameter in achieving therapeutic efficacy and ensuring hemodynamic stability. While various modalities such as blood volume monitoring, inferior vena cava diameter assessment, natriuretic peptide levels, bioimpedance assay, and lung ultrasound have been widely explored in the context of maintenance hemodialysis, the concept of volume‐guided ultrafiltration in dialysis patients with acute kidney injury remains unexplored. Methods: Adult patients with acute kidney injury requiring dialysis, who were hemodynamically stable and not on ventilator support, without underlying lung pathology or cardiac failure, were randomized into two groups. All patients underwent 28‐zone lung ultrasound before dialysis. The ultrafiltration was decided based on the treating physician's clinical judgment in controls. In the intervention group, the ultrafiltration orders prescribed by the treating physician were modified, based on the Kerley B line scores obtained by lung ultrasound. The rest of the dialysis prescriptions were similar. A postdialysis lung ultrasound was done in both groups to assess the postdialysis volume status 30 min after the dialysis session. Results: A total of 74 patients undergoing hemodialysis for acute kidney injury were randomized. The baseline characteristics were comparable except for higher baseline B line score scores in the intervention arm. All patients received similar dialysis prescriptions. The lung ultrasound‐guided ultrafiltration arm had a higher change in B line scores (BLS) from baseline (4 [0–9.5] vs. 0 [0–4]; p value 0.004) during the first dialysis session. The predialysis BLS indexed to ultrafiltration (mL/kbw/h) were significantly lower in controls, reflecting a relatively higher rate of ultrafiltration in controls compared with intervention (p = 0.006). The total number of dialysis sessions done in the control and intervention arm were 61 and 59, respectively. Among controls, 23/61 sessions (37.7%) had intradialytic adverse events, whereas, in the intervention arm, only 4/59 sessions (6.7) had any adverse intradialytic events (p < 0.01). Conclusion: Lung ultrasound‐guided ultrafiltration was associated with a better safety profile, as demonstrated by reduced intradialytic events. [ABSTRACT FROM AUTHOR]

Five compounds, [Zn2(bpe)(BPTA)2(H2O)2] ⋅ 2H2O (1); [Zn(bpe)(BPTA)] (2); [Cd(bpe)(BPTA)H2O] (3); [Cd(BPTA) (bpmh)] ⋅ 2H2O (4); and Cu2(BPTA)2(bpmh)3(H2O)2] ⋅ 2H2O (5) were prepared employing 2,5‐bis(prop‐2‐yn‐1‐yloxy)terephthalic acid (2, 5 BPTA) as the primary ligand and 1,2‐di(pyridin‐4‐yl)ethane (4, 4′ bpe) (1–3) and 1,2‐bis(pyridin‐3‐ylmethylene)hydrazine (bpmh) (4–5) as the secondary ligands. Single crystal studies indicated that the compounds 1, 3 and 5 have two‐dimensional layer structures and compounds 2 and 4 three‐dimensional structures. The luminescence behaviour of the compounds 2 and 3 were explored for the sensing of metronidazole in aqueous medium. The studies indicated that the compounds can detect metronidazole in ppm level both in solution as well as simple paper strips. The Cu compound 5 was found to lose the coordinated water molecule at 100 °C without any structural change. The coordinatively unsaturated Cu‐centre were examined towards the Lewis acidic character by carrying out the Ullmann type C−C homocoupling reaction of the aromatic halide compounds. The compounds, 4 and 5, also have the Lewis basic functionality arising out the =N−N=, aza groups. The bifunctional nature of the coordination polymers (CP) was explored towards the Chan‐Lam coupling reaction between phenyl boronic acid and aniline derivatives in the ethanol medium. In both the catalytic reactions, good yields and recyclability were observed. The present studies illustrated the rich diversity that the transition metal containing compounds exhibit in extended framework structures. [ABSTRACT FROM AUTHOR]

Borassus flabellifer (Palmyra) fruit fiber (PFF) was extracted and converted into biocarbon materials at different carbonization temperatures of 400°C, 600°C, and 800°C under N2 atmosphere for 1 h. The physicochemical properties of obtained biocarbon materials were investigated via CHNS, SEM‐EDX, FTIR, RAMAN, XRD, BET‐specific surface area, and TGA techniques. The obtained results were correlated with the capacitive energy storage application of biocarbon materials. The highest specific surface area of 46.36 m2 g−1 was observed for the biocarbon materials obtained at 800°C, which also showed superior capacitive performances. The specific capacitances of PFF‐derived biocarbon materials obtained at 400°C, 600°C, and 800°C are respectively found to be 28.58, 37.07, and 45.76 F g−1 at 1 A g−1 employing 1M KOH as electrolyte. The biocarbon materials obtained at 800°C showed the highest specific energy and power of 1.99 and 261 W kg−1 at 1 A g−1. [ABSTRACT FROM AUTHOR]

A major challenge for modern society is securing quality water for various uses. Membrane water treatment will be crucial for drinking water, desalination, and wastewater reuse. The development of bismuth molybdate (Bi2MoO6) nanoparticles has enabled the production of novel Bi2MoO6‐incorporated cellulose acetate (CA) membrane nanocomposite. The synthesized Bi2MoO6/CA nanocomposites are thoroughly examined for their structural, morphological, and photocatalytic characteristics using X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X‐ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) with energy dispersive X‐ray spectroscopy (EDX) analysis. The photocatalytic properties are determined by evaluating the degradation of Malachite Green (MG) and Rose Bengal (RB) by the nanocomposite membranes under the illumination of a UV light simulator. Notably, the Bi2MoO6/CA nanocomposite membrane displays exceptional and sustained photocatalytic efficiency (78%) and (84%) in MG and RB dye degradation, respectively. Moreover, the effective loading of the Bi2MoO6 onto the CA membrane enhances electron and hole adsorption while facilitating carrier movement. Furthermore, the stability exhibited by the Bi2MoO6/CA nanocomposite photocatalysts remains impressive even after multiple cycles, demonstrating their durability. This research introduces a cutting‐edge semiconductor‐based hybrid nanocomposite material that proves highly efficient in the photocatalytic degradation of organic dyes, showcasing promising advancements in environmental remediation strategies. [ABSTRACT FROM AUTHOR]

Background: Cognitive decline is a debilitating symptom in Parkinson's disease (PD). Cognitive impairment in PD has a significant impact on many aspects of an individual's life, social interactions, and overall quality of life (QOL). It is also associated with a faster disease progression and an increased risk of developing dementia. A biopsychosocial approach is likely to address not only the underlying biological mechanisms of cognitive impairment in PD but also the psychological and social factors that can contribute to cognitive decline and influence treatment outcomes. Method: This experimental study was conducted on 60 older adults with PD at Saveetha medical college and hospital. Participants who met the inclusion criteria were randomly allocated into two groups of Biopsychosocial (n = 30) and conventional (n = 30). Participants in the intervention group received the multiple interventions based on the biopsychosocial approach with a duration of 60 min per session. Pre and post‐test evaluation conducted using Scales for Outcomes in PD‐cognition (SCOPA‐cog) and Parkinson disease QOL Questionnaire (PDQ‐8). Result: The results of the study showed that there is a statistically significant difference in the median scores within the Groups for the outcome measures SCOPA‐cog and PDQ‐8 (p < 0.001). For SCOPA‐cog, the BPS group median score increased from 30 to 36, while the Conventional group median score increased from 31 to 33. For PDQ‐8, the BPS group median reduced from 27 to 14, compared to the Conventional group's reduced from 30 to 24. On comparison between the post‐test values, the biopsychosocial approach group showed more improvement in cognition and QOL with (p < 0.001). Conclusion: The findings of this study concluded that the biopsychosocial approach is effective in improving cognition and QOL among the Parkinson population. [ABSTRACT FROM AUTHOR]

Sentiment analysis is an automated approach which is utilized in process of analysing textual data to describe public opinion. The sentiment analysis has major role in creating impact in the day‐to‐day life of individuals. However, a precise interpretation of text still relies as a major concern in classifying sentiment. So, this research introduced Bidirectional Long Short Term Memory with Ranger AdaBelief Optimizer (Bi‐LSTM RAO) to classify sentiment of tweets. Initially, data is obtained from Twitter API, Sentiment 140 and Stanford Sentiment Treebank‐2 (SST‐2). The raw data is pre‐processed and it is subjected to feature extraction which is performed using Bag of Words (BoW) and Term Frequency‐Inverse Document Frequency (TF‐IDF). The feature selection is performed using Gazelle Optimization Algorithm (GOA) which removes the irrelevant or redundant features that maximized model performance and classification is performed using Bi LSTM–RAO. The RAO optimizes the loss function of Bi‐LSTM model that maximized accuracy. The classification accuracy of proposed method for Twitter API, Sentiment 140 and SST 2 dataset is obtained as 909.44%, 99.71% and 99.86%, respectively. These obtained results are comparably higher than ensemble framework, Robustly Optimized BERT and Gated Recurrent Unit (RoBERTa‐GRU), Logistic Regression‐Long Short Term Memory (LR‐LSTM), Convolutional Bi‐LSTM, Sentiment and Context Aware Attention‐based Hybrid Deep Neural Network (SCA‐HDNN) and Stochastic Gradient Descent optimization based Stochastic Gate Neural Network (SGD‐SGNN). [ABSTRACT FROM AUTHOR]

The extensive use of chemical pesticides has significantly boosted agricultural food crop yields. Nevertheless, their excessive and unregulated application has resulted in food contamination and pollution in environmental, aquatic, and agricultural ecosystems. Consequently, the on‐site monitoring of pesticide residues in agricultural practices is paramount to safeguard global food and conservational safety. Traditional pesticide detection methods are cumbersome and ill‐suited for on‐site pesticide finding. The systematic review provides an in‐depth analysis of the current status and perspectives of nanobiosensors (NBS) for pesticide detection in the agricultural arena. Furthermore, the study encompasses the fundamental principles of NBS, the various transduction mechanisms employed, and their incorporation into on‐site detection platforms. Conversely, the assortment of transduction mechanisms, including optical, electrochemical, and piezoelectric tactics, is deliberated in detail, emphasizing its advantages and limitations in pesticide perception. Incorporating NBS into on‐site detection platforms confirms a vital feature of their pertinence. The evaluation reflects the integration of NBS into lab‐on‐a‐chip systems, handheld devices, and wireless sensor networks, permitting real‐time monitoring and data‐driven decision‐making in agronomic settings. The potential for robotics and automation in pesticide detection is also scrutinized, highlighting their role in improving competence and accuracy. Finally, this systematic review provides a complete understanding of the current landscape of NBS for on‐site pesticide sensing. Consequently, we anticipate that this review offers valuable insights that could form the foundation for creating innovative NBS applicable in various fields such as materials science, nanoscience, food technology and environmental science. [ABSTRACT FROM AUTHOR]

We introduce time‐varying extremum graph (tveg), a topological structure to support visualization and analysis of a time‐varying scalar field. The extremum graph is a sub‐structure of the Morse–Smale complex. It captures the adjacency relationship between cells in the Morse decomposition of a scalar field. We define the tveg as a time‐varying extension of the extremum graph and demonstrate how it captures salient feature tracks within a dynamic scalar field. We formulate the construction of the tveg as an optimization problem and describe an algorithm for computing the graph. We also demonstrate the capabilities of tveg towards identification and exploration of topological events such as deletion, generation, split and merge within a dynamic scalar field via comprehensive case studies including a viscous fingers and a 3D von Kármán vortex street dataset. [ABSTRACT FROM AUTHOR]

Tuning the physical and chemical interaction between metal–metal′ (M−M′) and metal–support is an ideal way to realize enhanced catalytic activity of metal nanoparticles (NPs). As a proof of concept, herein we report the fabrication of nickel‐gold (Ni−Au) alloy nanoparticles attached to N‐doped nanoporous carbon (NPC) intervened with MgO (Ni73Au27@MgO‐NPC), achieved through the impregnation of metal precursors into Schiff‐base network polymer (SNP) framework along with Mg(OH)2 and pyrolysis at 800 °C in N2 atmosphere. With high stability and heterogeneity, the nickel rich Ni73Au27@MgO‐NPC exhibited higher catalytic activities with turnover frequencies of 29,272 h−1 (hydrogenation of p‐nitrophenol), 93,843 h−1 (degradation of methyl orange), and 2,218 h−1 (epoxidation of stilbene), compared to commercial 10 wt % Pd/C. Enhanced catalytic activity is correlated to the synchronized electron density enhancement in Au, by Ni and MgO/N‐rich nanoporous carbon heterostructures, as evident from detailed X‐ray photoelectron spectroscopic studies. [ABSTRACT FROM AUTHOR]

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle‐aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age‐related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3‐adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18‐month‐old) C57BL/6JN mice. Sustained β3‐AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a favorable adipokine profile. At the cellular level, CL treatment increased uncoupling protein 1 (UCP1)‐dependent thermogenesis in brown adipose tissue (BAT). However, in white adipose tissue (WAT) depots, CL treatment increased glycerol and lipid de novo lipogenesis (DNL) and turnover suggesting the activation of the futile substrate cycle of lipolysis and reesterification in a UCP1‐independent manner. Increased lipid turnover was also associated with the simultaneous upregulation of proteins involved in glycerol metabolism, fatty acid oxidation, and reesterification in WAT. Further, a dose‐dependent impact of CL treatment on inflammation was observed, particularly in subcutaneous WAT, suggesting a potential mismatch between fatty acid supply and oxidation. These findings indicate that chronic β3‐AR stimulation activates distinct cellular mechanisms that increase energy expenditure in BAT and WAT to improve systemic metabolism in aged mice. Considering that people lose BAT with aging, activation of futile lipid cycling in WAT presents a novel strategy for improving age‐related metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: Benzodiazepine (BDZP) and/or z‐hypnotic dispensing during pregnancy has increased globally, as have rates of autism spectrum disorder (ASD) and attention‐deficit hyperactivity disorder (ADHD). This systematic review and meta‐analysis aimed to estimate the association between gestational exposure to BDZP and/or z‐hypnotics and diagnosis of ASD or ADHD in offspring. Methods: We searched MEDLINE, EMBASE, and SCOPUS from inception till December 2023 for relevant English‐language articles. Outcomes of interest were risk of ASD and ADHD, two independent primary outcomes, in children exposed anytime during pregnancy to BDZP and/or z‐hypnotics versus those unexposed. Secondary outcomes were trimester‐wise analyses. Using a random effects model, we pooled the overall and trimester‐wise hazard ratios (HRs), with 95% confidence intervals (CIs), separately for risk of ASD and ADHD. Results: We found six eligible retrospective cohort studies and no case–control studies. There was no increased risk of ASD associated with anytime gestational BDZP and/or z‐hypnotic exposure (primary outcome, HR, 1.10; 95% CI, 0.81–1.50; 4 studies; n = 3,783,417; 80,270 exposed, 3,703,147 unexposed) nor after first trimester exposure (HR, 1.15; 95% CI, 0.83–1.58; 3 studies; n = 1,539,335; 70,737 exposed, 1,468,598 unexposed) or later trimester exposures. A very small but significantly increased risk of ADHD was noted with anytime gestational exposure to these drugs (primary outcome, HR, 1.07; 95% CI, 1.03–1.12; 4 studies; n = 2,000,777; 78,912 exposed, 1,921,865 unexposed) and also with (only) second trimester exposure (HR, 1.07; 95% CI, 1.03–1.12; 3 studies; n = 1,539,281; 33,355 exposed, 1,505,926 unexposed). Findings were consistent in sensitivity analyses. Conclusion: Gestational exposure to benzodiazepines or z‐hypnotics was not associated with an increased risk of ASD and with only a marginally increased risk of ADHD in offspring. Given the likelihood of confounding by indication and by unmeasured variables in the original studies, our findings should reassure women who need these medications for severe anxiety or insomnia during pregnancy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Bumetanide, a loop diuretic, was identified as a candidate drug for repurposing for Alzheimer's disease (AD) based on its effects on transcriptomic apolipoprotein E signatures. Cross‐sectional analyses of electronic health records suggest that bumetanide is associated with decreased prevalence of AD; however, temporality between bumetanide exposure and AD development has not been established. METHODS: We evaluated Medicare claims data using Cox proportional hazards regression to evaluate the association between time‐dependent use of bumetanide and time to first AD diagnosis while controlling for patient characteristics. Multiple sensitivity analyses were conducted to test the robustness of the findings. RESULTS: We sampled 833,561 Medicare beneficiaries, 60.8% female, with mean (standard deviation) age of 70.4 (12). Bumetanide use was not significantly associated with AD risk (hazard ratio 1.05; 95% confidence interval, 0.99–1.10). DISCUSSION: Using a nationwide dataset and a retrospective cohort study design, we were not able to identify a time‐dependent effect of bumetanide lowering AD risk. Highlights: Bumetanide was identified as a candidate for repurposing for Alzheimer's disease (AD).We evaluated the association between bumetanide use and risk of AD.We used Medicare data and accounted for duration of bumetanide use.Bumetanide use was not significantly associated with risk of AD. [ABSTRACT FROM AUTHOR]

Background: There is ongoing debate around rate versus rhythm control strategies for managing atrial fibrillation (AF), however, much of the data comes from Western cohorts. Kerala‐AF represents the largest prospective AF cohort study from the Indian subcontinent. Objectives: To compare 12‐month outcomes between rate and rhythm control strategies. Methods: Patients aged ≥18 years with non‐transient AF were recruited from 53 hospitals across Kerala. Patients were stratified by rate or rhythm control. The primary outcome was a composite of all‐cause mortality, arterial thromboembolism, acute coronary syndrome or hospitalization due to heart failure or arrhythmia at 12 months. Secondary outcomes included bleeding events and individual components of the primary. Predictors of the composite outcome were analysed by logistic regression. Results: A total of 2901 patients (mean age 64.6 years, 51% female) were included (2464 rate control, 437 rhythm control). Rates of the primary composite outcome did not differ between groups (29.7% vs 30.0%; p =.955), nor did any component of the primary. Bleeding outcomes were also similar (1.6% vs 1.9%; p =.848). Independent predictors of the primary composite outcome were older age (aOR 1.01; p =.013), BMI <18 (aOR 1.51; p =.025), permanent AF (aOR 0.78; p =.010), HFpEF (aOR 1.40; p =.023), HFrEF (aOR 1.39; p =.004), chronic kidney disease (aOR 1.36; p <.001), and prior thromboembolism (aOR 1.31; p =.014). Conclusion: In the Kerala‐AF registry, 12‐month outcomes did not differ between rate and rhythm control cohorts. [ABSTRACT FROM AUTHOR]

The suitable band gap with outstanding optoelectronic characteristics makes Sn‐based perovskites one of the promising candidates for the preparation of efficient lead‐free perovskite solar cells (PSCs). However, preparing Sn2+‐based PSCs is very difficult due to the ready oxidation of Sn2+ to Sn4+ when exposed to air. In this work, by incorporating the trimethylamine borane complex (TMAB) as an antioxidant additive into the perovskite precursor solution along with excess SnF2, we report the fabrication of air‐stable FASnI3‐based solar cells. The complex formed by TMAB‐SNF2 (additive layer) enables in‐situ encapsulation of perovskite grains. This layer considerably improves the oxidation stability of the perovskite layer by eliminating oxygen vacancies from the NiO hole transport. The resulting PSCs can maintain more than 70% of the efficiency over 45 and 75 hours respectively in air and N2 exposure without encapsulation. This can be regarded as a genuinely enhanced attribute, particularly considering the use of carbon in one of the electrodes in FASnI3 perovskites. The findings suggest an alternative approach to provide effective and sustainable Sn‐based PSCs in the future. [ABSTRACT FROM AUTHOR]

In modern times, nanoparticles have materialized as indispensable things in contemporary medicine, with a variety of uses in clinical, drug and gene conveyance. In the present study, TiO2 nanoparticles (NPs) prepared from the leaf extracts of Mollugooppositifolia and Trianthema portulacastrum were compared with the chemical TiO2‐NPs for antibacterial and antioxidant activities and environment‐friendly nature through various tools like the UV‐visible, X‐ray diffraction with the aid of other analytical techniques like HR‐TEM, Fourier transform infrared (FT‐IR) and photoluminescence spectroscopic techniques. The morphology of green TiO2‐NPs is found to be spherical, which is supported by HR‐TEM images. FT‐IR analyses and X‐ray diffraction data ensure that the polycrystalline characters of TiO2‐NPs alike to the presence of metal oxide. TiO2‐NPs showed a possible photocatalytic activity for the ruin of acid black 1 dye after disclosure to sunlight. The chemical and green methods of TiO2‐NPs have acid black 1 dye decomposition rates of 86.66% and 94.33%, respectively. The synthesized TiO2‐NPs are also assessed for antimicrobial and antioxidant activities. Green TiO2‐NPs exhibit antibacterial activity against Pseudomonas aeruginosa (17 + 0.56 mm) and Staphylococcus aureus (16 + 0.24 mm) at concentrations as low as 100 μL. The green TiO2‐NPs showed high inhibition of DPPH I radical (50 μg/m) at 95.17 ± 21. Therefore, TiO2‐NPs represent eco‐friendly properties that aid in the degradation of dyes due to their antioxidant activity. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the potential of hesperetin‐loaded chitosan nanoparticles (HSPCNPs) in alleviating hyperglycemia by modulating key enzymes in diabetic rats. Chitosan nanoparticles loaded with hesperetin were prepared using the ionic gelation method and characterized with Electron microscope (SEM), zeta potential, particle size analysis, Fourier‐transform infrared (FT‐IR), Energy dispersive spectroscopy (EDS) and Encapsulation efficiency and Loading efficiency. To induce diabetes, rats were fed a high‐fat beef tallow diet for 28 days, then given a single dose of streptozotocin (STZ) at 35 mg/kg b.w in 0.1 M citrate buffer (pH 4.0). Rats were treated with HSPCNPs at doses of 10, 20, and 40 mg/kg b.w. The analyzed parameters included body weight, food and water intake, plasma glucose and insulin, liver and skeletal muscle glycogen levels, and carbohydrate metabolism. SEM imaging revealed dimensions between 124.2 and 251.6 nm and a mean particle size of 145.0 nm. FT‐IR analysis confirmed the presence of functional groups in the chitosan nanoparticles, and the zeta potential was 35.5 mV. HSPCNP 40 mg/kg b.w significantly (p < 0.05) reduced blood glucose levels and glycosylated hemoglobin, improving body weight, food intake, and reducing water intake. In diabetic rats, enzymes for carbohydrate metabolism like fructose 1,6‐bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose 6‐phosphatase are evaluated in the liver, while glucose 6 phosphate dehydrogenase and hexokinase activity were significantly lower. Additionally, plasma insulin levels increased, indicating enhanced insulin sensitivity. The results show that HSPCNPs at 40 mg/kg b.w. ameliorate hyperglycemia to provide robust protection against diabetic complications and significantly improve metabolic health. [ABSTRACT FROM AUTHOR]

The scientific community is moving toward a green environment using several nontoxic photon‐absorbing materials like tin, germanium, antimony, and bismuth. Bismuth halides have essential advantages like low toxicity, Earth abundance, good chemical stability, and optoelectronic behavior which make them suitable for lead‐free perovskite solar cells. Herein, a streamlined one‐step spin‐coating technique is employed using DMF to enhance the morphology of thin films based on BiCl3 perovskite. The resulting thin films of methylammonium bismuth halide ((CH3NH3)3Bi2IxCl9−x) display a remarkably uniform, pinhole‐free, and finely nanostructured morphology, ensuring consistent surface coverage. For the development of hole conductor‐free Bi‐perovskite solar cells (PSCs), carbon is utilized as both counter electrode and hole extraction layer. The device configuration entails FTO/Compact TiO2/meso‐TiO2/((CH3NH3)3Bi2IxCl9−x)/Carbon/FTO, a novel arrangement for Bi‐PSCs. Notably, the fabricated devices demonstrate commendable photovoltaic properties, including Voc of 280 mV, Jsc of 0.25 mA, fill factor of 0.60, and a notably elevated power conversion efficiency (PCE) of 0.042% which has proven significantly advantageous in achieving higher PCE. Furthermore, the fabricated devices exhibit robust chemical stability over 40 d when exposed to an ambient atmosphere without encapsulation. The solar cells retain 25% of their initial PCE after 168 h, further highlighting their durability and suitability for practical applications. [ABSTRACT FROM AUTHOR]

Ecological intensification (EI) provides an important and increasingly adopted pathway for achieving more sustainable agricultural systems. However, the implementation and success of on‐farm EI practices may vary depending on landscape context and local management practices.We evaluated how EI interventions, including two different agricultural input regimes (high or low use of synthetic pesticides and fertilizers) and floral border crops, affected local natural enemy biodiversity, pest abundance and crop yield, and how this was influenced by the surrounding landscape context across 12 rice fields on smallholder farms in Puducherry, India.Reducing agricultural inputs positively impacted the overall natural enemy assemblage; however, responses to landscape factors varied. For example, coccinellid beetles were negatively correlated with higher densities of field edges (landscape configuration). In contrast, spiders, the most abundant group surveyed, were not significantly influenced by any landscape metric. Furthermore, pest abundance was greatest in fields with reduced inputs but only at sites where floral border crops were not present.Mean rice grain yield was lower across low‐input sites compared with high‐input sites and floral border crops had opposing effects across high‐ and low‐input sites. At low‐input sites, mean yields were 33% higher where floral border crops were present. At high‐input sites, the presence of floral border crops was correlated with a lower mean yield (16%).These findings show that ecological intensification practices can benefit smallholder crop systems but highlight the need to account for variations in landscape context and local management practices for developing effective sustainable management practices. [ABSTRACT FROM AUTHOR]

This paper investigates the stability and reliability analysis of a non‐isolated high‐gain DC‐DC converter. The proposed DC‐DC converter produces a high gain output voltage with a lower duty ratio and reduced voltage stress on the semiconductor switch. A reliability analysis is performed to predict the failure rate and lifetime of the individual components using the military handbook (MIL‐HDBK‐217F). A state space equation and small signal modeling of the proposed converter are derived to elucidate the performance of the proposed converter through stability analysis. A closed‐loop using PID controller is incorporated to attain the constant regulated output voltage during sudden parameter changes. The validation of the closed‐loop using the PID controller is verified with the wide range of variations in the different parameters, such as input voltage, load value, and reference voltage value. The laboratory‐based prototype is developed for the proposed converter and validated the performance with 250 W. The power density and efficiency of the proposed converter are 1.360 kW/L and 93%, respectively. [ABSTRACT FROM AUTHOR]

Tire industries seek advancements in technologies ranging from novel constructions to new material systems for fuel efficiency. The chemical formulation of tread compounds and their processing conditions can significantly affect tire performance for key attributes, including rolling resistance, wet traction, and wear resistance. Adding demineralized water (DMW) molecules might enhance the silanization reaction between silane and silica filler surface via improved hydrolysis and condensation, resulting in a better silanization reaction. DMW was sprayed on a silica surface before mixing, incorporated with TESPD silane into S‐SBR/BR tire tread compound, and mixed in an internal mixer. The effects of an increase in the DMW content on compound processability, cure characteristics, filler dispersion, dynamic properties, and mechanical properties were investigated. Adding the water‐treated silica into the compound lowered the heat generation during mixing, lowered the dump temperature, lowered the tan δ (E″/E′) at 60°C, and increased the wet grip property by retaining the abrasion resistance compared with the control. The enhancement of filler dispersion was visualized via scanning electron microscope images. Reaction kinetics concerning the addition of water and the effect of the pH of water on the silanization reaction is also discussed using HPLC analysis. [ABSTRACT FROM AUTHOR]

Advances in manufacturing technology coupled with the increased potency of new biotherapeutic modalities have created an external environment where continuous manufacturing (CM) can address a growing need. Amgen has successfully implemented a hybrid CM process for a commercial lifecycle program. In this process, the bioreactor, harvest, capture column, and viral inactivation/depth filtration unit operations were integrated together in an automated, continuous module, while the remaining downstream unit operations took place in stand‐alone batch mode. CM operations are particularly suited for so‐called "high mix, low volume" manufacturing plants, where a variety of molecules are manufactured in relatively low volumes. The selected molecule fit this mold and was manufactured in a low‐capital micro‐footprint suite attached to an existing therapeutic production facility. Use of a hybrid process within an already operating facility required less capital and minimized complexity. To enable this hybrid CM process, an established fed‐batch process was converted to a perfusion process with continuous harvest. Development efforts included both process changes and the generation of a novel cell line adapted to long‐term perfusion. Chromatography resins were updated, and purification processes adapted to handle variable inputs due to the fluctuations in harvest titer from the lengthy production process. A novel automated single‐use (SU) viral inactivation (VI) skid was introduced, which entailed the development of a robust pH verification and alarm system, along with procedures for product isolation to allow discard of specific cycles. The CM process demonstrated consistent performance, meaning it met predefined performance criteria (including product quality attributes, or PQAs) when operated within established process parameters and manufactured according to applicable procedures. Using a 75% reduction in scale, it resulted in a five‐fold reduction in process media and buffer usage, a fifteen‐fold increase in mass per thaw, and an overall process productivity increase of 45‐fold (as measured by grams drug substance per liter per day.) The hybrid CM process also enabled increased material demand to be met with no change in cost of goods manufactured or plant capacity, due to the repurposing of existing facility space and the flexible duration of the hybrid CM harvest. Overall, the success of the hybrid CM platform represents an exciting opportunity to reduce costs and increase process efficiency in industry. [ABSTRACT FROM AUTHOR]

Soybean [Glycine max (L.) Merr] seed is a valuable source of raw materials of protein, oil, and metabolites for food, feed, and pharmaceutical industries. Using global metabolic profiling, we identified 718 non‐redundant metabolites of a fast neutron‐mediated soybean known to have 24 genes deleted and 15% more seed protein compared to wild‐type seed. Among the 554 identified metabolites in leaves and 629 identified in seed, 465 were found in both leaves and seed. Mapping of the deleted genes and identified metabolites indicated a complex perturbation of global metabolism involving glutamine‐arginine, aspartate, aromatic amino acid, glycolytic, and tricarboxylic acid cycle (TCA) pathways. The mutant seed showed a higher content of sulfur‐containing metabolites such as S‐methylmethionine, methionine, and cysteine compared to wild‐type seed. The gene deletions may alter carbon flow from glycolytic and TCA pathways, resulting in higher protein content and increased abundance of sulfur‐containing metabolites in the mutant seeds. The results provide valuable information for altering metabolic pathways to increase value‐added seed traits in soybeans. Core Ideas: Increasing S‐containing amino acids in soybean seeds is needed to improve seed nutritive quality.Untargeted metabolic profiling of a fast neutron soybean mutant was conducted, and global metabolic pathways were analyzed.A possible mechanism of increased content of S‐methylmethionine, methionine, and cysteine was revealed. [ABSTRACT FROM AUTHOR]

The objective of this study is to provide a positron emission tomography (PET) imaging modality targeting vascular endothelial growth factor receptors (VEGFR) for the early noninvasive detection and assessment of pulmonary arterial hypertension (PAH) severity. To validate the effectiveness of the [18F]VEGFR PET tracer, we utilized a monocrotaline (MCT)‐induced PAH rat model. Molecular optical imaging, using a Cy5.5‐conjugated VEGFR targeting agent, was employed to demonstrate the uptake of the agent at pulmonary arterioles, correlating with the onset and progression of PAH. Histological examinations of the MCT‐PAH rat lung revealed a significant correlation between VEGFR2 expression and the pathogenesis of PAH. Molecular optical imaging demonstrated heightened uptake of the Cy5.5‐conjugated VEGFR targeting agent at pulmonary arterioles, corresponding with the onset and progression of PAH. [18F]VEGFR PET showed increased lung uptake detectable in early‐stage PAH before increase in pulmonary artery pressures, and this uptake correlated with increased PAH severity. Moreover, when compared to [18F]FDG PET, [18F]VEGFR PET exhibited markedly lower background cardiac signal, enhancing imaging sensitivity for lung abnormalities. Our study provides a compelling evidence for the potential utility of the innovative [18F]VEGFR PET tracer, in non‐invasively detecting early signs of PAH, and monitoring its progression. The observed correlations between VEGFR2 expression, molecular optical imaging results, and [18F]VEGFR PET findings support the use of this tracer for early detection, and assessment of PAH severity. The lower background cardiac signal observed with [18F]VEGFR PET further enhances its imaging sensitivity, emphasizing its potential clinical significance. [ABSTRACT FROM AUTHOR]

Background and Purpose: α4β2 nicotinic acetylcholine (nACh) receptors assemble in two stoichiometric forms, one of which is potentiated by calcium. The sites of calcium binding that underpin potentiation are not known. Experimental Approach: To identify calcium binding sites, we applied cryo‐electron microscopy (cryo‐EM) and molecular dynamics (MD) simulations to each stoichiometric form of the α4β2 nACh receptor in the presence of calcium ions. To test whether the identified calcium sites are linked to potentiation, we generated mutants of anionic residues at the sites, expressed wild type and mutant receptors in clonal mammalian fibroblasts, and recorded ACh‐elicited single‐channel currents with or without calcium. Key Results: Both cryo‐EM and MD simulations show calcium bound to a site between the extracellular and transmembrane domains of each α4 subunit (ECD‐TMD site). Substituting alanine for anionic residues at the ECD‐TMD site abolishes stoichiometry‐selective calcium potentiation, as monitored by single‐channel patch clamp electrophysiology. Additionally, MD simulation reveals calcium association at subunit interfaces within the extracellular domain. Substituting alanine for anionic residues at the ECD sites reduces or abolishes stoichiometry‐selective calcium potentiation. Conclusions and Implications: Stoichiometry‐selective calcium potentiation of the α4β2 nACh receptor is achieved by calcium association with topographically distinct sites framed by anionic residues within the α4 subunit and between the α4 and β2 subunits. Stoichiometry‐selective calcium potentiation could result from the greater number of calcium sites in the stoichiometric form with three rather than two α4 subunits. The results are relevant to modulation of signalling via α4β2 nACh receptors in physiological and pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Bioactive phytocompounds are crucial components in all plants. Since the time of traditional medicine, the utilization of plants has been grounded in the potential of these bioactive compounds to treat or manage specific illnesses. These natural bioactive compounds have sparked growing interest in employing medicinal plants for addressing various conditions, such as inflammatory diseases, diabetes, and cancer. This study focuses on assessing the qualitative phytochemical composition, antioxidant potential, and cytotoxic effects of blueberry (Vaccinium sect. Cyanococcus) extract using three different solvents, namely water, ethanol, and methanol. The extract exhibited notable antioxidant activities, as evidenced by DPPH and H2O2 free radical scavenging assays. The cell viability assay also demonstrated cell growth inhibition in A549 cells. Furthermore, nine specific phytocompounds sourced from existing literature were selected for molecular docking studies against CDK6 and, AMPK key protein kinases which enhance the cancer progression. The molecular docking results also revealed favorable binding scores, with a high score of −9.5 kcal/mol in CDK6 protein and a maximum score of AMPK with targets of −8.8 kcal/mol. The selected phytocompounds' pharmacodynamic properties such as ADMET also supported the study. Furthermore, rutin stated that pre‐dominantly present in blueberry plants shows a potent cytotoxicity effect in A549 cells. Functional annotations by bioinformatic analysis for rutin also revealed the strong enrichment in the involvement of PI3K/AKT1/STAT, and p53 signaling pathways. Based on this analysis, the identified rutin and other compounds hold a promising anticancer activity. Overall, the comprehensive evaluation of both in vitro and in silico data suggests that the Vaccinium sect. Cyanococcus extract could serve as a valuable source of pharmaceutical agents and may prove effective in future therapeutic applications. Significance statement: This study offers a significant contribution through its comprehensive approach to assess the therapeutic potential of blueberry extract. By integrating biological experiments with bioinformatic functional annotations, the research provides a thorough understanding of the bioactive compounds within blueberries and their potential mechanisms in combating lung cancer progression. Furthermore, the identification of key compounds within the extract, their potent cytotoxic effects on A549 cells and their involvement in crucial signaling pathways associated with lung cancer underscore the promising anticancer properties of blueberry‐derived compounds. This holistic methodology not only validates the traditional use of medicinal plants but also sheds light on their potential as valuable sources of novel pharmaceutical agents for future therapeutic advancements. [ABSTRACT FROM AUTHOR]

The primary aim was to demonstrate bioequivalence between the 10/20 mg fixed‐dose combination (FDC) of macitentan/tadalafil in a single tablet and the free combination of both drugs, and to evaluate the food effect on the 10/20 mg FDC in healthy participants. In this single‐center, randomized, open‐label, 3‐way crossover, single‐dose Phase 1 study in healthy adult participants, macitentan/tadalafil was administered as a 10/20 mg FDC formulation and compared with the free combination of macitentan and tadalafil. The food effect on the FDC was also evaluated. Pharmacokinetic sampling (216 h) was conducted. The 90% confidence intervals (CIs) for the geometric mean ratios of maximum observed plasma analyte concentration (Cmax) and area under the plasma analyte concentration–time curves (AUCs) for Treatment A (FDC, fasted) versus C (free combination, fasted) were within bioequivalence limits demonstrating that the FDC formulation can be considered bioequivalent to the free combination. The 90% CIs for the geometric mean ratios of Cmax and AUC for Treatment B (FDC, fed) versus A (FDC, fasted) were contained within bioequivalence limits demonstrating that there was no food effect. The administration of the 10/20 mg FDC was generally safe and well tolerated in healthy participants. This study demonstrated bioequivalence between the FDC of macitentan/tadalafil (10/20 mg) in a single tablet and the free combination of both drugs in healthy participants, and that the FDC can be taken without regard to food, similarly to the individual components. The FDC was generally safe and well tolerated. [ABSTRACT FROM AUTHOR]

Background: Current hemovigilance methods generally rely on survey data or administrative claims data utilizing billing and revenue codes, each of which has limitations. We used electronic health records (EHR) linked to blood bank data to comprehensively characterize red blood cell (RBC) utilization patterns and trends in three healthcare systems participating in the U.S. Food and Drug Administration Center for Biologics Evaluation and Research Biologics Effectiveness and Safety (BEST) initiative. Methods: We used Information Standard for Blood and Transplant (ISBT) 128 codes linked to EHR from three healthcare systems data sources to identify and quantify RBC‐transfused individuals, RBC transfusion episodes, transfused RBC units, and processing methods per year during 2012–2018. Results: There were 577,822 RBC units transfused among 112,705 patients comprising 345,373 transfusion episodes between 2012 and 2018. Utilization in terms of RBC units and patients increased slightly in one and decreased slightly in the other two healthcare facilities. About 90% of RBC‐transfused patients had 1 (~46%) or 2–5 (~42%)transfusion episodes in 2018. Among the small proportion of patients with ≥12 transfusion episodes per year, approximately 60% of episodes included only one RBC unit. All facilities used leukocyte‐reduced RBCs during the study period whereas irradiated RBC utilization patterns differed across facilities. Discussion: ISBT 128 codes and EHRs were used to observe patterns of RBC transfusion and modification methods at the unit level and patient level in three healthcare systems participating in the BEST initiative. This study shows that the ISBT 128 coding system in an EHR environment provides a feasible source for hemovigilance activities. [ABSTRACT FROM AUTHOR]

Insufficient progress in the development of national highways and state highways, coupled with a lack of public awareness regarding road safety, has resulted in prevalent traffic congestion and a high rate of accidents. Understanding the dominant and contributing factors that may influence road traffic accident severity is essential. This study identified the primary causes and the most significant target‐specific causative factors for road accident severity. A modified partitioning around medoids model determined the dominant road accident features. These clustering algorithms will extract hidden information from the road accident data and generate new features for our implementation. Then, the proposed method is compared with the other state‐of‐the‐art clustering techniques with three performance metrics: the silhouette coefficient, the Davies–Bouldin index, and the Calinski–Harabasz index. This article's main contribution is analyzing six different scenarios (different angles of the problem) concerning grievous and non‐injury accidents. This analysis provides deeper insights into the problem and can assist transport authorities in Tamil Nadu, India, in deriving new rules for road traffic. The output of different scenarios is compared with hierarchical clustering, and the overall clustering of the proposed method is compared with other clustering algorithms. Finally, it is proven that the proposed method outperforms other recently developed techniques. [ABSTRACT FROM AUTHOR]

The sustainable growth of advanced material in metal matrix composites receiving the eco‐friendly hazard‐free composite via recycling waste agro products attains low fabrication cost. The prime goal of this investigation is to develop and strengthen the lightweight aluminum alloy (Al7075) composite through the conservations of 0 wt%, 5 wt%, 10 wt%, and 15 wt% agro‐waste coconut shell using squeeze cast technology. The developed aluminum alloy bio‐composites are promising the best option for replacing conventional metals in several engineering applications like automotive, structural, aerospace, and others. The synthesized Al7075 alloy bio‐composites are studied its physic‐mechanical behavior tag with ASTM standards. The density results revealed nominal improvement, and its mechanical properties of hardness, ultimate tensile strength, and elastic modulus increased significantly. Sample 4 composite contained 15 wt% coconut shell powder found 2.82 ± 0.17 g/cc density with 0.716% porosity level enhanced the hardness, Ultimate tensile strength and elastic modulus of 79 ± 1.1Hv, 238 ± 1.1 MPa and 77.89 ± 2.01 GPa, respectively. [ABSTRACT FROM AUTHOR]

The main objective of the research is developed toward adsorption electronic devices (Interface material) with the performance examined by the physical, mechanical, and thermal properties of the E‐glass fiber reinforced with the epoxy composite and particulate dispersed into the matrix in partial fulfillment of tiny amount of aluminum powder particles and MWCNT. Composite membranes with 15 wt.% E‐glass fiber and 2 wt.%, 4 wt.%, and 6 wt.% fine aluminum powder particle concentrations were partially filled with 0 wt.%, 0.5 wt.%, and 1.0 wt.% MWCNTs. Vacuum lay‐up technique is used to create the better adhesive hybrid composite, which is then assessed of the characteristics of the materials. The maximum thermal conductivity of EAEM2 (E‐Epoxy, A‐Aluminum particle, E‐E‐glass fiber, M‐MWCNT) is 0.3057 W/mK. The tensile, bending, and impact strengths of EAEM1 composites are higher than those of EAEM2 and EAEM3 (average values of EAEM1 composites: 86 MPa, 123.33 MPa, and 90.66 J/m2). However, the Shore‐D hardness of EAEM3 is 95.33. The test findings demonstrate a significant improvement in thermal properties with minimal marginal decrements in mechanical capabilities when carbon allotropes are increased. The composite system's morphology (EAEM3) demonstrates a clustered distribution of aluminum powder particles in the matrix. [ABSTRACT FROM AUTHOR]

The contemporary food industry's uses of nanoemulsions (NEs) include food processing, effective nutraceutical delivery, the development of functional chemicals, and the synthesis of natural preservatives, such as phytocompounds. Although cinnamon essential oil (CEO) is widely used in the cosmetic, pharmaceutical, and food industries, it is difficult to add to aqueous‐based food formulations due to its weak stability and poor water solubility. This study describes the formulation of a CEO nanoemulsion (CEONE) by spontaneous emulsification and evaluates its antibacterial and antibiofilm properties against biofilm‐forming Serratia rubidaea BFMO8 isolated from spoiled emperor fish (Lethrinus miniatus). Bacteria causing spoilage in emperor fish were isolated and identified as S. rubidaea using common morphological, cultural, and 16S RNA sequencing methods, and their ability to form biofilms and their susceptibility to CEONE were assessed using biofilm‐specific methods. The spontaneous emulsification formulation of CEONE was accomplished using water and Tween 20 surfactant by manipulating organic and aqueous phase interface properties and controlling particle growth by capping surfactant increases. The best emulsification, with highly stable nano‐size droplets, was accomplished at 750 rpm and a 1:3 ratio concentration. The stable CEONE droplet size, polydispersity index, and zeta potential values were 204.8 nm, 0.115, and −6.05 mV, respectively. FTIR and high‐resolution liquid chromatography‐mass spectrometry (HR‐LCMS) analyses have revealed carboxyl, carbonyl, and phenol‐like primary phytochemical functional groups in CEO and CEONE, which contribute to their antibacterial and antibiofilm properties. [ABSTRACT FROM AUTHOR]