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Introduction: Sepsis is associated with neurocognitive impairment among preterm neonates but less is known about term neonates with sepsis. This systematic review and meta-analysis aims to provide an update of neurocognitive outcomes including cognitive delay, visual impairment, auditory impairment, and cerebral palsy, among neonates with sepsis., Methods: We performed a systematic review of PubMed, Embase, CENTRAL and Web of Science for eligible studies published between January 2011 and March 2023. We included case-control, cohort studies and cross-sectional studies. Case reports and articles not in English language were excluded. Using the adjusted estimates, we performed random effects model meta-analysis to evaluate the risk of developing neurocognitive impairment among neonates with sepsis., Results: Of 7,909 studies, 24 studies (n = 121,645) were included. Majority of studies were conducted in the United States (n = 7, 29.2%), and all studies were performed among neonates. 17 (70.8%) studies provided follow-up till 30 months. Sepsis was associated with increased risk of cognitive delay [adjusted odds ratio, aOR 1.14 (95% CI: 1.01-1.28)], visual impairment [aOR 2.57 (95%CI: 1.14- 5.82)], hearing impairment [aOR 1.70 (95% CI: 1.02-2.81)] and cerebral palsy [aOR 2.48 (95% CI: 1.03-5.99)]., Conclusion: Neonates surviving sepsis are at a higher risk of poorer neurodevelopment. Current evidence is limited by significant heterogeneity across studies, lack of data related to long-term neurodevelopmental outcomes and term infants., (© 2024. The Author(s).)

In the current situation, peroxynitrite (ONOO - ) is drawing the increasing attention of researchers for its pivotal role in diverse pathological and physiological processes on grounds of robust oxidation and nitrification. Herein, we have successfully designed and synthesized a phenanthrenequinone benzyl borate-based chemosensor for fast and selective detection of ONOO - . The probe PTDP itself had an orange fluorescence, which was changed to strong blue fluorescence upon the addition of ONOO - , indicating the ratiometric response of the probe. This is so because of the cleavage of the benzyl boronate-protecting group of PTDP upon the addition of ONOO - with simultaneous releasing of pyridinyl-based chemosensor PPI . The PTDP showed outstanding performance in the various photophysical studies such as good selectivity, excellent sensitivity with a very low detection limit of 2.74 nM, and a very fast response time (<15 s). Furthermore, for practical applicability, it was successfully applied in the ratiometric detection of ONOO - in osteoblast precursor cells.

Digital PCR (dPCR) has become indispensable in nucleic acid (NA) detection across various fields, including viral diagnostics and mutant detection. However, misclassification of partitions in dPCR can significantly impact accuracy. Despite existing methods to minimize misclassification bias, accurate classification remains elusive, especially for nonamplified target partitions. To address these challenges, this study introduces an innovative microdroplet-based competitive PCR platform for nucleic acid quantification in microfluidic devices independent of Poisson statistics. In this approach, the target concentration (T) is determined from the concentration of competitor DNA (C) at the equivalence point (E.P.), where C/T is 1. Competitive PCR ensures that the ratio of target to competitor DNA remains constant during amplification, reflected in the resultant fluorescence intensity, allowing the quantification of target DNA concentration at the equivalence point. The unique amplification technique eliminates Poisson distribution, addressing misclassification challenges. Additionally, our approach reduces the need for post-PCR procedures and shortens analytical time. We envision this platform as versatile, reproducible, and easily adaptable for driving significant progress in molecular biology and diagnostics.

Objective: The purpose is to evaluate outcomes of alveolar bone grafting based on the pre-grafting orthodontic preparation methods., Design: Retrospective analysis of individuals with unilateral cleft lip and palate., Subjects and Settings: 28 individuals with non-syndromic UCLP from two craniofacial centers, 14 individuals each from XXXX and XXXX., Interventions: The alignment group underwent maxillary expansion with incisors alignment while the non-alignment group underwent only maxillary expansion for presurgical orthodontic preparation., Methods: Initial and post-surgical CBCT scans were compared to observe changes in angulation of the incisor adjacent to the cleft site, alveolar bony root coverage, and bone graft outcomes., Results: In the alignment group, the buccolingual rotation decreased by 32.35 degrees ( p  = .0002), the anteroposterior inclination increased by 14.01 degrees ( p  = .0004), and the mesiodistal angulation decreased by 17.88 degrees ( p  = .0001). Alveolar bony coverage did not change after bone graft in both groups, and no difference was observed between the groups. Chelsea scale showed satisfactory bone graft outcome (category A, C) in 12 cases (85.71%) in the alignment group and 11 cases (78.51%) in the non-alignment group. The volumetric measurement showed the alignment group had better bone fill of 69.85% versus 51.45% in the non-alignment group ( p  = .0495)., Conclusions: Alveolar bony coverage on the tooth adjacent to cleft sites did not change with alveolar bone grafting surgery in either of the alignment and non-alignment group. Presurgical orthodontic alignment does not induce root exposure nor poorer bone grafting outcome., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Numerous efforts have been undertaken to mitigate the Debye screening effect of FET biosensors for achieving higher sensitivity. There are few reports that show sub-femtomolar detection of biomolecules by FET mechanisms but they either suffer from significant background noise or lack robust control. In this aspect, deformed/crumpled graphene has been recently deployed by other researchers for various biomolecule detection like DNA, COVID-19 spike proteins and immunity markers like IL-6 at sub-femtomolar levels. However, the chemical vapor deposition (CVD) approach for graphene fabrication suffers from various surface contamination while the transfer process induces structural defects. In this paper, an alternative fabrication methodology has been proposed where glass substrate has been initially texturized by wet chemical etching through the sacrificial layer of synthesized silver nanoparticles, obtained by annealing of thin silver films leading to solid state dewetting. Graphene has been subsequently deposited by thermal reduction technique from graphene oxide solution. The resulting deformed graphene structure exhibits higher sensor response towards glial fibrillary acidic protein (GFAP) detection with respect to flat graphene owing to the combined effect of reduced Debye screening and higher surface area for receptor immobilization. Additionally, another interesting aspect of the reported work lies in the biomolecule capture by dielectrophoretic (DEP) transport on the crests of the convex surfaces of graphene in a coplanar gated topology structure which has resulted in 10 aM and 28 aM detection limits of GFAP in buffer and undiluted plasma respectively, within 15 min of application of analyte. The detection limit in buffer is almost four decades lower than that documented for GFAP using biosensors which is is expected to pave way for advancing graphene FET based sensors towards ultrasensitive point-of-care diagnosis of GFAP, a biomarker for traumatic brain injury., (© 2024 IOP Publishing Ltd.)

Fog harvesting relies on intercepting atmospheric or industrial fog by placing a porous obstacle, for example, a mesh and collecting the deposited water. In the face of global water scarcity, such fog harvesting has emerged as a viable alternative source of potable water. Typical fog harvesting meshes suffer from poor collection efficiency due to aerodynamic bypassing of the oncoming fog stream and poor collection of the deposited water from the mesh. One pestering challenge in this context is the frequent clogging up of mesh pores by the deposited fog water, which not only yields low drainage efficiency but also generates high aerodynamic resistance to the oncoming fog stream, thereby negatively impacting the fog collection efficiency. Minimizing the clogging is possible by rendering the mesh fibers superhydrophobic, but that entails other detrimental effects like premature dripping and flow-induced re-entrainment of water droplets into the fog stream from the mesh fiber. Herein, we improvise on traditional interweaved metal mesh designs by defining critical parameters, viz., mesh pitch, shade coefficient, and fiber wettability, and deducing their optimal values from numerically and experimentally observed morphology of collected fog water droplets under various operating scenarios. We extend our investigations over a varying range of mesh-wettability, including superhydrophilic and hydrophobic fibers, and go on to find optimal shade coefficients which would theoretically render clog-proof fog harvesting meshes. The aerodynamic, deposition, and overall collection efficiencies are characterized. Hydrophobic meshes with square pores, having fiber diameters smaller than the capillary length scale of water, and an optimal shade coefficient are found to be the most effective design of such clog-proof meshes.

A liquid drop containing a long fiber is a complex system whose configuration is determined by an interplay of elastic stresses in the fiber and capillary forces due to the liquid. We study the morphological evolution of fibers that are much longer than the drop diameter in evaporating sessile drops. After insertion, the fibers are either found in an ordered or disordered state, with increasing disorder for increasing fiber length. Upon evaporation, the order increases, in such a way that the final configuration deposited on the solid surface is either a circle, an ellipse, or 8-shaped. The morphology of the deposit depends on the fiber length and the elastocapillary length, both non-dimensionalized with the characteristic drop size, which we classify in a morphology regime map. The disorder-to-order transition allows depositing ordered fiber structures on solid surfaces even in cases of a strongly disordered state after fiber insertion. Combined with technologies such as inkjet printing, this process could open new avenues to decorate surfaces with filamental structures whose morphology can be controlled by varying the fiber length.

We present an innovative solvent-free micromolding technique for rapidly fabricating complex polymer microparticles with three-dimensional (3D) shapes utilizing a surface tension-induced dipping process. Our fabrication process involves loading a photocurable solution into micromolds through mold dipping. The loaded solution, induced by surface tension, undergoes spatial deformation upon mold removal caused by surface forces, ultimately acquiring an anisotropic shape before photopolymerization. Results show that the amount of photocurable solution loaded depends on the degree of capillary penetration, which can be adjusted by varying the dipping time and mold height. It enables the production of polymer particles with precisely controlled 3D shapes without diluting them with volatile organic solvents. Sequential micromolding enables the spatial stacking of the polymer domain through a bottom-up approach, facilitating the creation of complex multicompartmental microparticles with independently controlled compartments. Finally, we demonstrated the successful simultaneous conjugation of multiple model-fluorescent proteins through the biofunctionalization of microparticles, indicating functional stability and effective conjugation of hydrophilic molecules such as proteins. We also extend our capacity to create bicompartmental microparticles with distinct functionalities in each compartment, revealing spatially controlled functional structures. In summary, these findings demonstrate a straightforward, rapid, and reliable method for producing highly uniform complex particles with precise control over the 3D shape and compartmentalization, all accomplished without the use of organic solvents.

Salicylic acid (SA) finds extensive applications in the treatment of rheumatic and skin diseases because of its analgesic, anti-inflammatory and exfoliating properties. As it is lipophilic in nature, there is a need for appropriate delivery systems to harness these properties for different applications. Herein, we examined the suitability of Pluronic P123/F127 micellar systems as delivery media by investigating the structural, flow and antimicrobial properties of P123/F127-SA solutions and hydrogels using DLS, SANS, rheological and zone inhibition measurement techniques. SA modulates the aggregation characteristics of these surfactant systems and brings about spherical-to-worm-like micelle-to-vesicular structural transitions in the hydrophobic Pluronic P123 system, a spherical-to-worm-like micellar transition in the mixed P123/F127 system and an onset of inter-micellar attraction in the hydrophilic Pluronic F127 system. SA-solubilized systems of both hydrophobic and hydrophilic Pluronics inhibit the growth of Gram-positive and Gram-negative bacteria with comparable MIC values. This suggests that the interaction of SA molecules with the bacterial cell membrane remains unobstructed upon encapsulation in Pluronic micelles. F127 hydrogel-based SA formulations with rheological properties suitable for topical applications and up to 15% SA loading were prepared. These will be useful SA ointments as F127 is an FDA-approved excipient for topical drug delivery applications. The results indicate that Pluronics remain effective as delivery agents for SA and exhibit interesting structural polymorphism upon its solubilization.

Lipid peroxidation (LPO) is a complex process that, depending on the context, can either result in oxidative injury or promote redox homeostasis. LPO is a series of reactions in which polyunsaturated fatty acids are attacked by free radicals that result in the synthesis of lipid peroxides. LPO can alter membrane fluidity and operation and produce secondary products that amplify oxidative stress. LPO can activate cellular signaling pathways that promote antioxidant defense mechanisms that provide oxidative stress protection by elevating antioxidant enzyme action potentials. Enzymatic and nonenzymatic mechanisms tightly regulate LPO to prevent excessive LPO and its adverse consequences. This article emphasizes the dual nature of LPO as a mechanism that can both damage cells and regulate redox homeostasis. In addition, it also highlights the major enzymatic and nonenzymatic mechanisms that tightly regulate LPO to prevent excessive oxidative damage. More importantly, it emphasizes the importance of understanding the cellular and biochemical complexity of LPO for developing strategies targeting this process for efficient management of plant stress., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chetan Keswani reports financial support was provided by Ministry of Science and Higher Education of the Russian Federation., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Improper disposal of waste poses a grave environmental threat, contributing to pollution of air, water, and soil. It is necessary to address this issue in order to mitigate the adverse effects of solid waste on both the environment and public health. In many developing nations, municipal authorities of bigger cities are enduring significant challenges in proper management of waste. The present study evaluates the impacts of various waste management alternative scenarios for environmental impacts for the selected study locations using Life Cycle Assessment (LCA) methodology. The methodology comprised of five different scenarios of waste management including an existing baseline scenario. In this context, the environmental impact categories analyzed were Global Warming potential (GWP), Acidification potential (AP), Eutrophication potential (EP) and Human Toxicity potential (HTP). The results indicated that amongst all the proposed scenarios, Scenario 1 and 4 exhibited the maximum and minimum environmental impacts respectively. The study revealed that least greenhouse gas emissions, acidification potential, eutrophication potential and human toxicity potential were comparatively lesser for scenario 4 varying from 5.65 to 11.36 kg CO 2 eq t -1 ; 1.24-3.345 kg SO 2 eq t -1 , EP 0.19-0.68 kg PO 4 eq t -1 , and 0.35-4.22 kg 1,4-DBeq t -1 respectively. Further, a sensitivity analysis was also performed to evaluate the influence of recycling rate of valuable resources in all the considered scenarios. The sensitivity analysis indicated an inversely proportional relation between change in recycling rate and total environmental burdens., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

As digital pathology replaces conventional glass slide microscopy as a means of reporting cellular pathology samples, the annotation of digital pathology whole slide images is rapidly becoming part of a pathologist's regular practice. Currently, there is no recognizable organization of these annotations, and as a result, pathologists adopt an arbitrary approach to defining regions of interest, leading to irregularity and inconsistency and limiting the downstream efficient use of this valuable effort. In this study, we propose a Standardized Annotation Reporting Style for digital whole slide images. We formed a list of 167 commonly annotated entities (under 12 specialty subcategories) based on review of Royal College of Pathologists and College of American Pathologists documents, feedback from reporting pathologists in our NHS department, and experience in developing annotation dictionaries for PathLAKE research projects. Each entity was assigned a suitable annotation shape, SNOMED CT (SNOMED International) code, and unique color. Additionally, as an example of how the approach could be expanded to specific tumor types, all lung tumors in the fifth World Health Organization of thoracic tumors 2021 were included. The proposed standardization of annotations increases their utility, making them identifiable at low power and searchable across and between cases. This would aid pathologists reporting and reviewing cases and enable annotations to be used for research. This structured approach could serve as the basis for an industry standard and be easily adopted to ensure maximum functionality and efficiency in the use of annotations made during routine clinical examination of digital slides., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Temperature gradient focusing (TGF) relies on establishing a precise balance between the electrophoretic motility of a target analyte and the advective flow of the background electrolyte (BGE) to locally concentrate the analyte in a microfluidic configuration. This paper presents a finite-element-based numerical analysis where the coupled electric field and the transport equations are solved to describe the effects of the shear-dependent apparent viscosity of a non-Newtonian BGE on the localized concentration buildup of a charged bio-sample inside a microchannel by TGF via Joule heating. Effects of the temperature-dependent nature of the wall zeta potential and the flow behavior index (n) of BGE on the flow, thermal, and species concentration profiles inside the microchannel have been investigated. Study using a fluorescein-Na analyte sample shows that the maximum normalized analyte concentration (C max /C 0 ) reduces as the zeta potential increases linearly with temperature. The maximum concentration enhancement is achieved when the BGE displays the Newtonian rheology. For example, C max /C 0 increases 134- to 280-fold when n is increased from 0.8 to 1 (pseudoplastic regime) and again reduces to 190-fold when n increases further from 1 to 1.2 (dilatant regime)., (© 2023 Wiley-VCH GmbH.)

The study reported herein presents the methane generation potential from municipal solid waste (MSW) generated in Kanpur city using four established methods, namely: the IPCC Default Method (DM), EPER Germany, The IPCC First Order Decay (FOD) method, and the Modified Triangular Method (MTM). Results revealed that the average maximum and minimum emissions with respect to total MSW generated and considered over the study period were obtained in the IPCC Default Method (19.17Gg/year) and the MTM (1.00Gg/year), respectively. Furthermore, the sensitivity analysis carried out revealed that the MTM method is the least uncertain method in predicting the methane emissions. Energy generation using the Yedla method and the Stoichiometric method was also carried out, highlighting the potential for energy recovery using methane emissions. The total energy generation potential using the Yedla method over the entire study period was determined to be 924 TJ, with an increased potential of 30% between the periods of 2022 to 2031. According to the study, there exists significant potential for effectively managing the greenhouse gas emissions from open dumpsite by harnessing the methane produced and using it for energy generation., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Obesity and diabetes are associated with elevated free fatty acids like palmitic acid (PA), which promote chronic inflammation and impaired inflammation resolution associated with cardiometabolic disorders. Long noncoding RNAs (lncRNAs) are implicated in inflammatory processes; however, their roles in PA-regulated inflammation and resolution are unclear., Methods: We performed RNA-sequencing analysis to identify PA-regulated coding genes and novel lncRNAs in CD14 + monocytes from healthy volunteers. We investigated the regulation and function of an uncharacterized PA-induced lncRNA PARAIL (PA- r egulated a nti- i nflammatory l ncRNA). We examined its role in inflammation resolution by employing knockdown and overexpression strategies in human and mouse macrophages. We also used RNA pulldown coupled with mass spectrometry to identify PARAIL interacting nuclear proteins and their mechanistic involvement in PARAIL functions in human macrophages., Results: Treatment of human CD14 + monocytes with PA-induced several lncRNAs and genes associated with inflammatory phenotype. PA strongly induced lncRNA PARAIL expressed near RIPK2 . PARAIL was also induced by cytokines and infectious agents in human monocytes/macrophages and was regulated by NF-κB (nuclear factor-kappa B). Time course studies showed PARAIL was induced during inflammation resolution phase in PA-treated macrophages. PARAIL knockdown with antisense oligonucleotides upregulated key inflammatory genes and vice versa with PARAIL overexpression. We found that PARAIL interacts with ELAVL1 (ELAV-like RNA-binding protein 1) protein via adenylate/uridylate-rich elements (AU-rich elements; AREs). ELAVL1 knockdown inhibited the anti-inflammatory functions of PARAIL . Moreover, PARAIL knockdown increased cytosolic localization of ELAVL1 and increased the stability of ARE-containing inflammatory genes. Mouse orthologous Parail was downregulated in macrophages from mice with diabetes and atherosclerosis. Parail overexpression attenuated proinflammatory genes in mouse macrophages., Conclusions: Upregulation of PARAIL under acute inflammatory conditions contributes to proresolution mechanisms via PARAIL -ELAVL1 interactions. Conversely, PARAIL downregulation in cardiometabolic diseases enhances ELAVL1 function and impairs inflammation resolution to further augment inflammation. Thus, inflammation-resolving lncRNAs like PARAIL represent novel targets to combat inflammatory cardiometabolic diseases., Competing Interests: Disclosures None.

Tuning surface properties of nanoparticles by introducing charge, surface functionalization, or polymer grafting is central to their stability and applications. Here, we show that introducing non-DLVO forces like steric and hydrophobic effects in charged silica nanoparticle suspensions through interaction with a nonionic surfactant brings about interesting modulations in their interparticle interaction and phase behavior. The Ludox TM-40 negatively charged silica suspensions thus exhibit liquid-liquid phase separation driven by the onset of interparticle attraction in the system in the presence of the triblock copolymer Pluronic P123. The observed phase separations are thermoresponsive in nature, as they are associated with lower consolute temperatures and a re-entrant behavior as a function of temperature. The nanoparticle-Pluronic system thus undergoes transformation from one-phase to two-phase and then back to one-phase with monotonic increase in temperature. Evolution of the interparticle interaction in the composite system is investigated by dynamic light scattering (DLS), small angle neutron scattering (SANS), zeta potential, rheological, and fluorescence spectroscopy studies. Zeta potential studies show that the charge interaction in the system is partially mitigated through adsorption of a Pluronic micellar layer on the nanoparticle surfaces. Contrast-matching SANS studies suggest that hydrophobic interactions between the adsorbed micellar layer bring about the onset of interparticle attraction in the system. The results are unique and not reported hitherto in charged silica nanoparticle systems.

For various industrial processes, the stabilization of an oil phase is crucial and demands a proper balance of complex interactions in an emulsion system. In Pickering emulsions, this is achieved by introducing nanoparticles, which become organized at the oil-water interface. The influence of interparticle interactions towards the formation of a stable emulsion and the ordering of the stabilizing nanoparticles is intriguing and needs attention. In this work, the role of amphiphilic interactions between hydrophilic silica nanoparticles and the Pluronic F127 tri-block co-polymer towards the spontaneous formation of a fairly stable Pickering emulsion has been studied using small-angle X-ray scattering. Unlike the usual random arrangements of the nanoparticles in a conventional Pickering emulsion, we observed highly organized silica nanoparticles at the oil-water interface. The established standard raspberry structural model of the Pickering emulsion fails to explain such strong ordering as observed in the present case. A plausible formation mechanism of the present Pickering emulsion with a high on-surface silica correlation is elucidated on the basis of the combined interactions of the block co-polymer and silica particles. A computer model is developed to elucidate the effects of size and distribution of the surface-decorating nanoparticles and their positional correlation.

Recently in the field of chemotherapeutics, to combat the side effects of cisplatin, ruthenium complexes have been investigated extensively. In this work, a bidentate benzimidazole-based ligand, HL [HL = 2-(1 H -benzo[ d ]imidazol-2-yl)-6-methoxyphenol], was utilized to obtain three Ru(II) arene complexes having a generalized formula [Ru(η 6 - p -cym)(L)(X)] or [Ru(η 6 - p -cym)(L)(X)] + (where p -cym = p -cymene). The co-ligand X (X = (i) Cl, (ii) PPh 3 = triphenyl phosphine, and (iii) PTA = 1,3,5-triaza-7-phosphaadamantane) was varied in order to study the effect it has on the antitumor activity of the compounds. The synthesized compounds were thoroughly characterized using different analytical techniques, including ESI-MS, NMR, FTIR, UV-Vis, and fluorescence spectroscopy. A fluorescence quenching experiment with serum albumin proteins revealed good interactions between the complexes and HSA and BSA. An analysis of their lipophilic character via the shake flask method and a stability study using UV spectroscopy were conducted as well. The anticancer properties of the synthesized compounds were further explored by conducting a DNA binding study using absorption spectroscopy and fluorometric titration with DAPI to check the mode of binding with DNA. Interestingly, the complexes were also found to catalyze the oxidation of NADH to NAD + , giving rise to radical species in the cells. An immunoblot analysis strongly suggested that all three complexes can remarkably upregulate the expression of cleaved caspase-3 and downregulate the expression of the anti-apoptotic protein BCL XL . It is important to note that such studies are yet to be reported for similar benzimidazole-based ruthenium complexes and therefore present a new direction for the investigation of antitumor ruthenium-based metallodrugs. Furthermore, Hoechst and AO/EtBr staining was used to analyze the morphological changes of the compound-treated cancer cells due to apoptosis, which was also confirmed by the IC 50 values obtained from the colorimetric assay (MTT) against different cancer cell lines.

The buildup of lipids, cholesterol, and other substances in and on the walls of the arteries is known as atherosclerosis and deposition is known as atherosclerotic plaque. Urokinase-type plasminogen activator (uPA) has multiple roles in the atherosclerotic plaque formation and even work simultaneously in making the atherosclerotic plaque unstable. Extracellular matrix plays a major role in the plaque remodeling and rapture. In this study, we have accessed that a higher interaction was observed in the molecular interaction score for uPA with ZINC380065722 having a GOLD fitness score of about 67.60, which is much higher as compared to the known standard inhibitor UK 122 which has reported an interaction score of 59.14. Ser217 and Asp192 are found to be the key amino acid residues in almost all the interactions. Protein frustration analysis has shown that these amino acid residues play a crucial role in the retention of the active pocket conformation and any mutation of these two residues can causes serious decrease in the overall function of the protein. It was observed that the molecule ZINC380065722 remained bound to the protein till 100   ns of simulation time. The average SASA for the apo-uPA and uPA-ligand complex was found to be stable. The network of hydrogen bonds for the intramolecular protein secondary structure and with the solvent system for the apo-protein and the uPA-ligand complex was found to be consistent.Communicated by Ramaswamy H. Sarma.

Condensing atmospheric water vapor on surfaces is a sustainable approach to addressing the potable water crisis. However, despite extensive research, a key question remains: what is the optimal combination of the mode and mechanism of condensation as well as the surface wettability for the best possible water harvesting efficacy? Here, we show how various modes of condensation fare differently in a humid air environment. During condensation from humid air, it is important to note that the thermal resistance across the condensate is nondominant, and the energy transfer is controlled by vapor diffusion across the boundary layer and condensate drainage from the condenser surface. This implies that, unlike condensation from pure steam, filmwise condensation from humid air would exhibit the highest water collection efficiency on superhydrophilic surfaces. To demonstrate this, we measured the condensation rates on different sets of superhydrophilic and superhydrophobic surfaces that were cooled below the dew points using a Peltier cooler. Experiments were performed over a wide range of degrees of subcooling (10-26 °C) and humidity-ratio differences (5-45 g/kg of dry air). Depending upon the thermodynamic parameters, the condensation rate is found to be 57-333% higher on the superhydrophilic surfaces compared to the superhydrophobic ones. The findings of the study dispel ambiguity about the preferred mode of vapor condensation from humid air on wettability-engineered surfaces and lead to the design of efficient atmospheric water harvesting systems.

The world due to increased urbanization and globalization is facing major environmental challenges. Anthropogenic emissions of Greenhouse gases (GHG) like carbon dioxide and methane are on the rise and unsustainable which needs to be regulated. Open dumping of Municipal Solid Waste (MSW) contributes to generation of greenhouse gases like carbon dioxide and methane. This is because large fractions of the waste open dumped are organic in nature which undergoes anaerobic decomposition leading to generation of GHGs. In particular, methane has a high potential for energy generation and if utilized could be highly beneficial. The present study assesses the generation of landfill gases, primarily methane generation potential from MSW generated in Kanpur city using LandGEM 3.02 version model developed by USEPA for the period 2015-2030. It was observed from the study that the cumulative LFGs generation, methane emission and energy recovery potential estimated as 233.44 × 10 6  m 3 , 116 × 10 6  m 3 and 858.14 × 10 6 MJ respectively. Uncertainty analysis carried out showed that variation in methane emissions maybe attributed to input parameters of k and L o of the LandGEM model. The study shows that there exists high potential to control the greenhouse gas emissions by utilizing the methane generated for energy production., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Diabetes mellitus (DM) is one of the most common metabolic disorders characterized by elevated blood glucose levels. Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy, nephropathy, retinopathy, cardiovascular disorders, and diabetic foot ulcers. Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications. Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase, heme oxygenase-1, superoxide dismutase, and catalase that are essential in maintaining redox balance, and ameliorate oxidative stress. Caffeic acid (CA) is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties includ-ing antioxidant, anti-inflammatory, anti-atherosclerotic, immune-stimulatory, cardioprotective, antiproliferative, and hepatoprotective activities. CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets. These include various transcription factors such as nuclear factor-B, tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and nuclear factor erythroid 2-related factor 2. Therefore, this review summarizes the pharmacological properties, molecular mechanisms, and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications. The bioavailability, drug delivery, and clinical trials of CA have also been discussed., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Malaria remains one of the most virulent and deadliest parasitic disease in the world, particularly in Africa and Southeast Asia. Widespread occurrence of artemisinin-resistant Plasmodium falciparum strains from the Greater Mekong Subregion is alarming. This hinders the national economies, as well as being a major drawback in the effective control and elimination of malaria worldwide. Clearly, an effective anti-malarial drug is urgently needed., Methods: The dinuclear and mononuclear copper(II) and zinc(II) complexes were synthesized in ethanolic solution and characterized by various physical measurements (FTIR, CHN elemental analysis, solubility, ESI-MS, UV-Visible, conductivity and magnetic moment, and NMR). X-ray crystal structure of the dicopper(II) complex was determined. The in vitro haemolytic activities of these metal complexes were evaluated spectroscopically on B+ blood while the anti-malarial potency was performed in vitro on blood stage drug-sensitive Plasmodium falciparum 3D7 (Pf3D7) and artemisinin-resistant Plasmodium falciparum IPC5202 (Pf5202) with fluorescence dye. Mode of action of metal complexes were conducted to determine the formation of reactive oxygen species using PNDA and DCFH-DA dyes, JC-1 depolarization of mitochondrial membrane potential, malarial 20S proteasome inhibition with parasite lysate, and morphological studies using Giemsa and Hoechst stains., Results: Copper(II) complexes showed anti-malarial potency against both Pf3D7 and Pf5202 in sub-micromolar to micromolar range. The zinc(II) complexes were effective against Pf3D7 with excellent therapeutic index but encountered total resistance against Pf5202. Among the four, the dinuclear copper(II) complex was the most potent against both strains. The zinc(II) complexes caused no haemolysis of RBC while copper(II) complexes induced increased haemolysis with increasing concentration. Further mechanistic studies of both copper(II) complexes on both Pf3D7 and Pf5202 strains showed induction of ROS, 20S malarial proteasome inhibition, loss of mitochondrial membrane potential and morphological features indicative of apoptosis., Conclusion: The dinuclear [Cu(phen)-4,4'-bipy-Cu(phen)](NO 3 ) 4 is highly potent and can overcome the total drug-resistance of Pf5202 towards chloroquine and artemisinin. The other three copper(II) and zinc(II) complexes were only effective towards the drug-sensitive Pf3D7, with the latter causing no haemolysis of RBC. Their mode of action involves multiple targets., (© 2022. The Author(s).)

Effective manipulation of liquids on open surfaces without external energy input is indispensable for the advancement of point-of-care diagnostic devices. Open-surface microfluidics has the potential to benefit health care, especially in the developing world. This review highlights the prospects for harnessing capillary forces on surface-microfluidic platforms, chiefly by inducing smooth gradients or sharp steps of wettability on substrates, to elicit passive liquid transport and higher-order fluidic manipulations without off-the-chip energy sources. A broad spectrum of the recent progress in the emerging field of passive surface microfluidics is highlighted, and its promise for developing facile, low-cost, easy-to-operate microfluidic devices is discussed in light of recent applications, not only in the domain of biomedical microfluidics but also in the general areas of energy and water conservation.

Rad6, an E2 ubiquitin-conjugating enzyme conserved from yeast to humans, functions in transcription, genome maintenance, and proteostasis. The contributions of many conserved secondary structures of Rad6 and its human homologs UBE2A and UBE2B to their biological functions are not understood. A mutant RAD6 allele with a missense substitution at alanine-126 (A126) of helix-3 that causes defects in telomeric gene silencing, DNA repair, and protein degradation was reported over 2 decades ago. Here, using a combination of genetics, biochemical, biophysical, and computational approaches, we discovered that helix-3 A126 mutations compromise the ability of Rad6 to ubiquitinate target proteins without disrupting interactions with partner E3 ubiquitin-ligases that are required for their various biological functions in vivo. Explaining the defective in vitro or in vivo ubiquitination activities, molecular dynamics simulations and NMR showed that helix-3 A126 mutations cause local disorder of the catalytic pocket of Rad6 in addition to disorganizing the global structure of the protein to decrease its stability in vivo. We also show that helix-3 A126 mutations deform the structures of UBE2A and UBE2B, the human Rad6 homologs, and compromise the in vitro ubiquitination activity and folding of UBE2B. Providing insights into their ubiquitination defects, we determined helix-3 A126 mutations impair the initial ubiquitin charging and the final discharging steps during substrate ubiquitination by Rad6. In summary, our studies reveal that the conserved helix-3 is a crucial structural constituent that controls the organization of catalytic pockets, enzymatic activities, and biological functions of the Rad6-family E2 ubiquitin-conjugating enzymes., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Correct and effective performance evaluation of wastewater treatment plants is a tough task because of the complex biological, physico-chemical, and biochemical processes and associated variables affecting their performance. Conventionally, the efficiency of sewage treatment plants (STPs) are obtained using some index relating pollutant removal efficiency with energy used or costs. These indicators consider only one variable at a time. This leads to incorrect assessment of efficiency, which in turn could adversely affect decision-making of the regulatory authorities. The data envelope analysis (DEA) method utilizes a Linear programming technique which can handle multiple input/output variables without requiring the cost function. This makes it an appropriate tool for assessing the relative efficiency of treatment plants. The present study assess the efficiency of 30 STPs in Delhi, India, using the tolerance-based DEA model utilizing the variable return of scale (VRS). The uncertainty was incorporated into the model using the tolerance measure. The model is solved using the "Add on" option in spreadsheet toolbox of excel solver. Results reveal that out of the 30 plants considered for the study, 6 are performing well (20%). Further, it was observed that a slight change in the input data leads to instability of the efficiency results. Lastly, the ranking is used to determine the treatment plant with best efficiency under all scenarios for the larger period of the year. Such studies will help in chalking out the best management practices that could be adopted by other regulatory authorities., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Visible-light driven photoreactions using transition metal complexes as catalysts are currently a research hotspot in developing environmentally friendly sustainable processes. To develop a potential copper-based photocatalyst, a binuclear Cu(II) complex has been synthesized using a Mannich base ligand viz . 2,4-dichloro-6-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)phenol ( H 2 L ). The photocatalyst has been characterized using ESI-MS and single crystal X-ray diffraction. Under the irradiation of visible light, the catalyst can catalyze hydrogen auto-transfer in N -alkylated amine formation and benzyl alcohol oxidation reactions with excellent conversion. A plausible mechanistic pathway for catalytic reactions has been explored through ESI-MS spectrometric, UV-Vis spectroscopic and computational studies.

Introduction: Clinicians are baffling for reconstruction of small- to medium-sized defects of the oral cavity since time immemorial, each and every flap has its own limitations, ideal flap should be pliable, easily transferrable that can result in a better restoration of form and function of oral mucosa, we have platysma for the same purpose., Aims: We aim to provide surgical technique of the superiorly-based platysma myocutaneous flap with a single neck incision in this study, as well as the flap design, results, and complications associated with age, gender, the recipient site, and the size of the defect., Materials and Methods: Study included 20 patients with oral potentially malignant disorders operated under local anaesthesia with wide local excision and reconstruction with platysma myocutaneous flap at a single tertiary care centre ., Statistical Analysis: The association between the variables was calculated using Chi-square tests and paired t tests. P  <  . 05 was considered significant., Results: Five cases of dehiscence were found at varied sites and flap viability was significantly influenced by location of skin paddle. In between anterior jugular vein and posterior external jugular vein it was 100% viable while on and posterior to the vein, had skin paddle loss. Significant improvement in mouth opening was also seen in Oral Sub-mucous Fibrosis patients., Conclusion: The platysma flap is a technique sensitive, and its results are promising for the reconstruction of oral defects., (© The Association of Oral and Maxillofacial Surgeons of India 2021.)

Objective: This systematic review aimed to summarize the morphologic changes in the temporomandibular joint (TMJ) in patients who underwent orthodontic treatment and were assessed by 3-dimensional (3D) imaging techniques (e.g., magnetic resonance imaging, cone beam computed tomography, and multidetector computed tomography)., Study Design: The authors searched PubMed, Web of Science, and Embase databases to identify original articles from 2014 to 2021 containing keywords for morphologic changes in the TMJ, orthodontic treatment, and three-dimensional imaging methods. Prospective and retrospective studies, including observational, cross-sectional, randomized, and nonrandomized clinical trials, cohort studies, and case-control studies, were reviewed. The review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The risk of bias was assessed in studies selected for the full-text review., Results: The search strategy yielded 294 publications. After an initial screening and the application of exclusion criteria, 13 studies were selected for the final review., Conclusion: Differences were found in condylar positioning, typically in an anterior position; condylar morphology, primarily with increased diameter or head height; and articular disk position within the anterior-posterior plane post-treatment. Changes in the glenoid fossa were not consistent between the studies. The overall risk of bias among studies was moderate. The influence of orthodontic treatment on morphologic changes in the TMJ remains unclear., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Magnetic nanoparticles as drug carriers, despite showing immense promises in preclinical trials, have remained to be only of limited use in real therapeutic practice primarily due to unresolved anomalies concerning their grossly contrasting controllability and variability in performance in artificial test benches as compared to human tissues. To circumvent the deficits of reported in vitro drug testing platforms that deviate significantly from the physiological features of the living systems and result in this puzzling contrast, here, we fabricate a biomimetic microvasculature in a flexible tissue phantom and demonstrate distinctive mechanisms of magnetic-field-assisted controllable penetration of biocompatible iron oxide nanoparticles across the same, exclusively modulated by tissue deformability, which has by far remained unraveled. Our experiments deciphering the transport of magnetic nanoparticles in a blood analogue medium unveil a decisive interplay of the flexibility of the microvascular pathways, magnetic pull, and viscous friction toward orchestrating the optimal vascular penetration and targeting efficacy of the nanoparticles in colorectal tissue-mimicking bioengineered media. Subsequent studies with biological cells confirm the viability of using localized magnetic forces for aiding nanoparticle penetration within cancerous lesions. We establish nontrivially favorable conditions to induce a threshold force for vascular rupture and eventual target of the nanoparticles toward the desired extracellular site. These findings appear to be critical in converging the success of in vitro trials toward patient-specific targeted therapies depending on personalized vascular properties obtained from medical imaging data.

Baicalin is a natural bioactive compound derived from Scutellaria baicalensis , which is extensively used in traditional Chinese medicine. A literature survey demonstrated the broad spectrum of health benefits of baicalin such as antioxidant, anticancer, anti-inflammatory, antimicrobial, cardio-protective, hepatoprotective, renal protective, and neuroprotective properties. Baicalin is hydrolyzed to its metabolite baicalein by the action of gut microbiota, which is further reconverted to baicalin via phase 2 metabolism in the liver. Many studies have suggested that baicalin exhibits therapeutic potential against several types of hepatic disorders including hepatic fibrosis, xenobiotic-induced liver injury, fatty liver disease, viral hepatitis, cholestasis, ulcerative colitis, hepatocellular and colorectal cancer. During in vitro and in vivo examinations, it has been observed that baicalin showed a protective role against liver and gut-associated abnormalities by modifying several signaling pathways such as nuclear factor-kappa B, transforming growth factor beta 1/SMAD3, sirtuin 1, p38/mitogen-activated protein kinase/Janus kinase, and calcium/calmodulin-dependent protein kinase kinaseβ/adenosine monophosphate-activated protein kinase/acetyl-coenzyme A carboxylase pathways. Furthermore, baicalin also regulates the expression of fibrotic genes such as smooth muscle actin, connective tissue growth factor, β-catenin, and inflammatory cytokines such as interferon gamma, interleukin-6 (IL-6), tumor necrosis factor-alpha, and IL-1β, and attenuates the production of apoptotic proteins such as caspase-3, caspase-9 and B-cell lymphoma 2. However, due to its low solubility and poor bioavailability, widespread therapeutic applications of baicalin still remain a challenge. This review summarized the hepatic and gastrointestinal protective attributes of baicalin with an emphasis on the molecular mechanisms that regulate the interaction of baicalin with the gut microbiota., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: This systematic review aims for the explanation of possible postoperative complications, efficacy and limitations of Platysma myocutaneous flap (PMF) in patients with oral submucosal fibrosis (OSMF)., Method: An electronic search of the literature was undertaken using PubMed, Cochrane Library, clinical trials.gov in the year 2021, using MeSH terms and keywords to identify prospective, retrospective and observational studies, controlled trials as well as case reports over the period 1913 to December 2021, addressing the patients with a mouth opening <25 mm and habit of gutkha chewing. PMFs are used as a form of intervention. Patient follow up period should be mentioned., Results: A total of 5 publications were included. 2 were prospective studies and 3 were case reports with 79 subjects between the ages of 18 and 45. All included studies reported complications in a non-significant way (p-value = 0.870) with positive results as they impact the patient's functional outcome (mouth opening) in a statistically significant manner (p < 0.0001 and 95% CI) with good patient compliance., Conclusion: PMF is rarely used in routine practice due to their technical difficulty and potential complications like venous congestion and necrosis. In this systematic review, the authors provide valuable insight into the causes of complications and the efficacy of PMFs in OSMF patients. In the process of platysma flap harvesting, it is especially important to preserve the skin flap, arterial perforators and arteries, veins in supra and sub-platysmal flap elevation. Aside from proper flap placement and tunnelling, postoperative care is equally important., Competing Interests: The authors declare that they have no competing interests., (© 2022 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

Water is the most important commodity available on earth and exists as both surface and sub-surface sources, but increased water pollution has reduced its potability. In this context, it has become imperative to regularly monitor the water quality. In situ and laboratory experimental procedures involve point wise collection of samples for quality determination which are too elaborative and time consuming. As such, the use of methods like Geographic Information System (GIS) modelling if used in collaboration with the traditional methods can prove to be a great tool as they are less expensive and gives a complete spatial resolution of the study site. Therefore, the present study focuses on the determination of water quality using traditional methods in collaboration with GIS modelling system using the inverse distance weighing (IDW) method for two natural lakes in Haryana. The IDW technique was used to interpolate parameters like temperature, dissolved oxygen (DO), nitrates (NO 3 ) and total phosphorous (TP) as they represent the effects of recent and old pollution in lake waters at different depths. These parameters were interpolated for determining the overall water quality status for the lakes. The collaboration can prove to be of great practical significance in today's time by giving an elaborative view of the present water quality status, easing daily telemetric monitoring of the sites as well as give an opportunity for futuristic modelling. The technique can work for almost all the sites around the globe which have either not been evaluated from quality aspect or are inaccessible for monitoring. Parameters like temperature and DO show significant depth wise and seasonal variations for both the lakes with highest values observed at the surface levels, whereas the NO 3 and TP represented effects of point pollution sources to a smaller extent. The maximum value of temperature was determined to be of 30.7 °C and 9 mg/l for DO and was recorded at the surface of lakes 2 and 1, respectively. Further, nitrate and phosphorous concentrations were observed to have maximum values of 0.99 and 0.5 mg/l at the centre of the lake 1 for monsoon season due to influx of pollutants and settlements in the bed. The primary reason for the variation of water quality may be attributed to increased sedimentation at the bottom of lake due to agricultural activities in the vicinity which creates impacts on different hydrodynamic processes leading to increased levels of TP and NO 3 concentrations. Further, increased recreational activities lead to induced variations in the water quality as well., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Inorganic macrocycles remain challenging synthetic targets due to the limited number of strategies reported for their syntheses. Among these species, large fully inorganic cyclodiphosphazane macrocycles have been experimentally and theoretically highlighted as promising candidates for supramolecular chemistry. In contrast, their hybrid organic-inorganic counterparts are lagging behind due to the lack of synthetic routes capable of controlling the size and topological arrangement (i.e., folded vs unfolded) of the target macrocycle, rendering the synthesis of differently sized macrocycles a tedious screening process. Herein, we report-as a proof-of-concept-the combination of pre-arranged building blocks and a two-step synthetic route to rationally enable access a large unfolded tetrameric macrocycle, which is not accessible via conventional synthetic strategies. The obtained macrocycle hybrid cyclodiphosphazane macrocycle, cis-[μ-P(μ-N t Bu)] 2 (μ-p-OC 6 H 4 C(O)O)] 4 [μ-P(μ-N t Bu)] 2 (4), displays an unfolded open-face cavity area of 110.1 Å 2 . Preliminary theoretical host-guest studies with the dication [MeNC 5 H 4 ] 2 2+ suggest compound 4 as a viable candidate for the synthesis of hybrid proto-rotaxanes species based on phosphazane building blocks., (© 2022. The Author(s).)

Regular use of incense and earthen lamps in temples leads to the release of particulate matter (PM), airborne flecks, and gaseous pollutants. Similarly, the cremation of dead bodies using timber and other accessories such as incense, organic chemicals containing carbon, and clothes generates air pollutants. It is currently unclear how much emissions and exposure these activities may lead. This work attempts to fill this gap in our understanding by assessing the associated emissions of PM 2.5 and the corresponding exposure. Ten temples and two cremation grounds were considered for the sampling of PM 2.5 . The average PM 2.5 concentration at the ten temples and the two crematoriums was found to be 658.30 ± 112.63 µg/m 3 and 1043.50 ± 191.63 µg/m 3 , respectively. The range of real-time PM 2.5 data obtained from the nearest twelve stations located in the vicinity was 113-191 µg/m 3 . The exposure assessment in terms of deposition dose was carried out using the ICRP model. The maximum and minimum total respiratory deposition dose rate for PM 2.5 for temples was 175.75 µg/min and 101.15 µg/min, respectively. For crematoriums, the maximum and minimum value of same was 252.3 µg/min and 194.31 µg/min, respectively, for an exposure period of 10 min., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors. Long-term fluoxetine treatment results in hepatotoxicity. Baicalin, a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant, hepatoprotective and anti-inflammatory effects. However, the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported., Aim: To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation., Methods: Male albino Wistar rats were divided into seven groups. Group 1 was the normal control. Oral fluoxetine was administered at 10 mg/kg body weight to groups 2, 3, 4 and 5. In addition, groups 3 and 4 were also co-administered oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg), a standard hepatoprotective compound for comparison. Groups 6 and 7 were used as a positive control for baicalin (100 mg/kg) and silymarin (100 mg/kg), respectively. All treatments were carried out for 28 d. After sacrifice of the rats, biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), advanced oxidation protein products (AOPP), malondialdehyde (MDA)], and liver injury [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, bilirubin] were studied in serum and tissue using standard protocols and diagnostic kits. Inflammatory markers [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-10 and interferon (IFN)-γ] in serum were evaluated using ELISA-based kits. The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections., Results: Fluoxetine-treated rats showed elevated levels of the serum liver function markers (total bilirubin, ALT, AST, and ALP) and inflammatory markers (TNF-α, IL-6, IL-10 and IFN-γ), with a decline in total protein and albumin levels. Biochemical markers of oxidative stress such as SOD, CAT, GST, GSH, MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage. Histological examination of liver tissue also showed degeneration of hepatocytes. Concurrent administration of baicalin (50 and 100 mg/kg) restored the biomarkers of oxidative stress, inflammation and hepatic damage in serum as well as in liver tissues to near normal levels., Conclusion: These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Adenoid and tonsillar hypertrophy in children often leads to adverse respiratory symptoms and obstructive sleep apnea (OSA). Current clinical guidelines from the American Academy of Pediatrics and American Academy of Otolaryngology-Head and Neck Surgery recommend tonsillectomy as the first line of pediatric OSA treatment for children with tonsillar hypertrophy. Rapid palatal expansion (RPE) performed by orthodontists improves obstructive sleep apnea in children by reducing nasal airway resistance, increasing nasal volume, raising tongue posture, and enlarging pharyngeal airway. However, the role of RPE in alleviating adenoid and tonsillar hypertrophy remains elusive. In this study, we aim to evaluate the changes in adenoid and palatine tonsil sizes following RPE using 3D volumetric analysis of cone beam computational tomography (CBCT) imaging., Materials and Methods: In this retrospective cohort study, a total of 60 pediatric patients (mean age: 8.00, range: 5-15, 32 females and 28 males) who had tonsillar hypertrophy (size 3 and 4) were included and divided into the control group (n = 20) and expansion group (n = 40). The control group did not undergo any treatment. The expansion group underwent RPE using a conventional Hyrax expander, activated 0.25 mm per day for 4-6 weeks. Final CBCT scans (T2) were performed 13.8 ± 6.5 months after the initial scan (T1). Pediatric sleep questionnaire (PSQ) and BMI were obtained at each timepoint. Volumetric analysis of adenoid and palatine tonsils was performed using a combination of bony and soft tissue landmarks in CBCT scans through Anatomage Invivo 6 imaging software. Paired t-tests were used to evaluate the difference between the initial and final adenoid and tonsil volumes. p values less than 0.05 were considered statistically significant., Results: Compared to the control group, the expansion group experienced a statistically significant decrease in both adenoid and tonsil volume. There was non-statistically significant increase in volume from T1 to T2 for the control group. For the expansion group, 90.0% and 97.5% of patients experienced significant reduction in adenoid and tonsil volume, respectively. The average volume decrease of adenoids was 16.8% while that of tonsils was 38.5%. The patients had up to 51.6% and 75.4% reduction in adenoid and tonsil size, respectively, following RPE orthodontic treatment. Pearson correlation ranged from 0.88 to 0.99 for each measurement, representing excellent internal consistency. There was a significant reduction in the PSQ scores from 5.81 ± 3.31 to 3.75 ± 2.38 in expansion group (p < 0.001)., Conclusions: Our results demonstrated that RPE significantly reduced the size of both adenoid and palatine tonsils and revealed another long-term benefit of RPE treatment. To our knowledge, this is the first study to quantify the changes of adenoids and tonsils following RPE. RPE treatment can be considered as a valid and effective treatment option for pediatric OSA population with narrow high arch palate and adenotonsillar hypertrophy., (Copyright © 2022. Published by Elsevier B.V.)

Ruthenium complexes are being studied extensively as anticancer drugs following the inclusion of NAMI-A and KP1019 in phase II clinical trials for the treatment of metastatic phase and primary tumors. Herein, we designed and synthesized four organometallic Ru(II)-arene complexes [Ru(η 6 - p -cymene)(L)Cl] (1), [Ru(η 6 -benzene)(L)Cl] (2), [Ru(η 6 - p -cymene)(L)N 3 ] (3) and [Ru(η 6 -benzene)(L)N 3 ] (4) [HL = ( E )- N '-(pyren-1-ylmethylene)thiopene-2-carbohydrazide] that have anticancer, antimetastatic and two-photon cell imaging abilities. Moreover, in the transfer hydrogenation of NADH to NAD + , these compounds also display good catalytic activity. All the complexes, 1-4, are well characterized by spectroscopic techniques (NMR, mass, FTIR, UV-vis and fluorescence). The single crystal X-ray diffraction technique proved that the ligand L coordinates through an N,O-bidentate chelating fashion in the solid-state structures of complexes 1 and 2. The stability study of the complexes was performed through UV-visible spectroscopy. The cytotoxicities of all the complexes were screened through MTT assay and the results revealed that the complexes have potential anticancer activity against various cancerous cells (HeLa, MCF7 and A431). Studies with spectroscopic techniques revealed that complexes 1-4 exhibit strong interactions with biological molecules i.e. proteins (HSA and BSA) and CT-DNA. The density functional theory (DFT-D) method has been employed in the present study to know the interaction between DNA and complexes by calculating the HOMO and LUMO energy. A plausible mechanism for NADH oxidation has also been explored and the DFT calculations are found to be in accord with the experimental observation. Furthermore, we have investigated intracellular reactive oxygen species (ROS) generation capabilities in the MCF7 breast cancer cell line. The Hoechst/PI dual staining method confirmed the apoptosis mode of cell death. Meanwhile, complexes 1-4 show capabilities to prevent the metastasis phase of cancer cells by inhibiting cell migration.

Background: Longitudinal access to cerebrospinal fluid (CSF) is useful for biomarker discovery in neurological disorders or diseases affecting CSF composition. Here, we aim to test a new method for insertion of a permanent intrathecal catheter, facilitating longitudinal collection of CSF., New Method: We surgically placed a permanent intrathecal catheter into the cisterna magna of anesthetized neonatal piglets. The thecal sac was accessed at the L5-S1 spinal level and a radiopaque catheter was inserted under fluoroscopic x-ray guidance to position the tip at the cisterna magna. A titanium access port was connected to the catheter and anchored subcutaneously. Immediately after surgery, we confirmed CSF flow through the catheter and port via needle aspiration. Catheter patency over a two-month study period was determined through periodic CSF collection from the port., Results: Frequent (up to 3 times weekly), longitudinal sampling of CSF was achievable in neonatal piglets up to 60 days after implantation. CSF was readily accessible through the port without major adverse events. Catheterized piglets demonstrated slower, but normal, weight gain compared to control piglets. Post-operative complications were managed with standard access precautions and medications. There were no complications involving the implanted hardware., Comparison With Existing Method(s): This method fills a critical gap in the existing methods for longitudinal CSF sampling through an implanted intrathecal catheter system in neonatal piglets., Conclusions: This novel method is both safe and effective for longitudinal CSF access in the domestic piglet. Catheter patency and access to CSF is maintained over multiple months without major adverse events., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A set of metal carbonyl cluster-boronic acid conjugates of the group VIII metals (Fe, Ru, and Os) were synthesized and their antiproliferative effects measured against two breast cancer cell lines (MCF-7 and MDA-MB-231) and a noncancerous breast epithelial (MCF-10A) cell line. The cytotoxicity followed the order Ru > Os > Fe for the MDA-MB-231 cells, although the latter two exhibited similar cytotoxicity against MCF-7 and MCF-10A cells. The osmium species {Os 3 (CO) 10 (μ-H)[μ-SC 6 H 4 - p -B(OH) 2 ]} ( 2 ) could be chemically oxidized to its hydroxy analogue [Os 3 (CO) 10 (μ-H)(μ-SC 6 H 4 -p -OH)] ( 2-OH ), which showed comparable cytotoxicity. Mode of action studies pointed to an apoptotic pathway for cell death., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

We report a simple method for producing polymeric microparticles with controlled three-dimensional (3D) shapes from two-dimensional (2D) micromolds via mold geometry-mediated tunable mold swelling and capillarity. Specifically, the photocurable solution confined in the mold with diverse geometries is spatially deformed by the addition of the wetting fluid, which triggers the mold swelling and capillarity; this allows the production of highly uniform microparticles with complex shape via photopolymerization. The results show that the swelling-induced mold deflection is varied depending on the mold geometry with different side lengths, allowing a tunable deformation of the photocurable solution and forming non-spherical particles with a convex top. The capillarity of the wetting fluid is also determined by the mold geometry with different corner angles, leading to the directional movement of the photocurable solution via Laplace pressure-driven flow and facilitating the production of spherical particles with or without shape imprinting. Furthermore, we demonstrate a capability to further enhance the mold swelling by varying mold composition, expanding their controllability in 3D shape, and enabling simultaneous production of spherical and non-spherical particles using a single mold., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Long non-coding RNAs (lncRNAs) play key roles in Angiotensin II (AngII) signaling but their role in chondrogenic transformation of vascular smooth muscle cells (VSMCs) is unknown. We describe a novel AngII-induced lncRNA Alivec (Angiotensin II-induced lncRNA in VSMCs eliciting chondrogenic phenotype) implicated in VSMC chondrogenesis. In rat VSMCs, Alivec and the nearby gene Acan , a chondrogenic marker, were induced by growth factors AngII and PDGF and the inflammatory cytokine TNF-α. AngII co-regulated Alivec and Acan through the activation of AngII type1 receptor signaling and Sox9, a master transcriptional regulator of chondrogenesis. Alivec knockdown with GapmeR antisense-oligonucleotides attenuated the expression of AngII-induced chondrogenic marker genes, including Acan , and inhibited the chondrogenic phenotype of VSMCs. Conversely, Alivec overexpression upregulated these genes and promoted chondrogenic transformation. RNA-pulldown coupled to mass-spectrometry identified Tropomyosin-3-alpha and hnRNPA2B1 proteins as Alivec -binding proteins in VSMCs. Furthermore, male rats with AngII-driven hypertension showed increased aortic expression of Alivec and Acan . A putative human ortholog ALIVEC , was induced by AngII in human VSMCs, and this locus was found to harbor the quantitative trait loci affecting blood pressure. Together, these findings suggest that AngII-regulated lncRNA Alivec functions, at least in part, to mediate the AngII-induced chondrogenic transformation of VSMCs implicated in vascular dysfunction and hypertension.

Lipophile induced modulations of self-assembly characteristics in aqueous Pluronic systems merit attention because of wide-ranging uses of Pluronics as solubilizing agents of lipophilic substances. In this paper, we report unusual evolutions of structural and hydration properties in lavender essential oil (LO) solubilized Pluronic P85 aqueous micellar systems as a function of micellar volume fraction and temperature. Our DLS, SANS, and viscometry studies show that the spherical-to-wormlike micellar structural transition observed in 1% P85 solutions upon solubilization of LO quite unexpectedly gets suppressed with increased P85 concentration to ≥5%. Detailed SANS studies reveal that the core sizes of the oil solubilized micelles cannot attain the threshold value required for the onset of structural transition at higher copolymer concentrations due to their progressive shrinking with an increase in P85 concentration. Oil solubilized P85 solutions show two cloud points and very interestingly exhibit micellar growth upon cooling to their lower cloud points. Steady state fluorescence studies explain this based on increasing dehydration of micellar corona with a decrease in temperature, very much opposite to what is observed in pure aqueous Pluronic systems. The results give new insight into viscous flow properties and low temperature storage possibilities of oil solubilized aqueous Pluronic systems.

Amphiphilic diblock copolymers containing dopamine and zwitterions are synthesized via the RAFT polymerization method, which undergo temperature-mediated micellization in aqueous media. The presence of catechol moiety in dopamine is exploited to form pH-responsive cross-links with ferric ions (Fe 3+ ) at different pH value. Herein, a comprehensive study of the effect of pH as well as temperature on the size and solution behavior of these cross-linked micelles is presented. These micelles cross-linked via metal-catechol coordination bonds can have several important biomedical applications such as degradable scaffolds for payload delivery., (© 2021 Wiley-VCH GmbH.)

Importance: The rate of deaths from overdose has increased during the COVID-19 pandemic, and recent US overdose mortality rates have been markedly high. However, scant data are available on the causes of this increase or subpopulations at elevated risk., Objective: To evaluate the rates and characteristics of deaths from drug overdose before vs during the COVID-19 pandemic., Design, Setting, and Participants: This retrospective, population-based cohort study used data from 4 statewide databases linked at the person level via the Rhode Island Data Ecosystem on adults with deaths due to overdose in Rhode Island from January 1 to August 31, 2019, and January 1 to August 31, 2020., Main Outcomes and Measures: The rates of unintentional deaths from drug-related overdose during the 2019 and 2020 observation periods overall and by sociodemographic characteristics, drugs contributing to the cause of death, location of death, and socioeconomic factors were evaluated. In subgroup analyses restricted to Medicaid beneficiaries (n = 271), the proportions of deaths from overdose by behavioral health treatment and diagnosis claims in the year before death were also examined., Results: A total of 470 adults who died of drug overdose were included in the analysis (353 men [75%]; mean [SD] age, 43.5 [12.1] years). The rate of deaths from overdose in Rhode Island increased 28.1%, from 29.2 per 100 000 person-years in 2019 to 37.4 per 100 000 person-years in 2020 (P = .009). Compared with 2019, rates of deaths due to overdose during 2020 were higher among men (43.2 vs 59.2 per 100 000 person-years; P = .003), non-Hispanic White individuals (31.0 vs 42.0 per 100 000 person-years; P = .005), single individuals (54.8 vs 70.4 per 100 000 person-years; P = .04), deaths involving synthetic opioids (20.8 vs 28.3 per 100 000 person-years; P = .005), and deaths occurring in a personal residence (13.2 vs 19.7 per 100 000 person-years; P = .003). A decrease in the proportion of deaths from overdose involving heroin (11 of 206 [5%] vs <2% [exact value suppressed]; P = .02) and an increase among persons experiencing job loss (16 of 206 [8%] vs 41 of 264 [16%]; P = .01) from 2019 to 2020 were observed. Among individuals who died of overdose and were Medicaid beneficiaries, the proportions of those aged 50 to 59 years with anxiety (11 of 121 [9%] vs 29 of 150 [19%]; P = .03), men with depression (27 of 121 [22%] vs 57 of 150 [38%]; P = .008), and men with anxiety (28 of 121 [23%] vs 55 of 150 [37%]; P = .02) increased during 2020 compared with 2019., Conclusions and Relevance: In this cohort study, during the first 8 months of 2020, the rate of deaths from overdose increased in Rhode Island compared with the same period in 2019, and several emerging characteristics of deaths from drug overdose during the first year of the COVID-19 pandemic were identified. These findings may inform interventions that address macroenvironmental changes associated with the pandemic.

The ability to rationally design and predictably construct crystalline solids has been the hallmark of crystal engineering research. To date, numerous examples of multicomponent crystals comprising organic molecules have been reported. However, the crystal engineering of cocrystals comprising both organic and inorganic chemical units is still poorly understood and mostly unexplored. Here, we report a new diverse set of higher-order cocrystals (HOCs) based on the structurally versatile-yet largely unexplored-phosph(V/V)azane heterosynthon building block. The novel ternary and quaternary cocrystals reported are held together by synergistic and orthogonal intermolecular interactions. Notably, the HOCs can be readily obtained either via sequential or one-pot mechanochemical methods. Computational modelling methods reveal that the HOCs are thermodynamically driven to form and that their mechanical properties strongly depend on the composition and intermolecular forces in the crystal, offering untapped potential for optimizing material properties., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)