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The development of an environmentally benign method for the synthesis of nanoparticles has been facilitated by green chemistry. "Green synthesis" uses a range of biological elements like microbes, plants, and other biodegradable materials to produce NPs. Active biomolecules that are secreted by natural strains and present in the plant extracts serve as both reducing and capping/stabilizing agents. Microorganisms' intracellular enzymes can reduce metal ions, which explains how NPs might potentially nucleate. Plant-based synthesis of nanomaterials is particularly promising owing to abundant resources, simplicity of synthesis, and low cost. Silver nanoparticles (AgNPs) are attracting great attention in the research community due to their wide variety of applications in chemistry, food technology, microbiology, and biomedicine. Recent years have seen a large amount of research on the bio-genic synthesis of AgNPs employing biomaterials like plant extract and bacteria as reducing agents. Herein we discuss a thorough overview of the plant-based synthesis of silver nanoparticles (AgNPs), characterization approaches, applications, and toxicity. The review covers the green chemistry and nanotechnology elements of producing AgNPs, including a thorough discussion of the plant extract mediated synthesis, detailed formation mechanism, and a well-balanced emphasis on hazards and advantages. Based on current developments, the optimisation strategies, applications, and interdisciplinary characteristics are also covered in detail., 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 © 2024 Elsevier B.V. All rights reserved.)

Introduction: Rehabilitation after Total Knee Arthroplasty (TKA) often includes proprioceptive exercises to prevent falls, but studies on proprioceptive training have yielded conflicting findings. This study aims to explore impact of proprioceptive training on functional performance after TKA., Methods: Eighty patients who underwent unilateral TKA were randomly assigned to a proprioceptive exercise (PE) group or a routine exercises (RE) group. The PE group received proprioceptive exercises in addition to routine physiotherapy. Osteoarthritis Research Society Internal (OARSI) recommended tests and Oxford Knee Score (OKS) were used to assess performance and outcome at 3 and 6 months., Results: In the 30-s chair sits test, the PE group outperformed the RE group at 3 months (13.69 vs. 9.17) and 6 months (21.07 vs. 18.63) ( p  < 0.001 and p  = 0.030). Stair climbing favoured PE group at 3 months (8.86 vs. 16.66, p  = 0.037) and 6 months (0.556 vs. 1.133, p = 0.001). At 6 months in the 40-m fast-paced walk test, the PE group had a significantly shorter time (0.308 min vs. 0.557 min, p  < 0.001). Timed up and go test at 6 months favoured PE group (0.204 min vs. 0.377 min). In the 6-min walk test, the PE group covered significantly greater distances than the RE group at 3 months (589.59 vs. 346.53 m, p  < 0.001) and 6 months (649.60 vs. 448.32 m, p  < 0.001). OKS at 3 months was 38 ± 2.0 for PE group and 38 ± 4 for RE group ( p  = 1). OKS at 6 months was 42 ± 4 for PE group and 40 ± 2 for RE group ( p  = 0.94)., Conclusion: This study highlights the importance of proprioception-based rehabilitation in improving functional performance for TKA patients, surpassing traditional rehabilitation programmes., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© Indian Orthopaedics Association 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The average rate of patient dissatisfaction following total knee arthroplasty (TKA) is 10%. Multi-modal analgesia is the present standard of pain management after TKA. Studies show that with multi-modal analgesia, approximately 60% of patients experience severe knee pain following surgery, while around 30% experience moderate pain. To date, there is no literature available on targeted pain management using bone cement., Objectives: To investigate the feasibility of incorporating anti-inflammatory medications and identify the analgesic with the best release pharmacokinetics from bone cement for application in pain management., Methods: In an in-vitro study, 100 mg of five drugs (aceclofenac, diclofenac, naproxen, paracetamol and methyl prednisolone) were incorporated into bone cement (Palacos). Cement cubes holding each drug were made and allowed to harden for 30 min. Each drug-containing cube was placed in a beaker with saline for 72 h. Fractions of 10 ml were collected at 0, 6, 24, 48 and 72 h and analysed using high-pressure liquid chromatography to measure the percentage release of the drug from bone cement., Results: Naproxen showed superior elution from bone cement, with 10.9% at 24 h and 9.08% at 72 h. Paracetamol showed 4.9% at 24 h and 3.78% at 72 h, aceclofenac 0.2% at 24 h and 0.4% at 72 h, diclofenac 3.03% at 24 h and 1.99% at 72 h, and methylprednisolone 0.26% at 24 h and 0.32% at 72 h., Conclusions: Polymethylmethacrylate bone cement can elute analgesics in vitro. Among the five drugs studied, naproxen had the best release kinematics from polymethylmethacrylate bone cement. Analgesic eluting bone cement is a novel approach for targeted postoperative pain management in TKA., 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 © 2024 Elsevier B.V. All rights reserved.)

Study Background: Mechanical alignment has always been considered as the gold standard in total knee arthroplasty (TKA), but various other coronal alignment strategies have been proposed to enhance native knee kinematics and thus elevate patient satisfaction levels. Coronal plane alignment of the knee (CPAK) classification introduced by MacDessi is a simple yet comprehensive system to classify knees based on their coronal plane alignment. It categorizes knees into nine phenotypes based on medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA)., Materials and Methods: This study investigates the distribution of classification of primary arthritic knees (CPAK) types among arthritic knees in the South Indian population and compares the functional outcomes following total knee arthroplasty (TKA) using traditional mechanical alignment among various CPAK types. The research, spanning from September 2021 to August 2023, encompasses a comprehensive analysis of 324 patients with 352 knees in the first part and 48 patients with 72 knees in the second part of the study who underwent TKA, incorporating demographic data and radiological evaluations., Results: Results indicate a predominant distribution of CPAK type 1, followed by type 2 and type 4 among the South Indian population. In the functional outcomes analysis, regardless of CPAK type, patients exhibited significant improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), and visual analog scale (VAS) scores post-operatively., Conclusion: CPAK distribution among the South Indian population is comparable to other Indian study and studies with an Asian population, but varies with studies among the White population. Significant improvement of functional outcome among all CPAK types signifies the robust nature of conventional mechanical alignment strategy. Thus, our study serves as an initial exploration into the knee phenotype of the South Indian population and findings contribute to ongoing research on optimal alignment strategies in knee arthroplasty, paving the way for future, more extensive studies in this dynamic field., Competing Interests: Conflict of InterestWe the authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© Indian Orthopaedics Association 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Persistent anterior knee pain post total knee arthroplasty (TKA) is a significant cause of patient dissatisfaction. Selective patellar resurfacing is commonly practiced for primary total knee replacement (TKR) but there is a paucity in literature regarding its decision making., Study Objective: This study aims to develop a decision-making algorithm for selective patellar resurfacing using Hospital for Special Surgery Patello-femoral Assessment score (HSS PFA score), weight-bearing patellofemoral X-ray, and intraoperative cartilage wear assessment based on the Outerbridge classification., Materials and Methods: This prospective study enrolled 65 patients, assessing preoperative factors including HSS PFA score and Baldini view radiography. Intraoperative cartilage wear was categorized using the Outerbridge classification. Preoperative findings were correlated with intraoperative outcomes through statistical analysis, leading to the development of a predictive algorithm. The efficiency of algorithm was assessed at 3-year follow-up using HSS PFA score., Results: A significant negative correlation ( r  = - 0.272, p  = 0.029) was observed between HSS PFA score and cartilage wear. However, no significant relationships were established between HSS PFA score and Baldini view observations, including radiological tilt ( p  = 0.517) and displacement ( p  = 0.277). Intraoperative cartilage wear versus patellar tilt ( p  = 0.65) and displacement ( p  = 0.837) also yielded non-significant results. Three-year follow-up examinations revealed no complications and significant HSS PFA score improvements in all patients., Conclusion: The requirement for patellar resurfacing can be predicted using a combination of preoperative parameter such as HSS PFA score and the intra-operative cartilage wear. We put forward an algorithm based on above findings to aid in the decision making., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© Indian Orthopaedics Association 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The present experimental study aims to make advancements in the daily production of freshwater by a single solar still, with the ultimate goal of increasing its efficiency. The experiment was carried out in the solar still with and without integration at four different water masses within the basin, and metrics such as water, glass, basin temperature, and drinkable water generated were measured. The results showed that the daily distillate collected from the integrated system using 2.5 kg/h of mass flow in the parabolic concentrator produced 2.99 kg at the minimum water mass of 20 kg placed in the basin. When the flow velocity of water in the parabolic concentrator is raised from 2.5 to 5 kg/h, the amount of freshwater generated decreases from 2.99 to 2.66 kg. Compared to traditional single slope solar still, the potable water generated increases by roughly 18.24, 18.29, and 18.33% for water mass of 30, 40, and 50 kg, respectively, with the mass flow rate of water in the serpentine tubes as 2.5 kg/h. The results also reveals that, in addition to the PTC collector, the mass flowrate of fluid in the serpentine tube arrangement submerged in the basin affects daily solar efficiency. There is a significant reduction of about 1-2.3% in the daily efficiency of the system with increased mass flow rate of fluid in the serpentine tube arrangement. Similarly, the daily efficiency in all the cases reduces with increased water depth., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neural circuit formation and function require that diverse neurons are specified in appropriate numbers. Known strategies for controlling neuronal numbers involve regulating either cell proliferation or survival. We used the Drosophila visual system to probe how neuronal numbers are set. Photoreceptors from the eye-disc induce their target field, the lamina, such that for every unit eye there is a corresponding lamina unit (column). Although each column initially contains ~6 post-mitotic lamina precursors, only 5 differentiate into neurons, called L1-L5; the 'extra' precursor, which is invariantly positioned above the L5 neuron in each column, undergoes apoptosis. Here, we showed that a glial population called the outer chiasm giant glia (xg O ), which resides below the lamina, secretes multiple ligands to induce L5 differentiation in response to epidermal growth factor (EGF) from photoreceptors. By forcing neuronal differentiation in the lamina, we uncovered that though fated to die, the 'extra' precursor is specified as an L5. Therefore, two precursors are specified as L5s but only one differentiates during normal development. We found that the row of precursors nearest to xg O differentiate into L5s and, in turn, antagonise differentiation signalling to prevent the 'extra' precursors from differentiating, resulting in their death. Thus, an intricate interplay of glial signals and feedback from differentiating neurons defines an invariant and stereotyped pattern of neuronal differentiation and programmed cell death to ensure that lamina columns each contain exactly one L5 neuron., Competing Interests: AP, IL, MB, ZH No competing interests declared, VF Reviewing editor, eLife, (© 2022, Prasad et al.)

Defining the origin of neuronal diversity is a major challenge in developmental neurobiology. The Drosophila visual system is an excellent paradigm to study how cellular diversity is generated. Photoreceptors from the eye disc grow their axons into the optic lobe and secrete Hedgehog (Hh) to induce the lamina, such that for every unit eye there is a corresponding lamina unit made up of post-mitotic precursors stacked into columns. Each differentiated column contains five lamina neuron types (L1-L5), making it the simplest neuropil in the optic lobe, yet how this diversity is generated was unknown. Here, we found that Hh pathway activity is graded along the distal-proximal axis of lamina columns, and further determined that this gradient in pathway activity arises from a gradient of Hh ligand. We manipulated Hh pathway activity cell autonomously in lamina precursors and non-cell autonomously by inactivating the Hh ligand and by knocking it down in photoreceptors. These manipulations showed that different thresholds of activity specify unique cell identities, with more proximal cell types specified in response to progressively lower Hh levels. Thus, our data establish that Hh acts as a morphogen to pattern the lamina. Although this is the first such report during Drosophila nervous system development, our work uncovers a remarkable similarity with the vertebrate neural tube, which is patterned by Sonic Hh. Altogether, we show that differentiating neurons can regulate the neuronal diversity of their distant target fields through morphogen gradients., Competing Interests: MB, AP, AD No competing interests declared, VF Reviewing editor, eLife, (© 2022, Bostock et al.)

The availability of drinkable water, along with food and air, is a fundamental human necessity. Because of the presence of higher amounts of salt and pollution, direct use of water from sources such as lakes, sea, rivers, and subsurface water reservoirs is not normally suggested. Solar is still a basic technology that can use solar energy to transform accessible waste or brackish water into drinkable water. Exergy analysis is a strong inferential technique for evaluating the performance of thermal systems. Exergy is becoming more popular as a predictive tool for analysis, and there is a rising interest in using it. In this paper, performance analysis on the aspect of energy and exergy from the proposed solar still (PSS) (conventional solar still with the photovoltaic modules-AC heater) was analyzed on three different water depths (W d ) conditions (1, 2, and 3 cm). Using a solar still with an electric heater, the daily potable water production was found as 8.54, 6.37, and 4.43 kg, for the variations in water depth (W d ) of 1, 2, and 3 cm respectively. The energy and exergy efficiency of the PSS at the W d of 1, 2, and 3 cm were 75.67, 51.45, and 37.21% and 5.08, 2.29, and 1.03%, respectively. At 1 cm W d , PSS produced the maximum freshwater yield as compared to the other two water depths. When the W d is increased from 1 to 2 cm and from 1 to 3 cm, the yield is decreased up to 27.3 and 52.7%, respectively. Similarly, the energy and exergy efficiency is decreased up to 36.8 and 53.2% and 50.4 and 80.6%, respectively. The water cost of the modified solar still is calculated as 0.028 $/kg for the least water thickness., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Extracellular signal-regulated kinase (ERK) lies downstream of a core signalling cascade that controls all aspects of development and adult homeostasis. Recent developments have led to new tools to image and manipulate the pathway. However, visualising ERK activity in vivo with high temporal resolution remains a challenge in Drosophila. We adapted a kinase translocation reporter (KTR) for use in Drosophila, which shuttles out of the nucleus when phosphorylated by ERK. We show that ERK-KTR faithfully reports endogenous ERK signalling activity in developing and adult tissues, and that it responds to genetic perturbations upstream of ERK. Using ERK-KTR in time-lapse imaging, we made two novel observations: firstly, sustained hyperactivation of ERK by expression of dominant-active epidermal growth factor receptor raised the overall level but did not alter the kinetics of ERK activity; secondly, the direction of migration of retinal basal glia correlated with their ERK activity levels, suggesting an explanation for the heterogeneity in ERK activity observed in fixed tissue. Our results show that KTR technology can be applied in Drosophila to monitor ERK activity in real-time and suggest that this modular tool can be further adapted to study other kinases. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Cholesterol is synthesized in chicken through de novo lipid biosynthetic pathway where two most important genes viz. SREBP1 and ACACA play immense role. To minimize cholesterol synthesis, RNAi approach was adopted and accordingly, we developed transgenic chicken possessing ACACA and SREBP1 shRNA constructs, which showed lower level of ACACA and SREBP1 in serum. The serum total cholesterol, triglycerides, HDL and LDL cholesterol was significantly lower by 23.8, 35.6, 26.6 and 20.9%, respectively in SREBP1 transgenic birds compared to the control. The egg total cholesterol and LDL cholesterol content was numerically lower in both ACACA and SREBP1 transgenic birds by 14.3 and 13.2%, and 10.4 and 13.7%, respectively compared to the control. It is concluded that the protocol was perfected to develop transgenic chicken through RNAi for knocking down the expression of ACACA and SREBP1 proteins, which minimized the cholesterol and triglycerides contents in serum and eggs., (© 2022. The Author(s).)

In this work, a new attempt was made to study the behavior of the conventional solar still (CSS) by adding a black-painted copper plate and phosphate pellets. Therefore, the performance of the three solar stills has been studied and compared. The first is the CSS, and the second is the modified solar still (MSS). The MSS performance was tested using black-coated copper plate (measuring 49 × 49 cm and 0.2 cm thick) with and without phosphate pellets and compared to the CSS in the similar climatic conditions. The results showed that the combination of black coated copper plate and the inclusion of phosphate pellets improved the evaporation rate and daily productivity. During the experiments, yields using black coated copper plate without and with phosphate pellets were 14.96% and 29.53% greater than the CSS. The effectiveness of the CSS, MSS with copper metal plate (MSS-CP), and MSS with copper metal plate with phosphate pellets (MSS-CP and PP) are around 30.23, 35.3, and 41.44%, respectively., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The photovoltaic (PV) for irrigation system is an emerging technology to harness the solar energy. The performance of the PV modules depends on the incident solar radiation, geographical location, and the surface temperature of the modules. The performance of the PV system needs to be monitored by manually or embedded controllers. The commercially available technologies for monitoring the system are costlier and need to be optimized. The Arduino controller is used to monitor the performance of the photovoltaic (PV) system in Coimbatore (11.016° N, 76.9558° E), Tamilnadu, India. The PV surface temperature is monitored and controlled by flowing the water above the module by setting the mean ambient temperature as a reference temperature 34 °C when the system exceeds the reference temperature. PV surface temperature is reduced up to 16°C thus improved the electrical efficiency by 17% compare to the reference module. The Arduino controller control the relay to switch on the motor to control the mass flow rate of the water at 0.0028kg/s. The various parameters are measured such as voltage, current, and solar radiation of the location and analyzed. The estimated cost of monitoring system and various sensor is 10$ which cost comparatively 50% lower than the other PV monitoring controllers. This method can be employed in the medium and large-scale irrigation system., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study details the intra-operative complications, and compares auditory scales post-implantation of either profoundly deaf young children with radiologically normal inner ears (group A) or children with Mondini dysplasia (group B)., Methods: A retrospective survey was carried out of 338 patients with severe to profound sensorineural hearing loss who underwent cochlear implant surgery from February 2015 to May 2017. Patients were divided into 2 groups of 27 patients each. Both groups were followed up to three years post-implantation., Results: Cerebrospinal fluid ooze developed in 12 patients, and 2 patients had a cerebrospinal fluid 'gusher', one of which had to be explored within 24 hours. After implant use for one year, both groups had similar speech perception scores., Conclusion: The cerebrospinal fluid gusher in Mondini dysplasia should be anticipated and adequately managed intra-operatively. This study highlights the tailoring of a post-implantation rehabilitation programme according to individual needs.

Time-lapse imaging is an essential tool to study dynamic biological processes that cannot be discerned from fixed samples alone. However, imaging cell- and tissue-level processes in intact animals poses numerous challenges if the organism is opaque and/or motile. Explant cultures of intact tissues circumvent some of these challenges, but sample drift remains a considerable obstacle. We employed a simple yet effective technique to immobilize tissues in medium-bathed agarose. We applied this technique to study multiple Drosophila tissues from first-instar larvae to adult stages in various orientations and with no evidence of anisotropic pressure or stress damage. Using this method, we were able to image fine features for up to 18 h and make novel observations. Specifically, we report that fibers characteristic of quiescent neuroblasts are inherited by their basal daughters during reactivation; that the lamina in the developing visual system is assembled roughly 2-3 columns at a time; that lamina glia positions are dynamic during development; and that the nuclear envelopes of adult testis cyst stem cells do not break down completely during mitosis. In all, we demonstrate that our protocol is well-suited for tissue immobilization and long-term live imaging, enabling new insights into tissue and cell dynamics in Drosophila ., (Copyright © 2020 Bostock, Prasad, Chaouni, Yuen, Sousa-Nunes, Amoyel and Fernandes.)

A bidentate Schiff base ligand, MHMMT, obtained from 1,2,4-triazine derivative and 4-hydroxy-3-methoxy benzaldehyde and its Fe(III), Co(II), Ni(II), Cu(II), and Zn(II) complexes were synthesised in ethanolic media and characterized by various analytical techniques like elemental analyses, magnetic susceptibility measurements, FTIR, UV-VIS, proton NMR, ESR, spectroscopic and thermogravimetric studies. Various geometries like a tetrahedral for Co(II) and Zn(II) complexes, an octahedral for Fe(III) and Ni(II) complexes, and square planar for Cu(II) complex has been assigned. For all metals complexes except Co(II), a 2:1 ligand to metal ratio is observed, while Co(II) complex has a 1:1 ratio. In accordance with the probable activity spectra of substances as obtained from PASS analysis, in vitro α-amylase inhibition studies by starch-iodine method for ligand and complexes except that of Fe(III) and anticancer screening against human breast cancer cell lines MCF-7 using MTT assay for Fe(III) complex were conducted. The tested compounds were found to be good α-amylase inhibitors, characteristically similar to most of the antidiabetic drugs. Among the compounds, Cu(II) complex exhibited the highest α-amylase inhibitory activity. Furthermore, ligand and complexes were also exposed to in vitro antimicrobial activities, drug-likeness, bioactivity score prediction by Molinspiration software. Molecular docking analysis of selected compounds on α-amylase and VEGFR-2 kinase were carried out for confirming the experimental observations., (© 2020 Published by Elsevier Ltd.)

Diabetic control through the inhibition of carbohydrate hydrolysing enzymes is established as an effective strategy. Many of the inorganic materials have already been investigated as enzyme inhibitors. Present study investigates the in-vitro antidiabetic activity of ZnO nanoparticles assessing their inhibition efficiency on α-glucosidase and α-amylase. The nanoparticles obtained with average dimeson of 11, 32 and 49 nm via green strategy were subjected to in-vitro antidiabetic assays. The samples were particularly selective for α-glucosidase while very mild inhibitors for α-amylase. ZnO sample with particle dimension of 32 nm was found to be the most potent inhibitor capable of preventing 97.86% enzymatic action. The IC50, and CC50 values of the sample were determined as 1.24 μg/mL and 88.89 μg/mL respectively. The selectivity index (SI) value obtained is 71.68 which indicates good selectivity towards enzymes inhibition rather than the host body. Molecular docking models were generated for ZnO association with α-glucosidase and possible binding sites were recognized., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present study was formulated to characterize and comprehend the molecular structural characteristics of ACTRIIB receptor in Aseel and control broiler (CB) populations. The full length coding sequence (1539 bp) of the receptor was amplified, cloned, sequenced and analyzed using bioinformatic tools. The physico chemical properties of protein and structural features like secondary structure, solvent accessibility and disorder regions were computed. The 3D structure was predicted by I-TASSER and evaluated by Ramachandran Plot and tools under Structural Analysis and Verification Server. The nucleotides differences between CB and Aseel were c. [156G > A; 210 T > C; 493C > T; c.520G > C; 665A > C; 686G > A; 937C > G; 1011A > C; 1130A > G; 1208 T > A; 1326 T > C; 1433 T > C]. The amino acid substitutions between CB and Aseel were p. [(Pro165Ser; Glu174Gln; Gln222Pro; Ser229Asn; His313Asp; Gln377Arg; Val403Asp; and Ile478Thr)]. While, the silent changes includes p. [(Lys53=; Glu71=; Leu337=; Asp442=)]. The molecular weight of mature protein was predicted to be 55.51 kDa and 57.80 kDa in Aseel and CB, respectively. The higher rank 3D model had a C-score of -1.60 in Aseel and - 1.41 in CB, while the estimated TM-score (0.54 ± 0.14) and RMSD (5.8 ± 1.2 Å) were found to be similar in Aseel and CB. Among the 512 residues, >90% were in favored region, 4.7% in allowed region and <1.5% in disallowed region in both Aseel and CB. The pattern of contact map was comparable in Aseel and CB. The Hydrogen bond plots of the Aseel and CB shared similar secondary structure pattern. The ACTRIIB protein was predicted to interact with ACVR1B, ACVR1C, INHBA, SMAD 1,2,5,7 & 9 and BMPR1A&B. Clustal and phylogenetic analysis implied that both the lines were closely related and formed a sub cluster with in avian cluster. The current research provides insights about structural and functional aspects of the receptor and also aids in understanding the evolutionary history of ACTRIIB., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Gene silencing by RNA interference is extensively used reverse genetic approach to analyse the implications of any gene in mammalian systems. The silencing of the Activin type IIB receptor belonging to transforming growth factor beta superfamily has demonstrated increase in muscle growth in many species. We designed five short hairpin RNA constructs targeting coding region of chicken ACTRIIB. All the shRNAs were transfected into chicken embryo fibroblast cells and evaluated their silencing efficiency by real time PCR and western blotting. Initially the computational analysis of target region and shRNA constructs was undertaken to predict sequence based features (secondary structures, GC% and H-b index) and thermodynamic features (ΔG overall , ΔG duplex , ΔG break-target , ΔG intra-oligomer , ΔG inter-oligomer and ΔΔG ends ). We determined that all these predicted features were associated with shRNA efficacy. The invitro analysis of shRNA constructs exhibited significant (P < 0.05) reduction in the levels of ACTRIIB at mRNA and protein level. The knock down efficiency of shRNAs varied significantly (P < 0.001) from 83% (shRNA 1) to 43% (shRNA 5). All the shRNAs up regulated the myogenic pathway associated genes (MyoD and MyoG) significantly (P < 0.05). There was significant (P < 0.05) up-regulation of IFNA, IFNB and MHCII transcripts. The ACTRIIB expression was inversely associated with the expression of myogenic pathway and immune response genes. The anti ACTRIIB shRNA construct 1 and 3 exhibited maximum knock down efficiency with minimal interferon response, and can be used for generating ACTRIIB knockdown chicken with higher muscle mass.

Alcaligenes sp. HPC 1271 demonstrated antibacterial activity against multidrug resistant bacteria, Enterobacter sp., resistant to sulfamethoxazole, ampicillin, azithromycin, and tetracycline, as well as against Serratia sp. GMX1, resistant to the same antibiotics with the addition of netilmicin. The cell-free culture supernatant was analyzed for possible antibacterials by HPLC, and the active fraction was further identified by LC-MS. Results suggest the production of tunicamycin, a nucleoside antibiotic. The draft genome of this bacterial isolate was analyzed, and the 4.2 Mb sequence data revealed six secondary metabolite-producing clusters, identified using antiSMASH platform as ectoine, butyrolactone, phosphonate, terpene, polyketides, and nonribosomal peptide synthase (NRPS). Additionally, the draft genome demonstrated homology to the tunicamycin-producing gene cluster and also defined 30 ORFs linked to protein secretion that could also play a role in the antibacterial activity observed. Gene expression analysis demonstrated that both NRPS and dTDP-glucose 4,6-dehydratase gene clusters are functional and could be involved in antibacterial biosynthesis.

Objective: To develop a quantitative histopathology algorithm to predict which patients with cutaneous squamous cell carcinoma (cSCC) were likely to experience recurrence or metastases., Study Design: This retrospective study of cSCC lesions compared patients with aggressive disease (n = 40) and those with nonaggressive disease (n = 35). Based on a previous study using nuclear karyometry, we determined that aggressive lesions had a high proportion of a specific nuclear phenotype. The proportion of those nuclei was used to derive an aggressiveness score for each lesion. The mean age of patients was similar in both groups, as were the locations of index lesions., Results: The mean aggressiveness scorefor cases with aggressive lesions was 0.60 ± 0.21 and was 0.28 ± 0.35 for those with nonaggressive lesions. The overall accuracy in properly characterizing lesions was 72%. The area under the receiver operating characteristic curve was 0.80 ± 0.05. In general, the aggressive nuclear phenotype is represented by elevated levels of chromatin clumps and short linear segments of dark chromatin/intense pixels., Conclusion: These data suggest that discriminant functions may be utilized to distinguish between aggressive and nonaggressive lesions at the time of diagnosis.

Aim: To investigate the close parallels between our novel diet-related mouse model of colon cancer and human colon cancer., Methods: Twenty-two wild-type female mice (ages 6-8 wk) were fed the standard control diet (AIN-93G) and an additional 22 female mice (ages 6-8 wk) were fed the control diet supplemented with 0.2% deoxycholic acid [diet + deoxycholic acid (DOC)] for 10 mo. Tumors occurred in the colons of mice fed diet + DOC and showed progression to colon cancer [adenocarcinoma (AC)]. This progression is through the stages of tubular adenoma (TA), TA with high grade dysplasia or adenoma with sessile serrated morphology, intramucosal AC, AC stage T1, and AC stage T2. The mouse tumors were compared to human tumors at the same stages by histopathological analysis. Sections of the small and large intestines of mice and humans were evaluated for glandular architecture, cellular and nuclear morphology including cellular orientation, cellular and nuclear atypia, pleomorphism, mitotic activity, frequency of goblet cells, crypt architecture, ulceration, penetration of crypts through the muscularis mucosa and presence of malignant crypts in the muscularis propria. In addition, preserved colonic tissues from genetically similar male mice, obtained from a prior experiment, were analyzed by immunohistochemistry. The male mice had been fed the control diet or diet + DOC. Four molecular markers were evaluated: 8-OH-dG, DNA repair protein ERCC1, autophagy protein beclin-1 and the nuclear location of beta-catenin in the stem cell region of crypts. Also, male mice fed diet + DOC plus 0.007% chlorogenic acid (diet + DOC + CGA) were evaluated for ERCC1, beclin-1 and nuclear location of beta-catenin., Results: Humans with high levels of diet-related DOC in their colons are at a substantially increased risk of developing colon cancer. The mice fed diet + DOC had levels of DOC in their colons comparable to that of humans on a high fat diet. The 22 mice without added DOC in their diet had no colonic tumors while 20 of the 22 mice (91%) fed diet + DOC developed colonic tumors. Furthermore, the tumors in 10 of these mice (45% of mice) included an adenocarcinoma. All mice were free of cancers of the small intestine. Histopathologically, the colonic tumor types in the mice were virtually identical to those in humans. In humans, characteristic aberrant changes in molecular markers can be detected both in field defects surrounding cancers (from which cancers arise) and within cancers. In the colonic tissues of mice fed diet + DOC similar changes in biomarkers appeared to occur. Thus, 8-OH-dG was increased, DNA repair protein ERCC1 was decreased, autophagy protein beclin-1 was increased and, in the stem cell region at the base of crypts there was substantial nuclear localization of beta-catenin as well as increased cytoplasmic beta-catenin. However, in mice fed diet + DOC + CGA (with reduced frequency of cancer) and evaluated for ERCC1, beclin-1, and beta-catenin in the stem cell region of crypts, mouse tissue showed amelioration of the aberrancies, suggesting that chlorogenic acid is protective at the molecular level against colon cancer. This is the first diet-related model of colon cancer that closely parallels human progression to colon cancer, both at the histomorphological level as well as in its molecular profile., Conclusion: The diet-related mouse model of colon cancer parallels progression to colon cancer in humans, and should be uniquely useful in model studies of prevention and therapeutics.

A field defect is a field of pre-malignant tissue in which a new cancer is likely to arise. Field defects often appear to be histologically normal under the microscope. Recent research indicates that cells within a field defect characteristically have an increased frequency of epigenetic alterations and these may be fundamentally important as underlying factors in progression to cancer. However, understanding of epigenetic field defects is at an early stage, and the work of Katsurano et al published this year, is a key contribution to this field. One question examined by Katsurano et al was how early could the formation of an epigenetic field defect be detected in a mouse colitis model of tumorigenesis. They highlighted a number of measurable epigenetic alterations, detected very early in normal appearing tissue undergoing histologically invisible tumorigenesis. They also documented the increasing presence of the epigenetic alterations at successive times during progression to cancer. In this commentary, we offer a perspective on the changes they observed within a broader sequence of epigenetic events that occur in progression to cancer. In particular, we highlight the likely central role of epigenetic deficiencies in DNA repair gene expression that arise during progression to cancer.

Purpose: This article makes an attempt to synthesize certain compounds containing thiazole and imidazole moieties and screen for the antimicrobial properties., Methods: The novel compounds synthesized were characterized by elemental analysis, IR and (1)HNMR spectral data. The antimicrobial activity of novel compounds was evaluated by cup plate method., Results: The compound p-t showed more antibacterial activity than that of the standard. p-hp and p-as showed considerable antibacterial activity. p-t demonstrated higher antifungal activity than that of the standard while p-hp and p-as showed considerable antifungal activity., Conclusion: The antimicrobial activity studies were conducted on certain selected bacteria and fungi. In each case antimicrobial activity of the compounds was compared with that of standards. p-t, p-hp, p-np, p-cp, p-ts and p-as showed considerable antimicrobial activity.

Purpose: The aim of this article is to synthesize, characterize and evaluate the antimicrobial activity of certain novel 3-methyl-5-oxo-4-(phenyl hydrazono)-4,5-dihydro-pyrazol-1-yl]-acetic acid N|-(4-substituted thiazol-2-yl)-hydrazides., Methods: The synthesized compounds were characterized by elemental analysis and IR, NMR and mass spectral data. The antimicrobial activity of novel compounds was evaluated by broth dilution method., Results: XVe, XVf and XVg have shown better antibacterial activity than other compounds of the series. XVa, XVc, XVd and XVe have shown better antifungal activity than the other compounds of the series., Conclusion: All compounds were found to exhibit fair degree of antimicrobial activity.

Background: Cancers often arise within an area of cells (e.g. an epithelial patch) that is predisposed to the development of cancer, i.e. a "field of cancerization" or "field defect." Sporadic colon cancer is characterized by an elevated mutation rate and genomic instability. If a field defect were deficient in DNA repair, DNA damages would tend to escape repair and give rise to carcinogenic mutations., Purpose: To determine whether reduced expression of DNA repair proteins Pms2, Ercc1 and Xpf (pairing partner of Ercc1) are early steps in progression to colon cancer., Results: Tissue biopsies were taken during colonoscopies of 77 patients at 4 different risk levels for colon cancer, including 19 patients who had never had colonic neoplasia (who served as controls). In addition, 158 tissue samples were taken from tissues near or within colon cancers removed by resection and 16 tissue samples were taken near tubulovillous adenomas (TVAs) removed by resection. 568 triplicate tissue sections (a total of 1,704 tissue sections) from these tissue samples were evaluated by immunohistochemistry for 4 DNA repair proteins. Substantially reduced protein expression of Pms2, Ercc1 and Xpf occurred in field defects of up to 10 cm longitudinally distant from colon cancers or TVAs and within colon cancers. Expression of another DNA repair protein, Ku86, was infrequently reduced in these areas. When Pms2, Ercc1 or Xpf were reduced in protein expression, then either one or both of the other two proteins most often had reduced protein expression as well. The mean inner colon circumferences, from 32 resections, of the ascending, transverse and descending/sigmoid areas were measured as 6.6 cm, 5.8 cm and 6.3 cm, respectively. When combined with other measurements in the literature, this indicates the approximate mean number of colonic crypts in humans is 10 million., Conclusions: The substantial deficiencies in protein expression of DNA repair proteins Pms2, Ercc1 and Xpf in about 1 million crypts near cancers and TVAs suggests that the tumors arose in field defects that were deficient in DNA repair and that deficiencies in Pms2, Ercc1 and Xpf are early steps, often occurring together, in progression to colon cancer.