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Currently, there are many uses of metal complexes, especially in the fields of medicinal chemistry and catalysis. Thus, fabrication of new complexes which perform as a catalyst and chemotherapeutic drug is always a beneficial addition to the literature. Herein, we report three heterocyclic thiosemicarbazone-based Pd(II) complexes [Pd(HL1)Cl] (C1), [Pd(L2)(PPh3)] (C2) and [Pd(L3)(PPh3)]Cl (C3) having coligands Cl and PPh3. Thiosemicarbazone ligands (H2L1, H2L2 and HL3) and the complexes (C1–C3) were characterized methodically using several spectroscopic techniques. Single-crystal X-ray diffraction methods reveal that the structural environment around the metal center of C2 is square planar, while for C1 and C3 it is a slighty distorted square plane. The supramolecular network of compounds was built via hydrogen bonds, C–H⋯π and π⋯π interactions. Density functional theory (DFT) study of the structure of the complexes supports experimental findings. The application of these complexes as catalysts toward Suzuki–Miyaura coupling reactions has been examined with various aryl halides and phenyl boronic acid in PEG 400 solvent. The complexes displayed good biomolecular interactions with DNA/protein, with a binding constant value of the order of 105 M−1. C3 showed greater binding efficacy toward these biomolecules than the other complexes, which might be due to the cationic nature of C3. Furthermore, antitumor activity of the complexes was studied against the human triple-negative breast cancer (TNBC) cell line MDA-MB-231. It was found that C3 was more toxic (IC50 = 10 ± 2.90 μM) toward MDA-MB-231 cells than the other complexes. A known chemotherapeutic drug, 5-fluorouracil, was included as positive control. The programmed cell death mechanism of C3 was confirmed. Additionally, complex-induced apoptosis was confirmed and occurred via a mitochondria-dependent (intrinsic) pathway. [ABSTRACT FROM AUTHOR]

As in most plants, during their growth from immature to mature stages, the leaves of Setaria viridis, a model C4 bioenergy plant, have differential growth rates from the base (immature or growing) to the tip (most mature). In this study, we constructed a multi-segment C4 leaf metabolic model of S. viridis with two cell types (bundle sheath and mesophyll cells) across four leaf segments (base to tip). We incorporated differential growth rates for each leaf segment as constraints and integrated transcriptomic data as the objective function for our model simulation using flux balance analysis. The model was able to predict the exchanges of metabolites between immature and mature segments of the leaf and the distribution of the activities of biomass synthesis across those segments. Our model demonstrated the use of a modelling approach in studying the source–sink relationship within an organ and provided insights into the metabolic interactions across different parts of a leaf. [ABSTRACT FROM AUTHOR]

MIL‐STD 1530D requires that the certification of an aircraft part employ analytical tools that are capable of modeling crack growth. It is further stated that the durability and damage tolerance (DADT) analyses should be based on linear elastic fracture mechanics (LEFM) and follow a building block approach. This paper illustrates the durability analysis required to certify an additively manufactured part by using the examples of durability tests performed on two wire arc additively manufactured (WAAM) 18Ni 250 Maraging steel specimens. Highlights: Examines the growth cracks in WAAM 18Ni 250 maraging steel specimens with rough surfaces.Reveals that cracking in specimens with rough surfaces is characterized by a single equation.Illustrates the Hartman–Schijve equation for assessing specimens with rough surfaces. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic performance of preoperative application of the Enzian classification (cEnzian) using surgical findings as reference standard. Design: A prospective international non‐interventional study. Setting: Twelve endometriosis centres in four European countries (Austria, Germany, Switzerland and Czech Republic). Population: 1062 women with endometriosis surgery. Methods: Extent of endometriosis was preoperatively classified using the cEnzian classification based on gynaecological examination and/or transvaginal ultrasound (TVS) and/or magnetic resonance imaging (MRI). After subsequent surgery, the surgeon classified the intraoperative findings using the Enzian classification. Main outcome measures: Sensitivity, specificity, PPV, NPV, LR+, LR− and accuracy were calculated. Conditional frequencies of intraoperative Enzian codings and the corresponding 95% confidence intervals were computed for each preoperative coding and visualised in plots. Results: Although overall consistency of cEnzian and Enzian was poor (35.14%, 95% confidence interval 32.26–38.03), high specificities and negative predictive values (NPVs) of the cEnzian compartments could be demonstrated. Looking at the individual parts of the Enzian classification, the poorest diagnostic performance was detected for compartment B and the highest PPVs were found for category 3 lesions (>3 cm), independent of the compartment. Conclusions: Using the Enzian classification in a non‐invasive setting is a useful tool providing us with an 'at a glance' summary of the diagnostic workup regarding deep endometriosis with high specificities and NPVs. An attempt to merge the two new endometriosis classification systems (#Enzian and AAGL 2021) seems reasonable taking into consideration the respective advantages of each other. The Enzian classification is a useful tool for an 'at a glance' description of preoperative workup regarding DE. [ABSTRACT FROM AUTHOR]

Monitoring habitat fragmentation (HF) for economically significant species at close-ranges can provide crucial data for deriving the indicators of the Sustainable Development Goals (SDG) 14.4 for complex socio-ecological systems such as coastal lagoons. However, exclusivity of local-scale processes causing fragmentation, differences in the monitoring approaches, differential interpretations of resilience to disasters, as well as mismatches in reporting outcomes of scientific studies indicate the need for a focussed monitoring framework for transitional ecosystems. Using the example of penaeid prawns (Peneaus sp.), an economically important species from Pulicat lagoon, (an intertidal ecosystem on the east coast of India), the present work presents the development of a practical framework using selective but effective indicators of HF. The overall approach involves establishment of baselines, causal loops, triggering transformations as well as adaptive responses as per the scale and magnitude of HF. In the context of deriving baselines (Level 1), in-situ indicators such as salinity, turbidity, chlorophyll-a concentrations and distribution of seagrass which directly influence the habitat selection are proposed. Derived datasets on nutrient budgets, changes in abundances, Representative Concentration Pathways scenarios 4.5 and 8.5 for climate-induced changes are proposed as external forcings to understand the causative parameters (Level 2). Monitoring extents of tidal influence in ecosystem-based approach for disaster risk reduction (EcoDRR) is proposed to evaluate triggers and adaptive responses (Level 3). The EcoDRR based framework presented has the potential to contribute towards policy-targeted transformative approaches relevant to India's National Fisheries Policy 2020 as well as SDG 14, cross-correlated with targets of other SDGs. [Display omitted] • New ecosystem-based modelling framework for transitional coastal lagoon ecosystems • Methodologies to assess evidence and extent of fragmentation at species-level • Eco-DRR and Red List of Ecosystems framework for upscaling to ecosystem-level • Example of Pulicat lagoon ecosystem, South-east coast of India [ABSTRACT FROM AUTHOR]

It is observed that a significant number of reactions are stoichiometrically unbalanced in the existing databases (e.g. MetaCyc), even in curated databases like RiceCyc. To obtain a valid model, reactions should be mass balanced. Here, we propose a systematic algorithm based on generalized inverse matrix - to search all the reactions where mass is not conserved and to calculate the appropriate balancing coefficients of reactants and products, wherever possible (feasible reactions). Using this algorithm we have identified the set of reactions which cannot be stoichiometrically balanced with the present set of substrates and products (infeasible reactions). We have also suggested names of filler metabolites to turn infeasible reactions into feasible reactions. [ABSTRACT FROM AUTHOR]

Precise control of protein and messenger RNA (mRNA) degradation is essential for cellular metabolism and homeostasis. Controlled and specific degradation of both molecular species necessitates their engagements with the respective degradation machineries; this engagement involves a disordered/unstructured segment of the substrate traversing the degradation tunnel of the machinery and accessing the catalytic sites. However, while molecular factors influencing protein degradation have been extensively explored on a genome scale, and in multiple organisms, such a comprehensive understanding remains missing for mRNAs. Here, we analyzed multiple genome‐scale experimental yeast mRNA half‐life data in light of experimentally derived mRNA secondary structures and protein binding data, along with high‐resolution X‐ray crystallographic structures of the RNase machines. Results unraveled a consistent genome‐scale trend that mRNAs comprising longer terminal and/or internal unstructured segments have significantly shorter half‐lives; the lengths of the 5′‐terminal, 3′‐terminal, and internal unstructured segments that affect mRNA half‐life are compatible with molecular structures of the 5′ exo‐, 3′ exo‐, and endoribonuclease machineries. Sequestration into ribonucleoprotein complexes elongates mRNA half‐life, presumably by burying ribonuclease engagement sites under oligomeric interfaces. After gene duplication, differences in terminal unstructured lengths, proportions of internal unstructured segments, and oligomerization modes result in significantly altered half‐lives of paralogous mRNAs. Side‐by‐side comparison of molecular principles underlying controlled protein and mRNA degradation in yeast unravels their remarkable mechanistic similarities and suggests how the intrinsic structural features of the two molecular species, at two different levels of the central dogma, regulate their half‐lives on genome scale. [ABSTRACT FROM AUTHOR]

Background: Endometriosis can be associated with considerable pain and sterility. After surgical excision of moderate or severe endometriosis lesions, the rate of recurrence reaches up to 67%. The objective of this retrospective study was to establish the recurrence and pregnancy rates following surgical resection of stage III/IV endometriosis lesions. Indications for operation were endometriosis symptoms, sonographic findings and/or infertility.Methods: A total of 456 patients who underwent stage III/IV endometriosis surgery between 2004 and 2014 were sent a questionnaire relating to their postoperative medical treatment, pregnancies, relief of symptoms and recurrence. Responses of 206 patients (45.2%) and their clinical data were analysed for this study.Results: A total of 66.5% (N = 137) of patients had stage III disease, and 33.5% (N = 69) had stage IV disease. The average age was 37 years (17-59). A total of 63.1% (N = 130) of surgeries were performed by laparoscopy, 21.8% (N = 45) were performed by laparotomy and 15% (N = 31) were performed by conversion. Complete resection of endometriosis lesions was achieved in 90.8% of patients (N = 187). After surgery, 48.5% (N = 100) of the women did not receive hormonal treatment; the main reason was the desire for children in 53%. Complete or partial relief in complaints was achieved in 93.2% (N = 192). The rate of recurrence was 21.8% (N = 45). The statistically significant factors that was associated with a higher risk to develop recurrence was an age < 35 (p < 0.005). After surgery, 65.8% (79/120) of patients who wished to have children became pregnant. There was a statistically significant association among a higher postoperative pregnancy rate and age < 35 (p < 0.003) in multivariate logistic regression analysis and laparoscopic surgical access in univariate logistic regression analysis (p < 0.01).Conclusion: We assessed the high percentage of complete or partial relief of symptoms of 93.2%, the high postoperative pregnancy rate of 65.8% and the low rate of recurrence of 21.8% compared to international literature to be very encouraging for women suffering from moderate and severe endometriosis. Though laparoscopy is considered the 'gold standard'of endometriosis surgery, laparotomy still may be indicated in patients with extensive endometriosis especially to preserve reproductive function. [ABSTRACT FROM AUTHOR]

MEMS-based piezoelectric energy harvesters utilize the principle of piezoelectricity for harvesting energy from the ambient vibrations of the environment. These energy harvesters are popular because of their small size. Most of these energy harvesters are constructed using a cantilever beam or plate structure comprising of single or multiple beam or plates. This paper presents the idea of coupling effect present in the piezoelectric multiple-plate cantilever structures. In these multi-plate structures, the fixed ends of plates are connected by a metal layer. We observe that the vibrations of one plate tend to affect the vibrations and output of the neighboring plate. In this paper, we present a qualitative explanation of this coupling effect among the neighboring plates in terms of their electrical and mechanical interaction. Then we present a Finite Element Method Analysis of these multi-plate cantilever structures on COMSOL Multiphysics platform to verify our proposed hypothesis of coupling effect occurring in these structures. [ABSTRACT FROM AUTHOR]

TNT, accidentally released at several manufacturing sites, contaminates ground water and soil. It has a toxic effect to algae and invertebrate, and chronic exposure to TNT also causes harmful effects to human. On the other hand, many plants including Arabidopsis thaliana have the ability to metabolize TNT either completely or at least to a reduced less toxic form. In A. thaliana, the enzyme UDP glucosyltransferase (UDPGT) can further conjugate the reduced forms 2-HADNT and 4-HADNT (2-hydroxylamino-4, 6- dinitrotoluene and 4-hydroxylamino-2, 6- dinitrotoluene) of TNT. Based on the experimental analysis, existing literature and phylogenetic analysis, it is evident that among 107 UDPGT proteins only six are involved in the TNT degrading process. A total of 13 UDPGT proteins including five of these TNT degrading proteins fall within the same group of phylogeny. Thus, these 13 UDPGT proteins have been classified into two groups, TNT-degrading and TNT-non-degrading proteins. To understand the differences in TNT-degrading capacities; using homology modeling we first predicted two structures, taking one representative sequence from both the groups. Next, we performed molecular docking of the modeled structure and TNT reduced form 2-hydroxylamino-4, 6- dinitrotoluene (2-HADNT). We observed that while the Trp residue located within the active site region of the TNT- degrading protein showed π-Cation interaction; such type of interaction was absent in TNT-non-degrading protein, as the respective Trp residue lay outside of the pocket in this case. We observed the conservation of this π-Cation interaction during MD simulation of TNT-degrading protein. Thus, the position and the orientation of the active site residue Trp could explain the presence and absence of TNT-degrading capacity of the UDPGT proteins. [ABSTRACT FROM AUTHOR]

Objective: Surgeon-controlled endoscope leading assistance systems are a novelty in endoscopic surgery. These systems were evaluated for their applicability and reliability in operative gynecology. In this regard, we evaluated possible methods of operation, operative time, setup time, and comfort for the surgeon, complications, blood transfusions, length of stay, hemoglobin levels, and demographic data. Methods: Two systems with technically identical camera control systems were applied, the SOLOASSIST™ system and the Einstein Vision™ 3D system. The arm systems are attached to the operating table and controlled by surgeon via a manual control, a remote control or a foot switch. Comfort for the surgeon was evaluated using a questionnaire (scale 1-5; 1 'very good', 5 'poor'). All data were collected prospectively in a database (IBM SPSS Statistics 20) and evaluated. Results: One hundred and four patients underwent surgery supported by an active control system. In 43 (41 %) cases, oncological interventions were performed. Average setup time was 7 (3-30) min. There was a significant learning curve regarding the mounting of the system after 20 operations ( p = 0.045). Overall comfort was rated as 'good', divided into control 2.2 (2-4), physical effort 2.1 (1-4), picture quality 1.6 (1-3), and overall satisfaction 2.1 (1-4). About 75 unwanted camera movements were noticed in 104 surgeries. Complications occurred in no case (0 %). Conclusion: The application of an active camera control system was evaluated to be safe for all gynecological laparoscopies. Picture blur is avoided even during prolonged complex procedures. Moreover, the assistant is able to support the surgeon with two instruments, with the result that the presence of a second assistant is not required for complex interventions. Causing only minimal setup time, the examined active control systems improve the effectiveness of surgeries. The physical effort required for the assistant decreases and, by reducing tiring operations and tremor, subsequently, higher precision is reached. [ABSTRACT FROM AUTHOR]

Interactions between distantly placed amino acids in the primary chain (long-range) play a very crucial role in the formation and stabilization of the tertiary structure of a protein, while interactions between closely placed amino acids in the primary chain (short-range) mostly stabilize the secondary structures. Every protein needs to maintain marginal stability in order to perform its physiological functions in its native environment. The requirements for this stability in mesophilic and thermophilic proteins are different. Thermophilic proteins need to form more interactions as well as more stable interactions to survive in the extreme environment, they live in. Here, we aim to find out how the interacting amino acids in three-dimensional space are positioned in the primary chains in thermophilic and mesophilic. How does this arrangement help thermophiles to maintain their structural integrity at high temperatures? Working on a dataset of 1560 orthologous pairs we perceive that thermophiles are not only enriched with long-range interactions, they feature bigger connected clusters and higher network densities compared to their mesophilic orthologs, at higher interaction strengths between the amino acids. Moreover, we have observed the enrichment of different types of interactions at different secondary structural regions., Competing Interests: Declaration of Competing Interest The authors declare that no competing interests exist., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Metabolism is the key cellular process of plant physiology. Understanding metabolism and its dynamical behavior under different conditions may help plant biotechnologists to design new cultivars with desired goals. Computational systems biochemistry and incorporation of different omics data unravelled active metabolism and its variations in plants. In this review, we mainly focus on the basics of flux balance analysis (FBA), elementary flux mode analysis (EFMA), and some advanced computational tools. We describe some important results that were obtained using these tools. Limitations and challenges are also discussed.

Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) is the most common cancer among men in India, and is associated with poor prognosis and frequent recurrence. Cellular heterogeneity in OSCC-GB was investigated by single-cell RNA sequencing of tumors derived from the oral cavity of 12 OSCC-GB patients, 3 of whom had concomitant presence of a precancerous lesion (oral submucous fibrosis [OSMF]). Unique malignant cell types, features, and phenotypic shifts in the stromal cell population were identified in oral tumors with associated submucous fibrosis. Expression levels of FOS, ATP1A, and DUSP1 provided robust discrimination between tumors with or without the concomitant presence of OSMF. Malignant cell populations shared between tumors with and without OSMF were enriched with the expression of partial epithelial-mesenchymal transition (pEMT) or fetal cell type signatures indicative of two dominant cellular programs in OSCC-GB-pEMT and fetal cellular reprogramming. Malignant cells exhibiting fetal cellular and pEMT programs were enriched with the expression of immune-related pathway genes known to be involved in antitumor immune response. In the tumor microenvironment, higher infiltration of immune cells than the stromal cells was observed. The T cell population was large in tumors and diverse subtypes of T cells with varying levels of infiltration were found. We also detected double-negative PLCG2 + T cells and cells with intermediate M1-M2 macrophage polarization. Our findings shed light on unique aspects of cellular heterogeneity and cell states in OSCC-GB., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Quercetin (Qu), a potential bioflavonoid has gained considerable interest as a promising chemotherapeutic drug which can inhibit the proliferation of triple-negative breast cancer (TNBC) cells due to its regulation of the expression of tumor-suppressor gene metastasis and antioxidant property. Notably, Qu exhibits a very negligible cytotoxic effect on normal cells, even with high-dose treatment, while it is shows high affinity to TNBC. However, the efficiency of Qu is limited clinically due to its poor bioavailability, caused by its low aqueous solubility (2.15 μg mL -1 at 25 °C), rapid gastrointestinal digestion and chemical instability in alkaline and neutral media. Herein, polydopamine (PDA)-coated, NH 2 -PEG-NH 2 and hyaluronic acid (HA)-functionalized Gd 3+ -doped Prussian blue nanocubes (GPBNC) are reported as a multifunctional platform for the codelivery of Qu as a chemotherapeutic agent and GPBNC as a photodynamic (PDT) and photothermal (PTT) agent with improved therapeutic efficiency to overcome theses barriers. PDA, NH 2 -PEG-NH 2 and HA stabilize GPBNC@Qu and facilitate bioavailability and active-targeting, while absorption of near infrared (NIR) (808 nm; 1 W cm -2 ) induces PDT and PTT activities and dual T 1 - T 2 -weighted magnetic resonance imaging (MRI) with high relaxometric parameters ( r 1 10.06 mM -1 s -1 and r 2 24.96 mM -1 s -1 at a magnetic field of 3 T). The designed platform shows a pH-responsive Qu release profile and NIR-induced therapeutic efficiency of ∼79% in 20 minutes of irradiation, wherein N-terminal gardermin D (N-GSDMD) and a P2X7-receptor-mediated pyroptosis pathway induces cell death, corroborating the up-regulation of NLRP3, caspase-1, caspase-5, N-GSDMD, IL-1β, cleaved Pannexin-1 and P2X7 proteins. More interestingly, the increasing relaxivity values of Prussian blue nanocubes with Gd 3+ doping have been explained on the basis of Solomon-Bloembergen-Morgan theory, considering inner- and outer-sphere relaxivity, wherein crystal defects, coordinated water molecules, tumbling rate, metal to water proton distance, correlation time, magnetisation value etc. play a significant role. In summary, our study suggests that GPBNC could be a beneficial nanocarrier for theranostic purposes against TNBC, while our conceptual study clearly demonstrates the role of various factors in increasing relaxometric parameters.

Proteins from thermophilic organisms are a matter of immense interest for decades because of its application in fields like de-novo protein design, thermostable variants of biocatalysts etc. Previous studies have found several sequence and structural adaptations related to thermal stability, while charge reversal study remains ignored. Here we address whether charge reversal mutations naturally occur in mesophilic-thermophilic/hyperthermophilic orthologous proteins. Do they contribute to thermal stability? Our systematic study on 1550 mesophilic-thermophilic/hyperthermophilic orthologous protein pairs with remarkable structural and topological similarity, shows gain in coulombic interaction energy in thermophilic/hyperthermophilic proteins at short range associated with partially exposed and buried charge reversal mutations, which may enhance thermostability. Our findings call forth its application in future protein engineering studies. Communicated by Ramaswamy H. Sarma.

Carbon dots (CQDs) have been widely investigated as prime candidates for developing a tumor theranostic platform due to their tunable fluorescence emission and excitation, high water solubility, good photostability, and biocompatibility. Among the CQDs, natural CQDs are an emerging class of nanomaterials in the carbon family. Herein, highly fluorescent carbon quantum dots (CQDs) were synthesized from orange juice using a one-step hydrothermal method and characterized by different techniques. After that, CQD/Ag heterostructures were synthesized by the reduction of silver salt, in particular silver nitrate (AgNO 3 ) solution using sodium borohydride (NaBH 4 ) in different ratios. The photostability and characterization of CQD/Ag heterostructures were investigated. At last, a comparative cellular toxicity measurement was done to select the superior CQD/Ag heterostructure in the human colorectal carcinoma (HCT 116) cell line along with the imaging property. The detailed cell death signaling was also observed in the HCT 116 cell line via the ROS-dependent mitochondrial-mediated pathway, where Akt (RAC-α serine/threonine-protein kinase) played a important role., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

A targeted multimodal strategy on a single nanoplatform is attractive in the field of nanotheranostics for the complete ablation of cancer. Herein, we have designed mesoporous silica ( m -SiO 2 )-coated Prussian blue nanocubes (PBNCs), functionalized with hyaluronic acid (HA) to construct a multifunctional PBNC@ m -SiO 2 @HA nanoplatform that exhibited good biocompatibility, excellent photodynamic activity, and in vitro T 1 -weighted magnetic resonance imaging ability ( r 1 ∼ 3.91 mM -1 s -1 ). After loading doxorubicin into the as-prepared PBNC@ m -SiO 2 @HA, the developed PBNC@ m -SiO 2 @HA@DOX displayed excellent pH-responsive drug release characteristics. Upon irradiation with 808 nm (1.0 W cm -2 ) laser light, PBNC@ m -SiO 2 @HA@DOX exhibited synergistic photodynamic and chemotherapeutic efficacy (∼78% in 20 minutes) for human colorectal carcinoma (HCT 116) cell line compared to solo photodynamic or chemotherapy. Herein, the chemo-photodynamic therapeutic process was found to follow the apoptotic pathway via ROS-mediated mitochondrion-dependent DNA damage with a very low cellular uptake of PBNC@ m -SiO 2 @HA@DOX for the human embryonic kidney (HEK 293) cell line, illustrating its safety. Hence, it may be stated that the developed nanoplatform can be a potential theranostic agent for future applications. Most interestingly, we have noted variation in r 1 at each step of the functionalization along with size variation that has been the first time modelled on the basis of the Solomon-Bloembergen-Morgan theory considering changes in the defect crystal structure, correlation time, water diffusion rate, etc. , due to varied interactions between PBNC and water molecules., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Klebsiella pneumoniae is a leading cause of pneumonia and septicemia across the world. The rapid emergence of multidrug-resistant K. pneumoniae strains necessitates the discovery of effective drugs against this notorious pathogen. However, there is a dearth of knowledge on the mechanisms by which this deadly pathogen subverts host cellular machinery. To fill this knowledge gap, our study attempts to identify the potential mechanisms of host cell subversion by building a K. pneumoniae -human interactome based on rigorous computational methodology. The putative host targets inferred from the predicted interactome were found to be functionally enriched in the host's immune surveillance system and allied functions like apoptosis, hypoxia, etc. A multifunctionality-based scoring system revealed P53 as the most multifunctional protein among host targets accompanied by HIF1A and STAT1. Moreover, mining of host protein-protein interaction (PPI) network revealed that host targets interact among themselves to form a network (TTPPI), where P53 and CDC5L occupy a central position. The TTPPI is composed of several inter complex interactions which indicate that K. pneumoniae might disrupt functional coordination between these protein complexes through targeting of P53 and CDC5L. Furthermore, we identified four pivotal K. pneumoniae- targeted transcription factors (TTFs) that are part of TTPPI and are involved in generating host's transcriptional response to K. pneumoniae- mediated sepsis. In a nutshell, our study identifies some of the pivotal molecular targets of K. pneumoniae which primarily correlate to the physiological response of host during K. pneumoniae- mediated sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saha and Kundu.)

Monitoring frameworks under a non-disaster scenario can be helpful to identify the various socio-technical constraints of local and regional origin which influence the economics and resources management of marine fisheries. However, local-scale manifestations of regional/global changes due to the rapid onset of a disaster scenario may lead to unprecedented distortion of the market demand-supply value chains for the fisheries sector at shorter temporal scales. The global pandemic of COronaVIrus Disease (COVID-19) provided a unique short, temporal window to study the evolution of socio-economic challenges to sustainable fishing in the Bay of Bengal (BoB), India. The present study provides a detailed multi-source assessment of the factors that lead to massive complications of market disruption beginning with a public curfew on 22nd March 2020, followed by a nationwide complete lockdown of 54 days beginning from 25th March 2020, indicating an "all-pain no-gain" scenario for the fishers. Aggravating factors as a cessation of food services, and the restriction of exports of perishable commodities indicated negative spin-offs for allied activities sectors such as food processing due to low or negligible demand. The present investigation also indicated that as part of rehabilitation, policies related to overfishing are necessary to promote sustainable fishing practices in the BoB region in a post-pandemic period. New policy frameworks must consider the community-centric factors which facilitated the alleviation of the impacts of anthropogenic activities related to fishing and the slow restoration of the demand-supply chain, with long-term benefits for natural resources sustenance and to aid marine conservation efforts., (© 2021 The Authors.)

Background: Growing evidences suggest that microRNAs (miRNAs) can efficiently regulate gene expression at intracellular and extracellular levels. It has been previously reported that plant/food-derived miRNAs are highly enriched in human serum or serum from phytophagous animals, and they are responsible for regulating mammalian gene expression. Thus, miRNAs could function as active signaling molecules, which carry information across distinct species or even kingdoms. However, the mode of miRNA shuttling among various organisms is still a mystery to unravel. The intra and inter kingdom miRNA transfer has boosted up the hypothesis about the potential impact of plant or animal miRNAs on each other. To our knowledge, the software for analyzing cross-kingdom miRNA-targets is lacking., Results: We have developed a web-tool "IIKmTA: Inter and Intra Kingdom miRNA-Target Analyzer" utilizing a database; the data of which have been collected from another web server. Here, user can analyze the targeting potential of (i) plant miRNAs on animal UTRs (Untranslated regions), and vice versa (i.e., inter kingdom), (ii) plant miRNAs on plant UTRs and animal miRNAs on animal UTRs (i.e., intra kingdom). Further, user can analyze (i) miRNAs to targets, (ii) targets to miRNAs, and (iii) miRNA sets targeting sets of targets. For a wide variety of animal and plant species, IIKmTA can identify the miRNA binding sites in the probable target UTRs. Moreover, GC% and AU% of miRNAs will be calculated. All the results can be saved as .csv file., Conclusions: Recent researches identified miRNAs in plants and human secretions and their role in regulating the human genes. Such findings indicate the therapeutic role of secretory miRNAs of such plants which exhibits medicinal value and in near future many diseases may be treated by consumption of these plant miRNAs through food. Using our newly developed database and analyzing tool, one can easily determine the different relationships between miRNAs and their targets across kingdoms. IIKmTA is freely available at http://www.bioinformatics.org/iikmta/ .

Introduction: For the last two decades, obesity rates have been increasing in both developed and developing countries, with the number of obese women roughly doubling during this period (Stevens et al. in Popul Health Metr 10(1):33, 2012). Obesity represents one of the biggest epidemics of the 21st century. The aim of this retrospective study is to characterise the outcomes of gynaecologic surgeries in cases of extremely obese women with a body mass index (BMI) over 40 kg/m 2 ., Methods: This study is a retrospective case control study in a single-centre setting. Our clinical database was searched for gynaecological operations performed on morbidly obese patients (BMI > 40 kg/m 2 ) between 2009 and 2014 in the Department of Gynaecology and Obstetrics at Hannover Medical School. We matched these results with random patients of normal body weight who had similar surgical procedures and diseases., Results: We included 97 obese patients in our case group and 99 patients in the control group. We found an association between a strongly elevated BMI and peri- and postoperative morbidity. Both intraoperative and postoperative complications are significantly increased in morbid obesity with a BMI over > 40 kg/m 2 . We observed intraoperative complications in 55.6% and postoperative complications in 50.5% of patients with extreme obesity. In contrast, the complication rate in the control group with a normal BMI was 11% intraoperatively (p = 0.0001) and 3% postoperatively (p = 0.0001). The data showed that perioperative and postoperative morbidity could be reduced by laparoscopic surgery in many cases, with a significant lower rate of difficulties with closing the wound, a significant shorter duration of surgery and a significant lower rate of infections combined with a significant lower reoperation rate and shorter hospital stay. In gynaecological-oncological diseases, we could demonstrate a reduced radicality during the operative procedure due to extreme obesity., Discussion: Dealing with the growing number of obese patients is essential, because the problems emerging from obesity are manifold for the treating hospitals as well as the general health system. For this high-risk patient group, it is indispensable to obtain a thorough overview of the patient's overall situation preoperatively to ensure good perioperative care and complications management.

Objectives: Myomas are defined as benign tumours that arise from smooth muscle cells of the uterus. Clinically, they are found in 5-77% of women of reproductive age. The prevalence rate varies considerably in the literature and a large number of fibroids do not cause symptoms. The lifetime risk of acquiring myomas is 70% for Caucasian women and ≥ 80% for African American women., Materials/methods: The data of 265 patients undergoing surgery for symptomatic myomas by laparoscopy or laparotomy, performed in the gynaecological department of Hannover Medical School, Hannover, Germany, between 2009 and 2013, were retrospectively analysed in this retrospective design study., Results: High pregnancy rates (up to 70%) and birth rates (up to 86%) after myomectomy, regardless of the surgical approach adopted, were found in the current study. The trend was that ≥ 3 myomas and those that were ≥ 6 cm in size were almost always removed by laparotomy in our clinic. It was possible to remove up to 42 myomas without having to perform a hysterectomy. A statistically significant negative correlation was observed in relation to the association between the size of the largest myoma extracted and the pregnancy rate (p = 0.02). A statistically significant correlation between the number of removed myomas and the pregnancy rate was observed for patients who wished to bear children (p = 0.010). Elevated complication rates (of up to 50%) were reported for more than three extracted myomas with a statistically significance (p = 0.0471)., Conclusions: It is necessary to ensure sound preoperative selection of the surgical approach in order to achieve the most optimal results, especially for those patients who wished to bear children.

Purpose: Laparoscopy is nowadays a well-established surgical method and plays a main role in an ever-increasing range of indications in gynaecology. High-quality studies of surgical techniques are necessary to improve the quality of patient care. The present study aims at evaluating postoperative pain after gynaecological laparoscopy depending on the intraoperative CO 2 pressure., Methods: In a prospective, monocentric, randomized single-blind study at the Department of Gynaecology and Obstetrics at the Hannover Medical School, we include patients scheduled for different laparoscopic procedures. Randomization of the intraoperative CO 2 pressure was carried out in six groups. Pain was assessed the day after surgery by the blinded nurse using a visual analogue scale., Results: 550 patients were included in the period from May 2013 to January 2016. The analysis of the per protocol population PPP (n = 360) showed no statistically significant difference between the six intervention groups with regard to mean postoperative pain perception. In direct comparison between two groups, an intraoperative CO 2 pressure of 15 mmHg was associated with a significant higher pain score than a pressure of 12 mmHg. The difference was 7.46 mm on a 10 cm VAS., Conclusions: The results of our study indicate that a CO 2 pressure of 12 versus 15 mmHg can be advantageous. However, the clinical relevance remains unclear due to the low difference in pain. The additional benefit of an even lower pressure of 10 or 8 mmHg cannot be reliably assessed; we found signs of poor visibility conditions in these low pressure groups.

Background and Purpose: The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT)., Patients and Methods: Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis., Results: LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5)., Conclusion: Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters.

Chlorophyll is one of the most important pigments present in green plants and rice is one of the major food crops consumed worldwide. We curated the existing genome scale metabolic model (GSM) of rice leaf by incorporating new compartment, reactions and transporters. We used this modified GSM to elucidate how the chlorophyll is synthesized in a leaf through a series of bio-chemical reactions spanned over different organelles using inorganic macronutrients and light energy. We predicted the essential reactions and the associated genes of chlorophyll synthesis and validated against the existing experimental evidences. Further, ammonia is known to be the preferred source of nitrogen in rice paddy fields. The ammonia entering into the plant is assimilated in the root and leaf. The focus of the present work is centered on rice leaf metabolism. We studied the relative importance of ammonia transporters through the chloroplast and the cytosol and their interlink with other intracellular transporters. Ammonia assimilation in the leaves takes place by the enzyme glutamine synthetase (GS) which is present in the cytosol (GS1) and chloroplast (GS2). Our results provided possible explanation why GS2 mutants show normal growth under minimum photorespiration and appear chlorotic when exposed to air.

Due to socio-economic reasons, it is essential to design efficient stress-tolerant, more nutritious, high yielding rice varieties. A systematic understanding of the rice cellular metabolism is essential for this purpose. Here, we analyse a genome-scale metabolic model of rice leaf using Flux Balance Analysis to investigate whether it has potential metabolic flexibility to increase the biosynthesis of any of the biomass components. We initially simulate the metabolic responses under an objective to maximize the biomass components. Using the estimated maximum value of biomass synthesis as a constraint, we further simulate the metabolic responses optimizing the cellular economy. Depending on the physiological conditions of a cell, the transport capacities of intracellular transporters (ICTs) can vary. To mimic this physiological state, we randomly vary the ICTs' transport capacities and investigate their effects. The results show that the rice leaf has the potential to increase glycine and starch in a wide range depending on the ICTs' transport capacities. The predicted biosynthesis pathways vary slightly at the two different optimization conditions. With the constraint of biomass composition, the cell also has the metabolic plasticity to fix a wide range of carbon-nitrogen ratio.

We describe the construction and analysis of a genome-scale metabolic model representing a developing leaf cell of rice (Oryza sativa) primarily derived from the annotations in the RiceCyc database. We used flux balance analysis to determine that the model represents a network capable of producing biomass precursors (amino acids, nucleotides, lipid, starch, cellulose, and lignin) in experimentally reported proportions, using carbon dioxide as the sole carbon source. We then repeated the analysis over a range of photon flux values to examine responses in the solutions. The resulting flux distributions show that (1) redox shuttles between the chloroplast, cytosol, and mitochondrion may play a significant role at low light levels, (2) photorespiration can act to dissipate excess energy at high light levels, and (3) the role of mitochondrial metabolism is likely to vary considerably according to the balance between energy demand and availability. It is notable that these organelle interactions, consistent with many experimental observations, arise solely as a result of the need for mass and energy balancing without any explicit assumptions concerning kinetic or other regulatory mechanisms.

Background: The three-dimensional structure of a protein can be described as a graph where nodes represent residues and the strength of non-covalent interactions between them are edges. These protein contact networks can be separated into long and short-range interactions networks depending on the positions of amino acids in primary structure. Long-range interactions play a distinct role in determining the tertiary structure of a protein while short-range interactions could largely contribute to the secondary structure formations. In addition, physico chemical properties and the linear arrangement of amino acids of the primary structure of a protein determines its three dimensional structure. Here, we present an extensive analysis of protein contact subnetworks based on the London van der Waals interactions of amino acids at different length scales. We further subdivided those networks in hydrophobic, hydrophilic and charged residues networks and have tried to correlate their influence in the overall topology and organization of a protein., Results: The largest connected component (LCC) of long (LRN)-, short (SRN)- and all-range (ARN) networks within proteins exhibit a transition behaviour when plotted against different interaction strengths of edges among amino acid nodes. While short-range networks having chain like structures exhibit highly cooperative transition; long- and all-range networks, which are more similar to each other, have non-chain like structures and show less cooperativity. Further, the hydrophobic residues subnetworks in long- and all-range networks have similar transition behaviours with all residues all-range networks, but the hydrophilic and charged residues networks don't. While the nature of transitions of LCC's sizes is same in SRNs for thermophiles and mesophiles, there exists a clear difference in LRNs. The presence of larger size of interconnected long-range interactions in thermophiles than mesophiles, even at higher interaction strength between amino acids, give extra stability to the tertiary structure of the thermophiles. All the subnetworks at different length scales (ARNs, LRNs and SRNs) show assortativity mixing property of their participating amino acids. While there exists a significant higher percentage of hydrophobic subclusters over others in ARNs and LRNs; we do not find the assortative mixing behaviour of any the subclusters in SRNs. The clustering coefficient of hydrophobic subclusters in long-range network is the highest among types of subnetworks. There exist highly cliquish hydrophobic nodes followed by charged nodes in LRNs and ARNs; on the other hand, we observe the highest dominance of charged residues cliques in short-range networks. Studies on the perimeter of the cliques also show higher occurrences of hydrophobic and charged residues' cliques., Conclusions: The simple framework of protein contact networks and their subnetworks based on London van der Waals force is able to capture several known properties of protein structure as well as can unravel several new features. The thermophiles do not only have the higher number of long-range interactions; they also have larger cluster of connected residues at higher interaction strengths among amino acids, than their mesophilic counterparts. It can reestablish the significant role of long-range hydrophobic clusters in protein folding and stabilization; at the same time, it shed light on the higher communication ability of hydrophobic subnetworks over the others. The results give an indication of the controlling role of hydrophobic subclusters in determining protein's folding rate. The occurrences of higher perimeters of hydrophobic and charged cliques imply the role of charged residues as well as hydrophobic residues in stabilizing the distant part of primary structure of a protein through London van der Waals interaction.