bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteoarticular Infections in Children: Accurately Distinguishing between MSSA and Kingella kingae
Authors: Coulin Benoit , DeMarco Giacomo , Vazquez Oscar , Spyropoulou Vasiliki , Gavira Nathaly , Vendeuvre Tanguy , Tabard-Fougère Anne , Dayer Romain , Steiger Christina , Ceroni Dimitri
Published: December 2022

Introduction: Osteoarticular infections (OAIs) constitute serious paediatric conditions that may cause severe complications. Identifying the causative organism is one of the mainstays of the care process, since its detection will confirm the diagnosis, enable adjustments to antibiotic therapy and thus optimize outcomes. Two bacteria account for the majority of OAIs before 16 years of age: Staphylococcus aureus is known for affecting the older child, whereas Kingella kingae affects infants and children younger than 4 years old. We aimed to better define clinical characteristic and biological criteria for prompt diagnosis and discrimination between these two OAI. Materials and methods: We retrospectively studied 335 children, gathering 100 K. kingae and 116 S. aureus bacteriologically proven OAIs. Age, gender, temperature at admission, involved bone or joint, and laboratory data including bacterial cultures were collected for analysis. Comparisons between patients with OAI due to K. kingae and those with OAI due to S. aureus were performed using the Mann–Whitney and Kruskal–Wallis tests. Six cut-off discrimination criteria (age, admission’s T°, WBC, CRP, ESR and platelet count) were defined, and their respective ability to differentiate between OAI patients due to K. kingae versus those with S. aureus was assessed by nonparametric receiver operating characteristic (ROC) curves. Results: Univariate analysis demonstrated significant differences between the two populations for age of patients, temperature at admission, CRP, ESR, WBC, and platelet count. AUC assessed by ROC curves demonstrated an exquisite ability to discriminate between the two populations for age of the patients; whereas AUC for CRP (0.79), temperature at admission (0.76), and platelet count (0.76) indicated a fair accuracy to discriminate between the two populations. Accuracy to discriminate between the two subgroups of patients was considered as poor for WBC (AUC = 0.62), and failed for ESR (AUC = 0.58). On the basis of our results, the best model to predict K. kingae OAI included of the following cut-offs for each parameter: age < 43 months, temperature at admission < 37.9 °C, CRP < 32.5 mg/L, and platelet count > 361,500/mm3. Conclusions: OAI caused by K. kingae affects primarily infants and toddlers aged less than 4 years, whereas most of the children with OAI due to MSSA were aged 4 years and more. Considering our experience on the ground, only three variables were very suggestive of an OAI caused by K. kingae, i.e., age of less than 4 years, platelet count > 400,000, and a CRP level below 32.5 mg/L, whereas WBC and ESR were relatively of limited use in clinical practice.
Gluten Degradation by the Gut Microbiota of Ulcerative Colitis Patients
Authors: Harringer Emma Olivia Schultz , Durack Juliana , Piceno Yvette , Andersen Vibeke , Lynch Susan V.
Published: December 2022

Several studies have reported improved disease symptomatology in ulcerative colitis (UC) patients consuming a gluten free diet. This observation coupled with diversity depletion in the gut microbiota of UC patients led us to hypothesize that UC-associated enteric microbes differentially metabolize dietary gluten to produce immunogenic products that promote inflammation. Gluten concentration in stool was determined using gluten-specific ELISA, and gluten intake was assessed by food frequency questionnaire (FFQ) in UC (n = 12) and healthy controls (HC; n = 13). Gluten-metabolizing bacteria were isolated on minimal media supplemented with 1% gluten from UC and HC and identified by 16S rRNA profiling. Cell-free culture media from gluten metabolizing gut bacterial isolates was assessed for immunogenicity in vitro using HT29 colonocytes. Compared to HC, UC patients did not consume gluten differently (Mann–Whitney; p > 0.10) and exhibited equivalent levels of gluten in their feces (Mann–Whitney; p = 0.163). The profile of gluten-degrading bacteria isolated from UC stool was distinct (Chi-square; p ≤ 0.0001). Compared with Enterococcus isolates, products of gluten degradation by Bacillus strains induced higher IL8 and lower occludin (Mann–Whitney; p = 0.002 and p = 0.059, respectively) gene expression in colonocytes irrespective of whether they originated from UC or healthy gut. Members of HC and UC microbiota exhibit gluten-degrading ability, metabolites of which influence genes involved in inflammation and barrier function in enteric colonocyte cultures. Preliminary findings of this study warrant further investigations into the mechanisms by which gut microbiota contribute to UC pathogenesis through gluten degradation.
Modulatory Mechanisms of Pathogenicity in Porphyromonas gingivalis and Other Periodontal Pathobionts
Authors: Sharaf Sara , Hijazi Karolin
Published: December 2022

The pathogenesis of periodontitis depends on a sustained feedback loop where bacterial virulence factors and immune responses both contribute to inflammation and tissue degradation. Periodontitis is a multifactorial disease that is associated with a pathogenic shift in the oral microbiome. Within this shift, low-abundance Gram-negative anaerobic pathobionts transition from harmless colonisers of the subgingival environment to a virulent state that drives evasion and subversion of innate and adaptive immune responses. This, in turn, drives the progression of inflammatory disease and the destruction of tooth-supporting structures. From an evolutionary perspective, bacteria have developed this phenotypic plasticity in order to respond and adapt to environmental stimuli or external stressors. This review summarises the available knowledge of genetic, transcriptional, and post-translational mechanisms which mediate the commensal-pathogen transition of periodontal bacteria. The review will focus primarily on Porphyromonas gingivalis.
Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance
Authors: Choudhary M. Iqbal , Römling Ute , Nadeem Faiza , Bilal Hafiz Muhammad , Zafar Munirah , Jahan Humera , ur-Rahman Atta
Published: December 2022

Antimicrobial resistance and tolerance are natural phenomena that arose due to evolutionary adaptation of microorganisms against various xenobiotic agents. These adaptation mechanisms make the current treatment options challenging as it is increasingly difficult to treat a broad range of infections, associated biofilm formation, intracellular and host adapted microbes, as well as persister cells and microbes in protected niches. Therefore, novel strategies are needed to identify the most promising drug targets to overcome the existing hurdles in the treatment of infectious diseases. Furthermore, discovery of novel drug candidates is also much needed, as few novel antimicrobial drugs have been introduced in the last two decades. In this review, we focus on the strategies that may help in the development of innovative small molecules which can interfere with microbial resistance mechanisms. We also highlight the recent advances in optimization of growth media which mimic host conditions and genome scale molecular analyses of microbial response against antimicrobial agents. Furthermore, we discuss the identification of antibiofilm molecules and their mechanisms of action in the light of the distinct physiology and metabolism of biofilm cells. This review thus provides the most recent advances in host mimicking growth media for effective drug discovery and development of antimicrobial and antibiofilm agents.
Effect of Parthenium hysterophorus L. Invasion on Soil Microbial Communities in the Yellow River Delta, China
Authors: Shang Shuai , Zhang Zaiwang , Zhao Liping , Liu Longxiang , Shi Dongli , Xu Hui , Zhang Hanjie , Xie Wenjun , Zhao Fengjuan , Zhou Zhihao , Xu Jikun , Wang Jun
Published: December 2022

Parthenium hysterophorus L., as an invasive plant, has negatively impacted the ecosystem functioning and stability of the terrestrial ecosystem in China. However, little information was available for its effects on microorganisms in the Yellow River Delta (YRD), the biggest newly-formed wetland in China. In the present study, high-throughput sequencing technology was used to obtain the bacterial community in soils and roots of different plant species, including P. hysterophorus and some native ones in the YRD. Our results showed that the Proteobacteria, Acidobacteriota, Gemmatimonadota, and Actinobacteriota were dominant in the rhizosphere soils of P. hysterophorus (84.2%) and Setaria viridis (86.47%), and the bulk soils (80.7%). The Proteobacteria and Actinobacteriota were dominant within the root of P. hysterophorus. A total of 2468 bacterial OTUs were obtained from different groups among which 140 were observed in all the groups; 1019 OTUs were shared by P. hysterophorus non-rhizosphere soil bacteria (YNR) P. hysterophorus rhizosphere soil bacteria (YRR) groups. The indexes of the ACE (823.1), Chao1 (823.19), Simpson (0.9971), and Shannon (9.068) were the highest in the YRR groups, showing the greatest bacterial community diversity. Random forest analysis showed that the Methylomirabilota and Dadabacteria (at the phylum level) and the Sphingomonas, and Woeseia (at the genus level) were identified as the main predictors among different groups. The LEfSe results also showed the essential role of the Acidobacteriota in the YRR group. The SourceTracker analysis of the bacterial community of the YRR group was mainly from GBS groups (average 53.14%) and a small part was from YNR groups (average 6.56%), indicating that the P. hysterophorus invasion had a more significant effect on native plants’ rhizosphere microorganisms than soil microorganisms. Our observations could provide valuable information for understanding the bacterial diversity and structure of the soil to the invasion of P. hysterophorus.
Diagnostic Performance of Competitive ELISA and Western Blot Methods for the Detection of Antibodies against Theileria equi and Babesia caballi
Authors: Yang Guangpu , Zhou Bingqian , Chen Kewei , Hu Zhe , Guo Wei , Wang Xiaojun , Du Cheng
Published: December 2022

Theileria equi (T. equi) and Babesia caballi (B. caballi) are the causative pathogens of Equine piroplasmosis (EP), a disease that has brought huge economic losses and great restrictions to the global equine industry. Rapid and accurate diagnostic methods are critical for the effective monitoring of the disease. In this study, we developed novel competitive ELISA methods and western blot assays based on the EMA1 or Bc48 proteins to detect antibodies against T. equi or B. caballi, respectively. In the novel cELISA, horseradish peroxidase (HRP)-labeled monoclonal antibodies are used in place of enzyme-conjugated secondary antibodies, in order to speed up the entire procedure. These methods have high sensitivity and no cross-reactivity with antibodies against other equine diseases. In the newly developed western blot assays, we optimized the dilution of T. equi or B. caballi positive serum samples to 1:200. Compared with the commercially available kit, both the novel cELISA assay and the western blot assay showed high coincidence rates in detecting antibodies against T. equi and B. caballi. Taken together, the novel cELISA and the western blot assays for detecting antibodies against T. equi or B. caballi have the potential to rapidly test for T. equi or B. caballi and to contribute to the surveillance and control of this disease.
Neobaicalein Inhibits Th17 Cell Differentiation Resulting in Recovery of Th17/Treg Ratio through Blocking STAT3 Signaling Activation
Authors: Chen Jian-Yu , Yang Ying-Jie , Ma Xue-Qin , Cao Qi , Wei Shan-Shan , Pan Rong-Rong , Nan Li-Hong , Liu Yao-Jun , Cao Yan , Tian Xiao-Yun , Deng Shan , Cheng Zai-Xing , Wang Can-Jian , Chen Tao , Zheng Yan-Fang , Huang Ming-Qing
Published: December 2022

Huangqin is the dried root of Scutellaria baicalensis Georgi, which has been widely utilized for heat-clearing (Qingre) and dewetting (Zaoshi), heat-killed (Xiehuo) and detoxifying (Jiedu) in the concept of Traditional Chinese Medicine and is used for treating inflammation and cancer in clinical formulas. Neobaicalein (NEO) is of flavonoid isolated from Huangqin and has been reported to possess prominent anti-inflammatory effects in published work. Th17/Treg balance shift to Th17 cells is an essential reason for autoimmune inflammatory diseases. However, the role NEO plays in Th17 and Treg and the underlying mechanism has not been elucidated yet. Network pharmacology-based study revealed that NEO predominantly regulated IL-17 signaling pathway. Moreover, our result shown that NEO (3–30 μmol/L) down-regulated Th17 differentiation and cellular supernatant and intracellular IL-17A level and tumor necrosis factor α production in a concentration-dependent manner. The further mechanism research revealed that NEO also specifically inhibited phosphorylation of STAT3(Tyr725) and STAT4 (Y693) without influence on activation of STAT5 and STAT6 in splenocytes. Immunofluorescence results illuminated that NEO effectively blocked STAT3 translocated into nucleus. Interestingly, NEO at appreciated dose could only inhibit Th17 cell differentiation and have no effect on Treg differentiation. The present study revealed that NEO effectively inhibited Th17 cell differentiation through specifically blocking the activation of STAT3 signaling without inactivation of STAT5 and STAT6. Additional inhibitory effect on activation of STAT4 by NEO also suggested the potential for antagonism against Th1 differentiation. All work suggested that NEO may be a potential candidate for immunoregulation and treating autoimmune inflammatory diseases through inhibiting immune cell viability and T cell differentiation.
Melanin Synthesis Inhibition Activity of Compounds Isolated from Bamboo Shoot Skin (Phyllostachys pubescens)
Authors: Ashour Ahmed , Elbermawi Ahmed , Amen Yhiya , Allam Ahmed E. , Ikeda Hiromi , Nagata Maki , Kumagae Kenta , Azuma Tomoyo , Taguchi Aya , Takemoto Takuya , Matsumoto Masako , Shimizu Kuniyoshi
Published: December 2022

This study targets the evaluation of melanin synthesis inhibition activity of the bamboo shoot skin as agro-waste. The total methanolic extract of bamboo peel extract was evaluated for its skin protective effects via measuring its melanin inhibitory activity and its suppression activity on the expression of tyrosinase mRNA levels. Results showed that bamboo peel extract has a good ability for the inhibition of melanin synthesis so further studies were performed for the isolation of its constituents. Twelve compounds have been isolated from the shoot skin of Phyllostachys pubescens. Their structures were elucidated based on extensive spectroscopic methods. The melanin inhibition potential of the isolates was tested with their collagen-production-promoting activity for the determination of active principles. Results showed that Betulinic acid, tachioside, and 1,2-dilinolenin significantly suppressed melanin production per cell compared to control. Triacontanol, tricin, and (+)-lyoniresinol 9′-O-glucoside also tended to decrease melanin production per cell. These findings indicated that the skin of bamboo shoots, a significant agricultural waste, is a useful natural source for further research on its potential for aging problems such hyperpigmentation and cognitive function impairment.
Phytochemical Characterization, Antioxidant and Anti-Inflammatory Effects of Cleome arabica L. Fruits Extract against Formalin Induced Chronic Inflammation in Female Wistar Rat: Biochemical, Histological, and In Silico Studies
Authors: Allagui Ikram , Horchani Mabrouk , Zammel Nourhene , Jalouli Maroua , Elfeki Abdelfatteh , Kallel Choumous , Mansour Lamjed , Alwasel Salah , Harrath Abdel Halim , Jannet Hichem Ben , Salah Allagui Mohamed , Hcini Kheiria
Published: December 2022

In recent decades, the use of herbs and plants has been of great interest, as they have been the sources of natural products, commonly named as bioactive compounds. In specific, the natural compounds from the Capparaceae family which has been proved to have antioxidant, anti-inflammatory, antimicrobial and anti-carcinogenic activities, by several studies. Cleome arabica L. (CA) specie is the most used medicinal plants in Tunisia and elsewhere in North African countries for treatment of various diseases including diabetes, rheumatism, inflammation, cancer, and digestive disorders. The current work was undertaken to estimate the total phenolic, flavonoid and condensed tannin contents, to identify and quantify the polyphenolic compounds, and to evaluate the antioxidant and the anti-inflammatory proprieties of CA fruits extract against formalin induced chronic inflammation in Female Wistar rats. In fact, the antioxidant activity was tested by Diphenyl-1-Picrylhydrazyl free radical scavenging (DPPH), Ferric reducing antioxidant power (FRAP) and Nitric Oxide radical (NO·). Anti-inflammatory effect of fruits extract was examined using formalin (2%) induced paw edema in rats. Molecular docking tools were used to investigate the interaction of some compounds from CA fruits extract with the cyclooxygenase-2 (COX-2) target protein. Our results showed that, the total phenolic, flavonoid and tannins contents, which were assessed by the Folin-Ciocalteu, Quercetin, and Catechin methods, respectively, were 230.22 mg gallic acid equivalent/g dry weight (mg GAE/g DW), 55.08 mg quercetin equivalent/g dry weight (QE/g DW) and 15.17 mg catechin equivalents/g dry weight (CatE/g DW), respectively. HPLC analysis revealed the presence of five polyphenolic compounds whose catechin was found to be the most abundant compounds. The antioxidant activity of extract was quantified by DPPH, FRAP and NO· tests and IC50 reached the values of 3.346 mg/mL, 2.306 and 0.023 mg/mL, respectively. Cleome fruits ameliorated the histological integrity of the skin and alleviated the disruptions in hematological parameters (WBC, LYM, RBC, and HGB), inflammatory cytokines (IL-1β, IL-6, TNF-α), C-reactive protein, and some oxidative stress markers (TBARS (−49%) and AOPP (−42%) levels, SOD (+33%) and GPx (+75%) activities, and GSH (+49%) content) induced by formalin injection. Moreover, the in-silico investigation had shown that CA fruits extract compounds have a stronger interaction with COX-2 active site, more than the reference drug “indomethacin” (two H-bonds). Our research gives pharmacological backing to the healthcare utilization of Cleome plant in the treatment of inflammatory diseases and oxidative harm.
Copolymers of 4-Trimethylsilyl Diphenyl Acetylene and 1-Trimethylsilyl-1-Propyne: Polymer Synthesis and Luminescent Property Adjustment
Authors: Shen Tanxiao , Chen Manyu , Zhang Haoke , Sun Jing Zhi , Tang Ben Zhong
Published: December 2022

Poly(4-trimethylsilyl diphenyl acetylene) (PTMSDPA) has strong fluorescence emission, but its application is limited by the effect of aggregation-caused quenching (ACQ). Copolymerization is a commonly used method to adjust the properties of polymers. Through the copolymerization of 4-trimethylsilyl diphenyl acetylene and 1-trimethylsilyl-1-propyne (TMSP), we successfully realized the conversion of PTMSDPA from ACQ to aggregation-induced emission (AIE) and aggregation-induced emission enhancement (AEE). By controlling the monomer feeding ratio and with the increase of the content of TMSDPA inserted into the copolymer, the emission peak was red-shifted, and a series of copolymers of poly(TMSDPA-co-TMSP) that emit blue–purple to orange–red light was obtained, and the feasibility of the application in explosive detection was verified. With picric acid (PA) as a model explosive, a super-quenching process has been observed, and the quenching constant (KSV) calculated from the Stern–Volmer equation is 24,000 M−1, which means that the polymer is potentially used for explosive detection.
Centranthus ruber (L.) DC. and Tropaeolum majus L.: Phytochemical Profile, In Vitro Anti-Denaturation Effects and Lipase Inhibitory Activity of Two Ornamental Plants Traditionally Used as Herbal Remedies
Authors: Musolino Vincenzo , Marrelli Mariangela , Perri Maria Rosaria , Palermo Martina , Gliozzi Micaela , Mollace Vincenzo , Conforti Filomena
Published: December 2022

Ornamental plants often gain relevance not only for their decorative use, but also as a source of phytochemicals with interesting healing properties. Herein, spontaneous Centranthus ruber (L.) DC. and Tropaeolum majus L., mainly used as ornamental species but also traditionally consumed and used in popular medicine, were investigated. The aerial parts were extracted with methanol trough maceration, and resultant crude extracts were partitioned using solvents with increasing polarity. As previous studies mostly dealt with the phenolic content of these species, the phytochemical investigation mainly focused on nonpolar constituents, detected with GC-MS. The total phenolic and flavonoid content was also verified, and HPTLC analyses were performed. In order to explore the potential antiarthritic and anti-obesity properties, extracts and their fractions were evaluated for their anti-denaturation effects, with the use of the BSA assay, and for their ability to inhibit pancreatic lipase. The antioxidant properties and the inhibitory activity on the NO production were verified, as well. Almost all the extracts and fractions demonstrated good inhibitory effects on NO production. The n-hexane and dichloromethane fractions from T. majus, as well as the n-hexane fraction from C. ruber, were effective in protecting the protein from heat-induced denaturation (IC50 = 154.0 ± 1.9, 270.8 ± 2.3 and 450.1 ± 15.5 μg/mL, respectively). The dichloromethane fractions from both raw extracts were also effective in inhibiting pancreatic lipase, with IC50 values equal to 2.23 ± 0.02 mg/mL (for C. ruber sample), and 2.05 ± 0.02 mg/mL (T. majus). Obtained results support the traditional use of these species for their beneficial health properties and suggest that investigated plant species could be potential sources of novel antiarthritic and anti-obesity agents.
Biological Activity of Amidino-Substituted Imidazo [4,5-b]pyridines
Authors: Pavlinac Ida Boček , Zlatić Katarina , Persoons Leentje , Daelemans Dirk , Banjanac Mihajlo , Radovanović Vedrana , Butković Kristina , Kralj Marijeta , Hranjec Marijana
Published: December 2022

A series of cyano- and amidino-substituted imidazo[4,5-b]pyridines were synthesized using standard methods of organic synthesis, and their biological activity was evaluated. Biological evaluation included in vitro assessment of antiproliferative effects on a diverse selection of human cancer cell lines, antibacterial activity against chosen Gram-positive and Gram-negative bacterial strains, and antiviral activity on a broad panel of DNA and RNA viruses. The most pronounced antiproliferative activity was observed for compound 10, which contained an unsubstituted amidino group, and compound 14, which contained a 2-imidazolinyl amidino group; both displayed selective and strong activity in sub-micromolar inhibitory concentration range against colon carcinoma (IC50 0.4 and 0.7 μM, respectively). All tested compounds lacked antibacterial activity, with the exception of compound 14, which showed moderate activity against E. coli (MIC 32 μM). Bromo-substituted derivative 7, which contained an unsubstituted phenyl ring (EC50 21 μM), and para-cyano-substituted derivative 17 (EC50 58 μM) showed selective but moderate activity against respiratory syncytial virus (RSV).
Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core
Authors: Ţînţaş Mihaela-Liliana , Peauger Ludovic , Alix Florent , Papamicaël Cyril , Besson Thierry , Sopková-de Oliveira Santos Jana , Gembus Vincent , Levacher Vincent
Published: December 2022

The DYRK (Dual-specificity tyrosine phosphorylation-regulated kinase) family of protein kinases is involved in the pathogenesis of several neurodegenerative diseases. Among them, the DYRK1A protein kinase is thought to be implicated in Alzheimer’s disease (AD) and Down syndrome, and as such, has emerged as an appealing therapeutic target. DYRKs are a subset of the CMGC (CDK, MAPKK, GSK3 and CLK) group of kinases. Within this group of kinases, the CDC2-like kinases (CLKs), such as CLK1, are closely related to DYRKs and have also sparked great interest as potential therapeutic targets for AD. Based on inhibitors previously described in the literature (namely TG003 and INDY), we report in this work a new class of dihydroquinolines exhibiting inhibitory activities in the nanomolar range on hDYRK1A and hCLK1. Moreover, there is overwhelming evidence that oxidative stress plays an important role in AD. Pleasingly, the most potent dual kinase inhibitor 1p exhibited antioxidant and radical scavenging properties. Finally, drug-likeness and molecular docking studies of this new class of DYRK1A/CLK1 inhibitors are also discussed in this article.
Docking and Molecular Dynamic Investigations of Phenylspirodrimanes as Cannabinoid Receptor-2 Agonists
Authors: Omar Abdelsattar M. , Aljahdali Anfal S. , Safo Martin K. , Mohamed Gamal A. , Ibrahim Sabrin R. M.
Published: December 2022

Cannabinoid receptor ligands are renowned as being therapeutically crucial for treating diverse health disorders. Phenylspirodrimanes are meroterpenoids with unique and varied structural scaffolds, which are mainly reported from the Stachybotrys genus and display an array of bioactivities. In this work, 114 phenylspirodrimanes reported from Stachybotrys chartarum were screened for their CB2 agonistic potential using docking and molecular dynamic simulation studies. Compound 56 revealed the highest docking score (−11.222 kcal/mol) compared to E3R_6KPF (native agonist, gscore value −12.12 kcal/mol). The molecular docking and molecular simulation results suggest that compound 56 binds to the putative binding site in the CB2 receptor with good affinity involving key interacting amino acid residues similar to that of the native ligands, E3R. The molecular interactions displayed π–π stacking with Phe183 and hydrogen bond interactions with Thr114, Leu182, and Ser285. These findings identified the structural features of these metabolites that might lead to the design of selective novel ligands for CB2 receptors. Additionally, phenylspirodrimanes should be further investigated for their potential as a CB2 ligand.
Sulfonamides with Heterocyclic Periphery as Antiviral Agents
Authors: Moskalik Mikhail Yu.
Published: December 2022

Sulfonamides are the basic motifs for a whole generation of drugs from a large group of antibiotics. Currently, research in the field of the new sulfonamide synthesis has received a “second wind”, due to the increase in the synthetic capabilities of organic chemistry and the study of their medical and biological properties of a wide spectrum of biological activity. New reagents and new reactions make it possible to significantly increase the number of compounds with a sulfonamide fragment in combination with other important pharmacophore groups, such as, for example, a wide class of N-containing heterocycles. The result of these synthetic possibilities is the extension of the activity spectrum—along with antibacterial activity, many of them exhibit other types of biological activity. Antiviral activity is also observed in a wide range of sulfonamide derivatives. This review provides examples of the synthesis of sulfonamide compounds with antiviral properties that can be used to develop drugs against coxsackievirus B, enteroviruses, encephalomyocarditis viruses, adenoviruses, human parainfluenza viruses, Ebola virus, Marburg virus, SARS-CoV-2, HIV and others. Since over the past three years, viral infections have become a special problem for public health throughout the world, the development of new broad-spectrum antiviral drugs is an extremely important task for synthetic organic and medicinal chemistry. Sulfonamides can be both sources of nitrogen for building a nitrogen-containing heterocyclic core and the side chain substituents of a biologically active substance. The formation of the sulfonamide group is often achieved by the reaction of the N-nucleophilic center in the substrate molecule with the corresponding sulfonylchloride. Another approach involves the use of sulfonamides as the reagents for building a nitrogen-containing framework.
ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications
Authors: Chen Xin-yu , Dai Ying-hong , Wan Xin-xing , Hu Xi-min , Zhao Wen-juan , Ban Xiao-xia , Wan Hao , Huang Kun , Zhang Qi , Xiong Kun
Published: December 2022

Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. Recently, ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. Recent studies have also reported that ZBP1 induces necroptosis in non-viral infections and mediates necrotic signal transduction by a unique mechanism. This review highlights the discovery of ZBP1 and its novel findings in necroptosis and provides an insight into its critical role in the crosstalk between different types of cell death, which may represent a new therapeutic option.
Vitamin E Intake and Risk of Prostate Cancer: A Meta-Analysis
Authors: Loh Wei Qi , Youn Jiyoung , Seow Wei Jie
Published: December 2022

Vitamin E is a group of antioxidative tocopherols and tocotrienols that play a potential role in chemoprevention. Studies investigating the association between vitamin E and prostate cancer risk have been conflicting. We identified observational and interventional studies examining the association between vitamin E intake and prostate cancer risk from PubMed, EMBASE and the Cochrane Library. A random-effects model was used to perform a meta-analysis and estimate relative risks (RRs) and the corresponding 95% confidence intervals (CIs) of prostate cancer risk according to vitamin E intake. Subgroup analyses were conducted by study design, sample size, study population characteristics, geographical region, and dose of vitamin E intake. The association between dietary (RR = 0.97; 95% CI = 0.92–1.02) and supplemental (RR = 0.99; 95% CI = 0.94–1.04) vitamin E intake on prostate cancer risk was non-significant. In subgroup analyses, supplemental vitamin E was significantly associated with reduced prostate cancer risk in studies in Europe (RR = 0.81, 95% CI = 0.69–0.97). Overall, this meta-analysis demonstrates little evidence for a beneficial effect of vitamin E intake on prostate cancer risk but suggests that there may be some conditions in which supplements could confer a protective effect on prostate cancer risk.
RAGE-Dependent Effect of Exogenous Methylglyoxal Intake on Lung Biomechanics in Mice
Authors: Al-Robaiy Samiya , Navarrete Santos Alexander , Simm Andreas
Published: December 2022

Methylglyoxal (MG) is a known highly reactive dicarbonyl and precursor to free radicals and advanced glycation end-products (AGEs). It is discussed to be involved in tissue aging and in the pathogenesis of different degenerative diseases. The effect of long-term oral administration of MG, simulating dietary MG intake, on the lung biomechanics of wild type (WT) and receptor for advanced glycation end-products knockout (RAGE-KO) mice was studied using an ex vivo ventilation system starting at the age of 6 months and after feeding for 6 and 12 months with MG. Our results showed that MG was taken up in the circulation and efficiently excreted with urine. The amount of free urinary MG measured after 12 months of feeding was lowered. After 12 months feeding, a significant airway resistance increase accompanied by a decrease of the maximal inspiratory airflow was observed in WT animals. No effect of MG in lung function of RAGE-KO mice could be detected. Despite the evidence that MG entered the systemic circulation, no MG-derived AGE accumulation was detected in the lung lysates in dependency on MG-feeding. Our data indicate that the short-term feeding of MG has little effect in vivo. Only after long-term treatment was MG secretion reduced, leading to tissue impairment.
Whole Genome Sequencing and Comparative Genomics of Indian Isolates of Wheat Spot Blotch Pathogen Bipolaris sorokiniana Reveals Expansion of Pathogenicity Gene Clusters
Authors: Yadav Sagar , Raazi Zarrine , Shivaraj Sheelavanta Matha , Somani Deepika , Prashant Ramya , Kulkarni Abhijeet , Kumar Rajeev , Biradar Suma , Desai Shreenivas , Kadoo Narendra
Published: December 2022

Spot blotch is a highly destructive disease in wheat caused by the fungal pathogen Bipolaris sorokiniana (teleomorph, Cochliobolus sativus). It is prevalent in warm and humid areas, including Africa, Asia, Latin America, and the USA. In the present study, twelve isolates of B. sorokiniana were collected from wheat fields in three different geographical locations in India. The pathogenicity of seven sporulating isolates was assessed on ‘DDK 1025’, a spot blotch-susceptible wheat variety under greenhouse conditions. The isolate ‘D2’ illustrated the highest virulence, followed by ‘SI’ and ‘BS52’. These three isolates were sequenced using the Illumina HiSeq1000 platform. The estimated genome sizes of the isolates BS52, D2, and SI were 35.19 MB, 39.32 MB, and 32.76 MB, with GC contents of 48.48%, 50.43%, and 49.42%, respectively. The numbers of pathogenicity genes identified in BS52, D2, and SI isolates were 2015, 2476, and 2018, respectively. Notably, the isolate D2 exhibited a relatively larger genome with expanded arsenals of Biosynthetic Gene Clusters (BGCs), CAZymes, secretome, and pathogenicity genes, which could have contributed to its higher virulence among the tested isolates. This study provides the first comparative genome analysis of the Indian isolates of B. sorokiniana using whole genome sequencing.
The Biocontrol Potential of Endophytic Trichoderma Fungi Isolated from Hungarian Grapevines, Part II, Grapevine Stimulation
Authors: Csótó András , Kovács Csilla , Pál Károly , Nagy Antal , Peles Ferenc , Fekete Erzsébet , Karaffa Levente , Kubicek Christian P. , Sándor Erzsébet
Published: December 2022

In the first part of this two-piece publication, the isolation, identification and in vitro characterization of ten endophytic Trichoderma isolates were reported. Here we report the ability of two different mixes of some of these isolates (Trichoderma simmonsii, Trichoderma orientale and Trichoderma gamsii as well as of Trichoderma afroharzianum and T. simmonsii) to colonize and stimulate the growth of grapevines. Two commercial vineyards about 400 km away from the site of isolation were used as experimental fields, from which the strains of three Trichoderma species were re-isolated up to four years after rootstock soaking treatment with conidiospores, performed before planting. The treatments decreased the overall percentage of lost plants of about 30%, although a low number of lost plants (about 5%) were observed also in the control plot. For all cultivars and clones, the Trichoderma treatments significantly increased both the bud burst ratio and bud burst vigor index. In addition, the grape must parameters such as the Brix degrees, as well as the extract, the D-glucose and the D-fructose concentrations all appeared to be improved, suggesting a potentially higher ethanol content of the produced wine. We conclude that grapevine-endophytic Trichoderma isolates promote plant growth, which could be a useful feature for sustainable agriculture in general and integrated plant production in particular.
Indirect Evidence Based on Mating-Type Ratios for the Role of Sexual Reproduction in European and Chinese Populations of Plenodomus biglobosus (Blackleg of Oilseed Rape)
Authors: King Kevin M. , Canning Gail , Zhou Kang , Liu Zekuan , Wu Mingde , West Jonathan S.
Published: December 2022

Blackleg (Phoma) disease, caused by the ascomycete fungi Plenodomus biglobosus and P. lingam, threatens oilseed rape (OSR; Brassica napus) crops internationally. In many parts of the world, both species co-occur, but in China only P. biglobosus has so far been reported. Plenodomus biglobosus reproduces asexually (pycnidiospores), but also sexually (pseudothecia-yielding ascospores), via a heterothallic mating system requiring MAT1-1 and MAT1-2 genotypes. However, the roles of airborne ascospore inoculum in driving blackleg disease outbreaks in China are less well understood compared to elsewhere in the world. This is despite the very different agronomic cropping practices in parts of China, in which paddy rice and OSR are often grown in rotation; OSR stubble is often submerged under water for long periods potentially affecting pseudothecial development. Here, we indirectly investigate the potential role of sexual reproduction by developing new polymerase chain reaction (PCR) -based mating-type diagnostics for P. biglobosus and subsequently screening an international collection of 59 European and 157 Chinese isolates. Overall, in both Europe and China, P. biglobosus mating types did not deviate from a 1:1 ratio, such as is generally thought to occur under frequency-dependent selection in sexually reproducing pathogen populations. Both mating types were balanced in all the individual European countries tested (Austria, France, Poland, UK). Conversely, in China, mating types were only balanced in the eastern region; in the northern and southwestern regions there were skewed ratios, more typical of predominantly asexual reproduction, towards MAT1-1 and MAT1-2, respectively. The implications of these findings and future research directions for improved understanding of P. biglobosus epidemiology on OSR, particularly in China, are considered.
Characterisation of Streptococcus suis Isolates in the Czech Republic Collected from Diseased Pigs in the Years 2018–2022
Authors: Zouharová Monika , Šimek Bronislav , Gebauer Jan , Králová Natálie , Kucharovičová Ivana , Plodková Hana , Pecka Tomáš , Brychta Marek , Švejdová Marie , Nedbalcová Kateřina , Matiašková Katarína , Matiašovic Ján
Published: December 2022

As in other countries, in the Czech Republic, Streptococcus suis infection in pigs is considered an economically significant disease for the pig industry, though little is known about its population structure. We collected S. suis isolates from 144 farms in the years 2018–2022. All samples were taken from animals suffering from symptoms indicating possible S. suis infection. Serotyping revealed the presence of 23 different serotypes, and 18.94% were non-typable strains. The most common was S7 (14.96%), while other serotypes had frequencies of less than 10%. Sequence typing identified 56 different sequence types, including 31 newly assigned sequence types together with 41 new alleles in genes in the MLST schema. A large portion of isolates (25.70%) were of unknown sequence type. The most common sequence types were ST29 (14.77%) and ST28 (10.04%); the other sequence types had frequencies of less than 10%. In total, 100 different combinations of serotypes and sequence types were identified. Among them, S7ST29 was found in 72 isolates, representing 13.63% of all isolates, and was significantly associated with the central nervous system. Many other isolates of particular serotype and sequence type combinations were found in a few cases, and a number of isolates were non-typable.
A Simplified Multiplex PCR Assay for Simultaneous Detection of Six Viruses Infecting Diverse Chilli Species in India and Its Application in Field Diagnosis
Authors: Devi Oinam Priyoda , Sharma Susheel Kumar , Sanatombi Keithellakpam , Devi Konjengbam Sarda , Pathaw Neeta , Roy Subhra Saikat , Chanu Ngathem Taibangnganbi , Sanabam Rakesh , Devi Huirem Chandrajini , Singh Akoijam Ratankumar , Baranwal Virendra Kumar
Published: December 2022

Chilli is infected by at least 65 viruses globally, with a mixed infection of multiple viruses leading to severe losses being a common occurrence. A simple diagnostic procedure that can identify multiple viruses at once is required to track their spread, initiate management measures and manage them using virus-free planting supplies. The present study, for the first time, reports a simplified and robust multiplex PCR (mPCR) assay for the simultaneous detection of five RNA viruses, capsicum chlorosis orthotospovirus (CaCV), chilli veinal mottle virus (ChiVMV), large cardamom chirke virus (LCCV), cucumber mosaic virus (CMV), and pepper mild mottle virus (PMMoV), and a DNA virus, chilli leaf curl virus (ChiLCV) infecting chilli. The developed mPCR employed six pairs of primer from the conserved coat protein (CP) region of the respective viruses. Different parameters viz., primer concentration (150–450 nM) and annealing temperature (50 °C), were optimized in order to achieve specific and sensitive amplification of the target viruses in a single reaction tube. The detection limit of the mPCR assay was 5.00 pg/µL to simultaneously detect all the target viruses in a single reaction, indicating a sufficient sensitivity of the developed assay. The developed assay showed high specificity and showed no cross-amplification. The multiplex PCR assay was validated using field samples collected across Northeast India. Interestingly, out of 61 samples collected across the northeastern states, only 22 samples (36%) were positive for single virus infection while 33 samples (54%) were positive for three or more viruses tested in mPCR, showing the widespread occurrence of mixed infection under field conditions. To the best of our knowledge, this is the first report on the development and field validation of the mPCR assay for six chilli viruses and will have application in routine virus indexing and virus management.
Fabrication and Characterization of Pre-Defined Few-Layer Graphene
Authors: Wang Tingting , Jia Liangguang , Zhang Quanzhen , Xu Ziqiang , Huang Zeping , Yuan Peiwen , Hou Baofei , Song Xuan , Nie Kaiqi , Liu Chen , Wang Jiaou , Yang Huixia , Liu Liwei , Zhang Teng , Wang Yeliang
Published: December 2022

Graphene is one of the most well-known two-dimensional (2D) materials that has attracted significant interest due to its unique electrical and optical properties. Being a van der Waals substrate, the fabrication of few-layered graphene by stacking a pre-defined number of graphene monolayers is essential in the field. The thickness can influence the interface interaction and therefore tune the surface electronic properties. In the study, we demonstrate a bottom-up synthesis of pre-defined few-layer graphene on SiC substrate using the thermal decomposition method and carefully characterize its thickness by the non-damageable synchrotron-radiation-based X-ray photo-electron spectroscopy (SR-XPS). By varying the photon energy, we acquire different probe depths, resulting in the different intensity ratios of graphene to SiC substrate, which is then used to estimate the thickness of the few-layer graphene. Our calculation demonstrates that the thermal decomposition method in the study can repeatedly fabricate graphene samples with expected thickness. We further compare the obtained few-layer graphene to the single-layer graphene and HOPG using the scanning tunneling microscopy (STM) technique. Our work provides accurate methods for fabricating and characterizing pre-defined few-layer graphene, providing essential knowledge in future graphene-based thin film electronics.
Phenotypic Diversity in Pre- and Post-Attachment Resistance to Striga hermonthica in a Core Collection of Rice Germplasms
Authors: Samejima Hiroaki , Sugimoto Yukihiro
Published: December 2022

In sub-Saharan Africa, upland rice cultivation is expanding into rainfed areas endemic to the root parasitic weed Striga hermonthica. We evaluated the Striga resistance of 69 accessions from the World Rice Core Collection (WRC) to estimate the phenotypic diversity within the Oryza sativa species. Pre-attachment resistance was screened based on the germination-inducing activities of the root exudates, while post-attachment resistance was screened through rhizotron evaluation. The 69 WRC accessions showed a wide variation in both pre- and post-attachment resistance. Root exudates of one accession induced 0.04% germination, and those of some accessions displayed >80% germination. In the evaluation of post-attachment resistance, the successful parasitism percentages ranged from 1.3% to 60.7%. The results of these resistance evaluations were subjected to cluster analysis, which recognized five groups: group I of 27 accessions, with high pre- and post-attachment resistance; group II of 12 accessions, with high post-attachment resistance but moderate pre-attachment resistance; group III of 4 accessions, with low pre-attachment resistance; group IV of 13 accessions, with low post-attachment resistance; and group V of 13 accessions, with low pre- and post-attachment resistance. The wide variation found in the WRC accessions will help to elucidate the genetic factors underpinning pre- and post-attachment resistance.
The Effect of the Height of Coppicing and Harvest Season on the Yield and Quality of the Essential Oil of Kunzea ambigua
Authors: Park Chanjoo , Garland Sandra M. , Close Dugald C.
Published: December 2022

Kunzea ambigua is a small shrub belonging to the Myrtaceae family and the leaves are steam-distilled to produce a therapeutically active essential oil. With production moving from wild-harvested to orchardised stands, there is a need for harvest management of kunzea oil. This study compared the regrowth, essential oil content and composition of kunzea plants after harvesting vegetative material to a depth of 0.2 m above ground level (shallow-cut), relative to plants cut to a depth of 0.1 m above ground level (deep-cut) over the 2018/2019 growing season. Increased vegetative biomass accounted for the increased oil yield and was caused by consistently higher growth rates of 50 to 60% across all seasons in shallow-cut crops relative to those subject to deep-cut. Total soluble sugar concentrations were higher in the leaves and lower in the roots of deep-cut treated plants compared to the other treatments, indicating defoliated K. ambigua responds by mobilising sugars into above-ground biomass. The overall essential oil content of leaves was constant regardless of season, though the oil yield for shallow-cut was 1.9-fold higher at 11.79 ± 0.23 g/m2 compared to deep-cut (6.24 ± 0.18 g/m2). An interactive effect of harvest intensity with season was recorded for all major components except for a non-significant effect of season on terpinen-4-ol. Bicyclogermacrene and α-pinene were elevated in both shallow- and deep-cut treatments relative to control (un-cut) in spring, possibly due to the plant defense response after de-foliation. The highest percentage of bioactive compounds (1,8-cineole and viridiflorol) were present in autumn. Therefore, the recovery of biomass post-harvest is optimised by shallow-cut harvests, and the profile of kunzea oil can be manipulated to elevate levels of specific bioactive components by selecting to crop in autumn/spring.