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Hydroxysafflor yellow A (HSYA), an active ingredient extracted from Carthami flos, shows potential for treating ischemic stroke. This phase 1 study assessed the safety, tolerability, and pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers who received intravenous infusions of pure HSYA powder. The study comprised 2 parts. Part A was a randomized, double‐blind, placebo‐controlled dose‐escalation study that evaluated safety and tolerability. This included a single‐dose study with 7 dose levels of HSYA (6.25, 12.5, 25, 50, 75, 100, and 125 mg) in 52 volunteers, and a multidose study (100 and 125 mg) in 16 volunteers. Part B was an open‐label study where 12 volunteers received 75 mg of HSYA once daily for 14 consecutive days to examine PKs. There were no adverse events (AEs) leading to treatment discontinuation by HSYA throughout the treatment period. All reported AEs were mild and did not require special treatment. PK analysis revealed rapid absorption (median Tmax of 1.1 hours) and elimination (median t1/2 4.0 and 4.7 hours) of HSYA. Total body clearance on the 1st and 14th days was 1.7 and 1.6 L/h, respectively. [ABSTRACT FROM AUTHOR]

Brevibacillus brevis FJAT-0809-GLX has a broad spectrum of antimicrobial activity. Understanding the molecular basis of biocontrol ability of B. brevis will allow us to develop effective microbial agents for sustainable agriculture. In this study, we present the complete and annotated genome sequence of FJAT-0809-GLX. The complete genome size of B. brevis FJAT-0809-GLX was 6,137,019 bp, with 5688 predicted coding sequences (CDS). The average GC content of 47.38%, and there were 44 copies of the rRNAs operon (16S, 23S and 5S RNA), and 127 tRNA genes. A total of 11,162 genes were functionally annotated with the COG, GO, and KEGG databases, and 123 genes belonged to CAZymes. Genomic secondary metabolite analysis indicated 13 clusters encoding potential new antimicrobials. FJAT-0809-GLX was designated as B. brevis according to average nucleotide polymorphism (ANI) and phylogenetic analysis. The pangenome consisted of 7141 homologous genes, and 4469 homologous genes shared by B. brevis FJAT-0809-GLX, B. brevis NBRC100599, B. brevis DSM30, and B. brevis NCTC2611. The number of unique homologous genes of B. brevis FJAT-0809-GLX (419 genes) and B. brevis NBRC100599 (480 genes) were much more than those in B. brevis DSM30 (13 genes), and B. brevis NCTC2611 (6 genes). Nine gene clusters encoding for secondary metabolite biosynthesis were compared in the genome of B. brevis FJAT-0809-GLX with those of B. brevis NBRC100599, B. brevis DSM30 and B. brevis NCTC2611, and the gene clusters encoding for lantipeptide and transatpks-otherks only existed in genome of B. brevis FJAT-0809-GLX. The 11 BbPks genes were included in the B. brevis FJAT-0809-GLX genome, which contained the conserved PS-DH domain. The relative expression of BbPksL, BbPksM2, BbPksM3, BbPksN3, BbPksN4 and BbPksN5 reached a maximum at 120 h and then decreased at 144 h. Our results provided detailed genomic and Pks genes information for the FJAT-0809-GLX strain, and lid a foundation for studying its biocontrol mechanisms. [ABSTRACT FROM AUTHOR]

The utilization of an agricultural waste product known as palm kernel shells (PKS) combined with fine laterites (from basalt in Bangangté, West Cameroon) to produce low-cost and innovative materials with good bearing capacities for road pavement was investigated. Fine laterites from two soil profiles (BL31 and BL32) and made up of kaolinite, hematite, goethite, gibbsite, anatase, ilmenite and magnetite minerals were partially replaced with PKS at 15%, 25%, 35%, and 45% by weight. Physical and mechanical tests, including particle size distribution, Atterberg limits, unsoaked and soaked California Bearing Ratio (UCBR and SCBR), unconfined compressive strength (UCS), and tensile strength (Rt), were performed on the different mixtures. After the addition of PKS, a decrease in fine particle content (77 to 38%), liquidity limit (LL: 72 to 61%), plasticity index (PI: 30 to 19%), maximum dry density (MDD: 1.685 to 1.29 t/m3), and optimum moisture content (OMC: 27.5 to 24.0%) was noticed. Additionally, there was an increase in UCBR (16–72%), SCBR (14–66%), UCS (1.07–7.67 MPa), and Rt (2.24–9.71 MPa). This allows new materials suitable for the construction of base layers for low trafficked roads (T1–T2), as well as sub-base and base layers for high trafficked roads (T3), to be obtained. This newly formed material can be recommended locally for road construction works, though more in-depth studies are required. [ABSTRACT FROM AUTHOR]

ABSTRACTHuman colorectal cancers (CRCs) are readily colonized by colibactin-producing E. coli (CoPEC). CoPEC induces DNA double-strand breaks, DNA mutations, genomic instability, and cellular senescence. Infected cells produce a senescence-associated secretory phenotype (SASP), which is involved in the increase in tumorigenesis observed in CRC mouse models infected with CoPEC. This study investigated whether CoPEC, and the SASP derived from CoPEC-infected cells, impacted chemotherapeutic resistance. Human intestinal epithelial cells were infected with the CoPEC clinical 11G5 strain or with its isogenic mutant, which is unable to produce colibactin. Chemotherapeutic resistance was assessed in vitro and in a xenograft mouse model. Expressions of cancer stem cell (CSC) markers in infected cells were investigated. Data were validated using a CRC mouse model and human clinical samples. Both 11G5-infected cells, and uninfected cells incubated with the SASP produced by 11G5-infected cells exhibited an increased resistance to chemotherapeutic drugs in vitro and in vivo. This finding correlated with the induction of the epithelial to mesenchymal transition (EMT), which led to the emergence of cells exhibiting CSC features. They grew on ultra-low attachment plates, formed colonies in soft agar, and overexpressed several CSC markers (e.g. CD133, OCT-3/4, and NANOG). In agreement with these results, murine and human CRC biopsies colonized with CoPEC exhibited higher expression levels of OCT-3/4 and NANOG than biopsies devoid of CoPEC. Conclusion: CoPEC might aggravate CRCs by inducing the emergence of cancer stem cells that are highly resistant to chemotherapy.

Type II polyketide synthase (PKS) systems are a rich source of structurally diverse polycyclic aromatic compounds with clinically relevant antibiotic and chemotherapeutic properties. The enzymes responsible for synthesizing the polyketide core, known collectively as the minimal cassette, hold potential for applications in synthetic biology. The minimal cassette provides polyketides of different chain lengths, which interact with other enzymes that are responsible for the varied cyclization patterns. Additionally, the type II PKS enzyme clusters offer a wide repertoire of tailoring enzymes for oxidations, glycosylations, cyclizations, and rearrangements. This review begins with the variety of chemical space accessible with type II PKS systems including the recently discovered highly reducing variants that produce polyalkenes instead of the archetypical polyketide motif. The main discussion analyzes the previous approaches with an emphasis on further research that is needed to characterize the minimal cassette enzymes in vitro. Finally, the potential type II PKS systems hold the potential to offer new tools in biocatalysis and synthetic biology, particularly in the production of novel antibiotics and biofuels. [ABSTRACT FROM AUTHOR]

Piperazic acid is a cyclic nonproteinogenic amino acid that contains a hydrazine N-N bond formed by a piperazate synthase (KtzT-like). This amino acid, found in bioactive natural products synthesized by non-ribosomal peptide synthetases (NRPSs), confers conformational constraint to peptides, an important feature for their biological activities. Genome mining of Streptomyces strains has been revealed as a strategy to identify biosynthetic gene clusters (BGCs) for potentially active compounds. Moreover, the isolation of new strains from underexplored habitats or associated with other organisms has allowed to uncover new BGCs for unknown compounds. The in-house "Carlos Sialer (CS)" strain collection consists of seventy-one Streptomyces strains isolated from the cuticle of leaf-cutting ants of the tribe Attini. Genomes from twelve of these strains have been sequenced and mined using bioinformatics tools, highlighting their potential to encode secondary metabolites. In this work, we have screened in silico those genomes, using KtzT as a hook to identify BGCs encoding piperazic acid-containing compounds. This resulted in uncovering the new BGC dpn in Streptomyces sp. CS113, which encodes the biosynthesis of the hybrid polyketide–depsipeptide diperamycin. Analysis of the diperamycin polyketide synthase (PKS) and NRPS reveals their functional similarity to those from the aurantimycin A biosynthetic pathway. Experimental proof linking the dpn BGC to its encoded compound was achieved by determining the growth conditions for the expression of the cluster and by inactivating the NRPS encoding gene dpnS2 and the piperazate synthase gene dpnZ. The identity of diperamycin was confirmed by High-Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR) and by analysis of the domain composition of modules from the DpnP PKS and DpnS NRPS. The identification of the dpn BGC expands the number of BGCs that have been confirmed to encode the relatively scarcely represented BGCs for depsipeptides of the azinothricin family of compounds and will facilitate the generation of new-to-nature analogues by combinatorial biosynthesis. [ABSTRACT FROM AUTHOR]

The utilization of an agricultural waste product known as palm kernel shells (PKS) combined with fine laterites (from basalt in Bangangté, West Cameroon) to produce low-cost and innovative materials with good bearing capacities for road pavement was investigated. Fine laterites from two soil profiles (BL31 and BL32) and made up of kaolinite, hematite, goethite, gibbsite, anatase, ilmenite and magnetite minerals were partially replaced with PKS at 15%, 25%, 35%, and 45% by weight. Physical and mechanical tests, including particle size distribution, Atterberg limits, unsoaked and soaked California Bearing Ratio (UCBR and SCBR), unconfined compressive strength (UCS), and tensile strength (Rt), were performed on the different mixtures. After the addition of PKS, a decrease in fine particle content (77 to 38%), liquidity limit (LL: 72 to 61%), plasticity index (PI: 30 to 19%), maximum dry density (MDD: 1.685 to 1.29 t/m3), and optimum moisture content (OMC: 27.5 to 24.0%) was noticed. Additionally, there was an increase in UCBR (16–72%), SCBR (14–66%), UCS (1.07–7.67 MPa), and Rt (2.24–9.71 MPa). This allows new materials suitable for the construction of base layers for low trafficked roads (T1–T2), as well as sub-base and base layers for high trafficked roads (T3), to be obtained. This newly formed material can be recommended locally for road construction works, though more in-depth studies are required.

NAC is a class of plant-specific transcription factors that are widely involved in the growth, development and (a)biotic stress response of plants. However, their molecular evolution has not been extensively studied in Malvales, especially in Aquilaria sinensis, a commercial and horticultural crop that produces an aromatic resin named agarwood. In this study, 1502 members of the NAC gene family were identified from the genomes of nine species from Malvales and three model plants. The macroevolutionary analysis revealed that whole genome duplication (WGD) and dispersed duplication (DSD) have shaped the current architectural structure of NAC gene families in Malvales plants. Then, 111 NAC genes were systemically characterized in A. sinensis. The phylogenetic analysis suggests that NAC genes in A. sinensis can be classified into 16 known clusters and four new subfamilies, with each subfamily presenting similar gene structures and conserved motifs. RNA-seq analysis showed that AsNACs presents a broad transcriptional response to the agarwood inducer. The expression patterns of 15 AsNACs in A. sinensis after injury treatment indicated that AsNAC019 and AsNAC098 were positively correlated with the expression patterns of four polyketide synthase (PKS) genes. Additionally, AsNAC019 and AsNAC098 were also found to bind with the AsPKS07 promoter and activate its transcription. This comprehensive analysis provides valuable insights into the molecular evolution of the NAC gene family in Malvales plants and highlights the potential mechanisms of AsNACs for regulating secondary metabolite biosynthesis in A. sinensis, especially for the biosynthesis of 2-(2-phenyl) chromones in agarwood. [ABSTRACT FROM AUTHOR]

The growing global threat of antimicrobial resistance is reaching a crisis point as common bacterial infections, including those caused by pathogenic Neisseria species, are becoming increasingly untreatable. This is compelling the scientific community to search for new antimicrobial agents, taking advantage of computational mining and using whole genome sequences to discover natural products from the human microbiome with antibiotic effects. In this study, we investigated the crude extract from a Rothia dentocariosa strain with demonstrated antimicrobial activity against pathogenic Neisseria spp. by spot-on-lawn assay. The genomic DNA of the R. dentocariosa strain was sequenced, and bioinformatic evaluation was performed using antiSMASH and PRISM to search for biosynthetic gene clusters (BGCs). The crude extract with potential antimicrobial activity was run on Tricine-SDS-PAGE, and the putative peptides were characterised using liquid chromatography–tandem mass spectrometry (LC-MS). The crude extract inhibited the growth of the pathogenic Neisseria spp. Six BGCs were identified corresponding to non-ribosomal peptide synthases (NRPSs), polyketide synthases (PKSs), and ribosomally synthesised and post-translationally modified peptides. Three peptides were also identified corresponding to Actinorhodin polyketide putative beta-ketoacyl synthase 1. These findings serve as a useful reference to facilitate the research and development of NRPS and PKS as antimicrobial products against multidrug-resistant N. gonorrhoeae. [ABSTRACT FROM AUTHOR]

Given the pervasive influence of patriarchy in politics, women in the political arena must be equipped to address the various challenges that come with it. Therefore, there is a need for political education tailored to their specific needs. Women's political representation plays a vital role in advancing democracy. This study investigated political communication strategies and ideologies of Islamist parties in Indonesia, with a focus on enhancing female politicians' voters through political education. One of the Islamic parties in this research is the Prosperous Justice Party, also known as Partai Keadilan Sejahtera (PKS). The study employed a qualitative approach as the primary research method. The research suggests that Islamic parties can enhance their political communication strategies by integrating their political ideology. This political ideology can be transformed into guiding principles and spiritual development platforms that serve as a form of political education for political party cadres. This study highlights the challenges faced by those who may be reluctant to fully support women in politics. The strategy employed by PKS does not involve the abandonment of its core party ideology but rather focuses on reinforcing and promoting this ideology among its cadres and sympathizers through effective da'wah and cadre development. [ABSTRACT FROM AUTHOR]

Purpose: To report a rare type of Pallister-Killian syndrome (PKS) diagnosed prenatally by the utility of non-invasive prenatal testing (NIPT). Methods: NIPT was performed in the first trimester. Conventional karyotyping and chromosomal microarray analysis (CMA) were performed on the amniotic samples in the second trimester. Copy number variation sequencing (CNV-seq) was used for the validation of fetal skin and the placental tissue after pregnancy termination. Results: NIPT results showed increased signal from chromosome 12p. Subsequent prenatal diagnostic testing by karyotype revealed 47, XY, +i (12p), and CMA displayed four copies of 12p: 12p13.33-12p11.1(173786_34835641) × 4. The CNV-seq results of the fetal skin and the fetal side of placenta showed four copies of 12p13.33-p11 and an estimated chimeric duplication of 34.08 Mb (chimerism ratio: 10%) in 12 p13.33-p11, respectively. However, no abnormality was detected by CNV-seq at the maternal side of placenta. Conclusions: Our findings suggest that a positive signal from chromosome 12p on NIPT should raise suspicion for PKS. With the wide application of NIPT, the true positive of incidental finding is expected to increase. [ABSTRACT FROM AUTHOR]

Dinoflagellates are unicellular organisms that are implicated in harmful algal blooms (HABs) caused by potent toxins that are produced through polyketide synthase (PKS) pathways. However, the exact mechanisms of toxin synthesis are unknown due to a lack of genomic segregation of fat, toxins, and other PKS-based pathways. To better understand the underlying mechanisms, the actions and expression of the PKS proteins were investigated using the toxic dinoflagellate Amphidinium carterae as a model. Cerulenin, a known ketosynthase inhibitor, was shown to reduce acetate incorporation into all fat classes with the toxins amphidinol and sulpho-amphidinol. The mass spectrometry analysis of cerulenin-reacted synthetic peptides derived from ketosynthase domains of A. carterae multimodular PKS transcripts demonstrated a strong covalent bond that could be localized using collision-induced dissociation. One multi-modular PKS sequence present in all dinoflagellates surveyed to date was found to lack an AT domain in toxin-producing species, indicating trans-acting domains, and was shown by Western blotting to be post-transcriptionally processed. These results demonstrate how toxin synthesis in dinoflagellates can be differentiated from fat synthesis despite common underlying pathway. [ABSTRACT FROM AUTHOR]

Traditionally engineered to produce novel bioactive molecules, Type I modular polyketide synthases (PKSs) could be engineered as a new biosynthetic platform for the production of de novo fuels, commodity chemicals, and specialty chemicals. Previously, our investigations manipulated the first module of the lipomycin PKS to produce short chain ketones, 3-hydroxy acids, and saturated, branched carboxylic acids. Building upon this work, we have expanded to multi-modular systems by engineering the first two modules of lipomycin to generate unnatural polyketides as potential biofuels and specialty chemicals in Streptomyces albus. First, we produce 20.6 mg/L of the ethyl ketone, 4,6 dimethylheptanone through a reductive loop exchange in LipPKS1 and a ketoreductase knockouts in LipPKS2. We then show that an AT swap in LipPKS1 and a reductive loop exchange in LipPKS2 can produce the potential fragrance 3-isopropyl-6-methyltetrahydropyranone. Highlighting the challenge of maintaining product fidelity, in both bimodular systems we observed side products from premature hydrolysis in the engineered first module and stalled dehydration in reductive loop exchanges. Collectively, our work expands the biological design space and moves the field closer to the production of "designer" biomolecules.

Neglected invertebrates, marine flatworms, have attracted global research interest due to their biological and chemical potential properties. The marine flatworms (Turbellaria), Phylum Platyhelminthes, belong to the Polycladida group. There are about 3000 species of free-living flatworms that make a living by hunting and eating other animals. A marine flatworm Acanthozoon sp. was used in this study due to its abundant presence in the site location. Staphylococcus epidermidis is an opportunistic pathogenic bacterium that was previously considered a harmless skin disease bacterium. This species is now considered to be in the first rank among the causative agents of nosocomial infection, specifically in the form of infections of the urinary tract, respiratory tract, and surgical site wounds. The aims of this study were to explore the biological diversity of marine flatworm-associated bacteria with antipathogenic properties and to detect the presence of polyketide synthase (PKS) and nonribosomal peptide synthetase NRPS gene clusters through a molecular approach. Recent studies have shown that S. epidermidis undergoes functional changes in the pro-inflammatory peptide family so that it has functions in immune evasion and biofilm development. Therefore, the search for new antimicrobial compounds is urgently needed due to the limited choice of antibiotic use. In the preliminary screening by overlay test, 7 out of 17 (41.2%) isolates showed antibacterial activities. These isolates were reselected and their activity confirmed by using plug agar and disk-diffusion methods. The FA02, FA03, FA05, FA07, FA13, FA16, and FA17 isolates demonstrated their inhibitory activities consistently against the causative agent of nosocomial infection S. epidermidis. Based on the morphological and 16S rRNA partial sequencing analysis, these isolates were closely related to the genus Virgibacillus, Brevibacterium, Alcanivorax, and Vibrio. None of these seven antibacterial strains possesses PKS-I and PKS-II, except NRPS genes for Virgibacillus salarius strain FA02, V. salarius strain FA16, and V. salarius strain FA17. The results of this study showed that bacteria associated with marine flatworms have future potential as a source of promising natural products for the development of antibiotics.

Two Streptomyces strains, named N11-26 and DC10-5, were isolated from deep-sea and non-photosynthetic stony coral, respectively. Strain N11-26 produces lobophorin C and divergolides, which are antimicrobial substances. This study aimed to classify these strains and reveal their cryptic potential to synthesize other secondary metabolites, such as polyketides and nonribosomal peptides. Strains N11-26 and DC10-5 showed 16S rRNA gene sequence similarities of 100% and 99.9% to Streptomyces olivaceus NRRL B-3009T, respectively. By digital DNA–DNA hybridization using whole-genome sequences, these strains were classified as Streptomyces olivaceus. Strain N11-26 was closer to the type strain of S. olivaceus than strain DC10-5 and possessed 17 clusters of polyketide synthase (PKS) and/or nonribosomal peptide synthetases (NRPS) genes, whereas strain DC10-5 harbored 19 clusters. Putative products by these gene clusters were predicted by bioinformatic analyses. Although 15 clusters were conserved between the two strains, two and four clusters were specific in strains N11-26 and DC10-5, respectively. This represents a diversity of potential polyketide and nonribosomal peptide compounds between strains of S. olivaceus. To the best of our knowledge, this is the first report annotating all the PKS and NRPS gene clusters in S. olivaceus strains with their putative products to provide useful information for genome mining.

6-methylsalicylic acid (6-MSA) is a small, simple polyketide produced by a broad spectrum of fungal species. Since fungi obtained the ability to synthesize 6-MSA from bacteria through a horizontal gene transfer event, it has developed into a multipurpose metabolic hub from where numerous complex compounds are produced. The most relevant metabolite from a human perspective is the small lactone patulin as it is one of the most potent mycotoxins. Other important end products derived from 6-MSA include the small quinone epoxide terreic acid and the prenylated yanuthones. The most advanced modification of 6-MSA is observed in the aculin biosynthetic pathway, which is mediated by a non-ribosomal peptide synthase and a terpene cyclase. In this short review, we summarize for the first time all the possible pathways that takes their onset from 6-MSA and provide a synopsis of the responsible gene clusters and derive the resulting biosynthetic pathways. [ABSTRACT FROM AUTHOR]

Although e-Commerce is today's trading and shopping lifestyle, e-Commerce platforms are more used by buyers than sellers. This includes SME entrepreneurs who are seen to be lagging behind in taking advantage of this technology. SMEs are one of the economic segments that contribute the largest GDP for the country. In 2020, there will be a significant reduction in the contribution of SMEs to the country's GDP due to the closure of business and movement control orders. However, many SMEs are not trying to take advantage of this health and economic crisis to switch to online business, while this digital economy sector is the most booming economic segment during two years the country is in the pandemic era. Internet facilities are not optimally used by SMEs to explore new markets through business and digital marketing. This proves that SMEs behavioural acceptance is still low and not in line with Government aspirations. The successful implementation of intentions and actual behaviour is driven by positive attitudes, social support and a good behavioural control. By relying on the Model of Decomposed Theory of Planned Behaviour (DTPB) and empirical observations, this concept paper reviews the strengths of each determinant in more detail in order to predict the acceptance behaviour. The discussion found that the SMEs intention and actual behaviour towards e-Commerce usage are encourage by factor of attitude, subjective norms and perceived control behaviour which is based on beliefs of perceived usefulness, perceived ease of use, compatibility, trustworthy, interpersonal influence, external influence, self-efficacy and facilitating conditions. Therefore, it is hoped that this study will help academic and practical field to understand these phenomena as well as provided guidance for the policymakers to review e-Commerce ecosystem and mechanism to further expand the participation of SMEs in e-Commerce. [ABSTRACT FROM AUTHOR]

Lichen natural products are a tremendous source of new bioactive chemical entities for drug discovery. The ability to survive in harsh conditions can be directly correlated with the production of some unique lichen metabolites. Despite the potential applications, these unique metabolites have been underutilized by pharmaceutical and agrochemical industries due to their slow growth, low biomass availability, and technical challenges involved in their artificial cultivation. At the same time, DNA sequence data have revealed that the number of encoded biosynthetic gene clusters in a lichen is much higher than in natural products, and the majority of them are silent or poorly expressed. To meet these challenges, the one strain many compounds (OSMAC) strategy, as a comprehensive and powerful tool, has been developed to stimulate the activation of silent or cryptic biosynthetic gene clusters and exploit interesting lichen compounds for industrial applications. Furthermore, the development of molecular network techniques, modern bioinformatics, and genetic tools is opening up a new opportunity for the mining, modification, and production of lichen metabolites, rather than merely using traditional separation and purification techniques to obtain small amounts of chemical compounds. Heterologous expressed lichen-derived biosynthetic gene clusters in a cultivatable host offer a promising means for a sustainable supply of specialized metabolites. In this review, we summarized the known lichen bioactive metabolites and highlighted the application of OSMAC, molecular network, and genome mining-based strategies in lichen-forming fungi for the discovery of new cryptic lichen compounds. [ABSTRACT FROM AUTHOR]

The large oil palm plantation in Malaysia is located in Sabah which is around 700,000 acres of land that produces around 0.7 million tons of agricultural waste. The conversion of agriculture waste to activated carbon (AC) solves the disposal problem in the agricultural industry. The AC plays an important role as an electrode in supercapacitor due to its characteristics such as high porosity and good conductivity. The performance of supercapacitor electrodes was study by using different sizes of AC. The AC from oil palm kernel shell (PKS) was produced by using the low cost of production with a simple modification in a conventional method. The PKS carbonizes in a furnace at 390 oC for 1 hour. It soaks in KOH for chemical activation. The sample is rushed by using agate mortar to get two different sizes which is fine and coarse. The AC is then mixed for the preparation of the electrode labelled as (Sample 1, Sample 2 & Sample 3). Then, the electrode is assembled with filter paper as separator and 1.0 M KOH as electrolyte. The supercapacitor electrode is connected to the circuit to observe the potential of charge-discharge. The result of capacitance for Sample 1 is 26.3mF, specific capacitance 21.58mF/g and energy density 17.22Wh/kg while the Sample 2 of activated carbon is 2672.38mF, 1113.49 mF/g and energy density 52.384Wh/kg and Sample 3 is 2952.5mF, specific capacitance 1230.16mF/g and energy density 226.34Wh/kg. As conclusion, a high-performance capacitor is achieved by using a mixed size of PKS as active material in electrode. Therefore, PKS has large market potential due to the low-cost AC production but promises high performance in Supercapacitor Application.

Two Streptomyces strains, named N11-26 and DC10-5, were isolated from deep-sea and non-photosynthetic stony coral, respectively. Strain N11-26 produces lobophorin C and divergolides, which are antimicrobial substances. This study aimed to classify these strains and reveal their cryptic potential to synthesize other secondary metabolites, such as polyketides and nonribosomal peptides. Strains N11-26 and DC10-5 showed 16S rRNA gene sequence similarities of 100% and 99.9% to Streptomyces olivaceus NRRL B-3009T, respectively. By digital DNA–DNA hybridization using whole-genome sequences, these strains were classified as Streptomyces olivaceus. Strain N11-26 was closer to the type strain of S. olivaceus than strain DC10-5 and possessed 17 clusters of polyketide synthase (PKS) and/or nonribosomal peptide synthetases (NRPS) genes, whereas strain DC10-5 harbored 19 clusters. Putative products by these gene clusters were predicted by bioinformatic analyses. Although 15 clusters were conserved between the two strains, two and four clusters were specific in strains N11-26 and DC10-5, respectively. This represents a diversity of potential polyketide and nonribosomal peptide compounds between strains of S. olivaceus. To the best of our knowledge, this is the first report annotating all the PKS and NRPS gene clusters in S. olivaceus strains with their putative products to provide useful information for genome mining. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), encodes a family of membrane proteins belonging to Resistance-Nodulation-Cell Division (RND) permeases also called multidrug resistance pumps. Mycobacterial membrane protein Large (MmpL) transporters represent a subclass of RND transporters known to participate in exporting of lipid components across the cell envelope. These proteins perform an essential role in MTB survival; however, there are no data regarding mutations in MmpL, polyketide synthase (PKS) and acyl-CoA dehydrogenase FadE proteins from Khyber Pakhtunkhwa, Pakistan. This study aimed to screen mutations in transmembrane transporter proteins including MmpL, PKS and Fad through whole-genome sequencing (WGS) in local isolates of Khyber Pakhtunkhwa province, Pakistan. Fourteen samples were collected from TB patients and drug susceptibility testing was performed. However, only three samples were completely sequenced. Moreover, 209 whole-genome sequences of the same geography were also retrieved from NCBI GenBank to analyze the diversity of mutations in MmpL, PKS and Fad proteins. Among the 212 WGS (Accession ID: PRJNA629298 , PRJNA629388 , and ERR2510337-ERR2510345 , ERR2510546-ERR2510645), numerous mutations in Fad (n  = 756), PKS (n  = 479), and MmpL (n  = 306) have been detected. Some novel mutations were also detected in MmpL, PKS and acyl-CoA dehydrogenase Fad. Novel mutations including Asn576Ser in MmpL8, Val943Gly in MmpL9 and Asn145Asp have been detected in MmpL3. The presence of a large number of mutations in the MTB membrane may have functional consequences on proteins. However, further experimental studies are needed to elucidate the variants' effect on MmpL, PKS and FadE functions. [ABSTRACT FROM AUTHOR]

Malaysia’s palm oil industry generates a huge amount of palm kernel shell (PKS) waste. Utilising PKS as a sand replacement in brick production is one of the viable solutions to reduce biomass waste. The water absorption test revealed that the char-PKS absorbs significantly more water than the PKS-brick. The compression strength indicated that PKS masonry bricks meet Malaysian standards and American Society for Testing and Materials. According to the density test, the bricks with the maximum sand replacement fall into the lightweight range. This research has sparked hope of reducing PKS waste by using it as a partial replacement for sand in brick production.

The growing global threat of antimicrobial resistance is reaching a crisis point as common bacterial infections, including those caused by pathogenic Neisseria species, are becoming increasingly untreatable. This is compelling the scientific community to search for new antimicrobial agents, taking advantage of computational mining and using whole genome sequences to discover natural products from the human microbiome with antibiotic effects. In this study, we investigated the crude extract from a Rothia dentocariosa strain with demonstrated antimicrobial activity against pathogenic Neisseria spp. by spot-on-lawn assay. The genomic DNA of the R. dentocariosa strain was sequenced, and bioinformatic evaluation was performed using antiSMASH and PRISM to search for biosynthetic gene clusters (BGCs). The crude extract with potential antimicrobial activity was run on Tricine-SDS-PAGE, and the putative peptides were characterised using liquid chromatography–tandem mass spectrometry (LC-MS). The crude extract inhibited the growth of the pathogenic Neisseria spp. Six BGCs were identified corresponding to non-ribosomal peptide synthases (NRPSs), polyketide synthases (PKSs), and ribosomally synthesised and post-translationally modified peptides. Three peptides were also identified corresponding to Actinorhodin polyketide putative beta-ketoacyl synthase 1. These findings serve as a useful reference to facilitate the research and development of NRPS and PKS as antimicrobial products against multidrug-resistant N. gonorrhoeae.

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Sponge-derived bacteria are considered to be a promising source of novel drugs, owing to their abundant secondary metabolites that have diverse biological activities. In this study, we explored the antimicrobial biosynthetic potential and phylogenetics of culturable bacteria associated with the sponge Ophlitaspongia sp. from the Yellow Sea, China. Using culture-dependent methods, we obtained 151 bacterial strains, which were then analysed for their antimicrobial activities against seven indicator strains. The results indicate that 94 (62.3%) of the 151 isolated strains exhibited antimicrobial activities and inhibited at least one of the indicator strains. Fifty-two strains were selected for further phylogenetic analysis using 16S rRNA gene sequencing, as well as for the presence of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes. These 52 strains belonged to 20 genera from 18 families in 4 phyla, including Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Five strains with PKS genes and ten strains with NRPS genes were detected. Among them, two strains contained both PKS and NRPS genes. Notoacmeibacter sp. strain HMA008 (class Alphaproteobacteria) exhibited potent antimicrobial activity; thus, whole genome sequencing methods were used to analyse its secondary metabolite biosynthetic gene clusters. The genome of HMA008 contained 12 biosynthetic gene clusters that potentially encode secondary metabolites belonging to compound classes such as non-ribosomal peptides, prodigiosin, terpene, β-lactones, and siderophore, among others. This study indicates that the sponge Ophlitaspongia sp. harbours diverse bacterial strains with antimicrobial properties and may serve as a potential source of bioactive compounds. [ABSTRACT FROM AUTHOR]

Fungal secondary metabolites (SMs) comprise a vast collection of compounds expendable for these organisms under laboratory conditions. They exhibit enormous chemical diversity, and usually belong to four major families: terpenoids, polyketides, non-ribosomal peptides, or a combination of the last two. Their functions are very diverse and are normally associated with a greater fitness of the producing fungi in their environment, which often compete with other microorganisms or interact with host plants. Many SMs have beneficial applications, e.g., as antibiotics or medical drugs, but others, known as mycotoxins, are harmful to health.

Background and Aim: Actinomycetes are a group of Gram-positive bacteria with a fungus-like morphology. Their natural habitat encompasses terrestrial and water areas, including mangrove ecosystems. This study aimed to assess the PKS and NRPS genes as the producers of secondary metabolites and to determine the target bacterial species using molecular DNA tests. Materials and Methods: In this study, we isolated bacteria from sediment samples from mangrove forests located on Karimunjawa Islands and in Semarang city, purified bacteria, screened for antibacterial activity, extracted bacterial DNA, amplified the NRPS gene, detected and amplified the PKS-I and PKS-II genes, amplified and sequenced the 16S rRNA, processed molecular data, and simulated a map of secondary metabolite producing genes. Results: Samples from the Karimunjawa Islands yielded 19 bacterial isolates, whereas samples from Semarang yielded 11 bacterial isolates after culture in different media. Further experiments identified three active isolates, which were termed PN.SB.6.2, S.SK.6.3, and S.SK.7.1, against pathogenic species of Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. Isolate PN.SB.6.2 was determined to possess three biosynthetic gene clusters (BGCs), whereas the remaining two isolates, S.SK.6.3 and S.SK.7.1, only possessed two BGCs, namely, NRPS and PKS II. Conclusion: Products were estimated to be in the NRPS, thiopeptide, RiPP-like, siderophore, betalactone, terpene, Type III PKS, CDPS, and lassopeptide groups. DNA identification of the isolates found three species of actinomycetes with antibacterial potential, namely, Virgibacillus salaries, Bacillus licheniformis, and Priestia flexa.

This research aims to understand the shifting of political education at Partai Keadilan Sejahtera (Prosperity and Justice Party (PKS). I employ theory of social contract to analyze phenomena involving the elites and the rest of the Muslims. This research is a study of the literature complemented with an in-depth interview with those who involve in the political education either as the subjects or objects of it. The data, then, were analyzed by means of a method of critical discourse. The political education shifting, partly, is related to the shifting of conception on the relationship between Islam, as normative values, and Indonesia, as the context for its implementation. At first, PKS tends to produce a cadre who has strong characters such as a pious cadre and loyal to the party. Majority of the elite party failed to represent themselves at the Parliament. Then, they develop political education which produces activists who are capable of accommodating Islamic values to the political calculation. At last, PKS follows the market demand of middle class Muslims who aspire to produce the religious and modern young Muslim generation. By so doing, PKS is able to expand its political influence amongst the people, especially the Muslim.

Dinoflagellates are unicellular organisms that are implicated in harmful algal blooms (HABs) caused by potent toxins that are produced through polyketide synthase (PKS) pathways. However, the exact mechanisms of toxin synthesis are unknown due to a lack of genomic segregation of fat, toxins, and other PKS-based pathways. To better understand the underlying mechanisms, the actions and expression of the PKS proteins were investigated using the toxic dinoflagellate Amphidinium carterae as a model. Cerulenin, a known ketosynthase inhibitor, was shown to reduce acetate incorporation into all fat classes with the toxins amphidinol and sulpho-amphidinol. The mass spectrometry analysis of cerulenin-reacted synthetic peptides derived from ketosynthase domains of A. carterae multimodular PKS transcripts demonstrated a strong covalent bond that could be localized using collision-induced dissociation. One multi-modular PKS sequence present in all dinoflagellates surveyed to date was found to lack an AT domain in toxin-producing species, indicating trans-acting domains, and was shown by Western blotting to be post-transcriptionally processed. These results demonstrate how toxin synthesis in dinoflagellates can be differentiated from fat synthesis despite common underlying pathway.

Simple Summary: Fungi can produce many types of secondary metabolites, including mycotoxins. Poisonous mushrooms and mycotoxins that cause food spoilage have been known for a very long time. For example, Aspergillus flavus, which can grow on grains and nuts, produces highly toxic substances called Aflatoxins. Despite their menace to other living organisms, mycotoxins can be used for medicinal purposes, i.e., as antibiotics, growth-promoting compounds, and other kinds of drugs. These and other secondary metabolites produced by plant-pathogenic fungi may cause host plants to display disease symptoms and may play a substantial role in disease progression. Therefore, the identification and characterization of the genes involved in their biosynthesis are essential for understanding the molecular mechanism involved in their biosynthetic pathways and further promoting sustainable knowledge-based crop production. Polyketides are structurally diverse and physiologically active secondary metabolites produced by many organisms, including fungi. The biosynthesis of polyketides from acyl-CoA thioesters is catalyzed by polyketide synthases, PKSs. Polyketides play roles including in cell protection against oxidative stress, non-constitutive (toxic) roles in cell membranes, and promoting the survival of the host organisms. The genus Verticillium comprises many species that affect a wide range of organisms including plants, insects, and other fungi. Many are known as causal agents of Verticillium wilt diseases in plants. In this study, a comparative genomics approach involving several Verticillium species led us to evaluate the potential of Verticillium species for producing polyketides and to identify putative polyketide biosynthesis gene clusters. The next step was to characterize them and predict the types of polyketide compounds they might produce. We used publicly available sequences from ten species of Verticillium including V. dahliae, V. longisporum, V. nonalfalfae, V. alfalfae, V. nubilum, V. zaregamsianum, V. klebahnii, V. tricorpus, V. isaacii, and V. albo-atrum to identify and characterize PKS gene clusters by utilizing a range of bioinformatic and phylogenetic approaches. We found 32 putative PKS genes and possible clusters in the genomes of Verticillium species. All the clusters appear to be complete and functional. In addition, at least five clusters including putative DHN-melanin-, cytochalasin-, fusarielien-, fujikurin-, and lijiquinone-like compounds may belong to the active PKS repertoire of Verticillium. These results will pave the way for further functional studies to understand the role of these clusters. [ABSTRACT FROM AUTHOR]

Dinoflagellates play important roles in ecosystems as primary producers and consumers making natural products that can benefit or harm environmental and human health but are also potential therapeutics with unique chemistries. Annotations of dinoflagellate genes have been hampered by large genomes with many gene copies that reduce the reliability of transcriptomics, quantitative PCR, and targeted knockouts. This study aimed to functionally characterize dinoflagellate proteins by testing their interactions through in vitro assays. Specifically, nine Amphidinium carterae thiolation domains that scaffold natural product synthesis were substituted into an indigoidine synthesizing gene from the bacterium Streptomyces lavendulae and exposed to three A. carterae phosphopantetheinyl transferases that activate synthesis. Unsurprisingly, several of the dinoflagellate versions inhibited the ability to synthesize indigoidine despite being successfully phosphopantetheinated. However, all the transferases were able to phosphopantetheinate all the thiolation domains nearly equally, defying the canon that transferases participate in segregated processes via binding specificity. Moreover, two of the transferases were expressed during growth in alternating patterns while the final transferase was only observed as a breakdown product common to all three. The broad substrate recognition and compensatory expression shown here help explain why phosphopantetheinyl transferases are lost throughout dinoflagellate evolution without a loss in a biochemical process. [ABSTRACT FROM AUTHOR]

Metabolic engineering efforts toward rewiring metabolism of cells to produce new compounds often require the utilization of non-native enzymatic machinery that is capable of producing a broad range of chemical functionalities. Polyketides encompass one of the largest classes of chemically diverse natural products. With thousands of known polyketides, modular polyketide synthases (PKSs) share a particularly attractive biosynthetic logic for generating chemical diversity. The engineering of modular PKSs could open access to the deliberate production of both existing and novel compounds. In this review, we discuss PKS engineering efforts applied at both the protein and cellular level for the generation of a diverse range of chemical structures, and we examine future applications of PKSs in the production of medicines, fuels and other industrially relevant chemicals.

The health problems associated with the use of asbestos based brake linings have motivated research on the use of ecofriendly-agro based biomaterials as reinforcing agents in composite materials used for brake pad lining production. This research work studies the possibilities of using palm kernel shell (PKS), coconut shell (CNS), and canarium sweinfurthii shell (CSS) powder for asbestos-free brake lining materials production. The powders alongside the relevant fillers were used in the production of the brake lining. Compositions of the reinforcing powders were varied from 25% to 40% thatof resin binder was varied from 58% to 43%, while those of filler metal and curing agents were kept constant. These materials were weighed, formulated, mixed, cured, and moulded. The developed composite materials were characterized and subjected to water and oil absorption, compressive strength, hardness, and wear tests. Results of the analysis revealed that increase in reinforcing materials results in an increase in the water and oil absorption of the samples. The composite’s compressive strength equally increased with the introduction of up to 35% composition. The measured value of coefficient of friction was found to be within an acceptable range. Also, when mixed with other fillers and bounded, CSS powder proved to be a very promising material for brake lining production.

Fungi are important sources for the discovery of natural products. During the last decades, technological progress and the increasing number of sequenced genomes facilitated the exploration of new secondary metabolites. Among those, polyketides represent a structurally diverse group with manifold biological activities. In this study, we successfully used genome mining and genetic manipulation for functional proof of a polyketide biosynthetic gene cluster from the filamentous fungus Penicillium crustosum. Gene activation in the native host and heterologous expression in Aspergillus nidulans led to the identification of the xil cluster, being responsible for the formation of the 6-methyl-2-pyrone derivative xylariolide D. Feeding with 13C-labeled precursors supported the hypothesis of chain branching during the backbone formation catalyzed by a highly reducing fungal polyketide synthase. A cytochrome P450-catalyzed hydroxylation converts the PKS product to the final metabolite. This proved that just two enzymes are required for the biosynthesis of xylariolide D. [ABSTRACT FROM AUTHOR]

The greatest challenge associated with topical drug delivery for the treatment of diseases affecting the posterior segment of the eye is to overcome the poor bioavailability of the carried molecules. Nanomedicine offers the possibility to overcome obstacles related to physiological mechanisms and ocular barriers by exploiting different ocular routes. Functionalization of nanosystems by fluorescent probes could be a useful strategy to understand the pathway taken by nanocarriers into the ocular globe and to improve the desired targeting accuracy. The application of fluorescence to decorate nanocarrier surfaces or the encapsulation of fluorophore molecules makes the nanosystems a light probe useful in the landscape of diagnostics and theranostics. In this review, a state of the art on ocular routes of administration is reported, with a focus on pathways undertaken after topical application. Numerous studies are reported in the first section, confirming that the use of fluorescent within nanoparticles is already spread for tracking and biodistribution studies. The first section presents fluorescent molecules used for tracking nanosystems' cellular internalization and permeation of ocular tissues; discussions on the classification of nanosystems according to their nature (lipid-based, polymer-based, metallic-based and protein-based) follows. The following sections are dedicated to diagnostic and theranostic uses, respectively, which represent an innovation in the ocular field obtained by combining dual goals in a single administration system. For its great potential, this application of fluorescent nanoparticles would experience a great development in the near future. Finally, a brief overview is dedicated to the use of fluorescent markers in clinical trials and the market in the ocular field. [ABSTRACT FROM AUTHOR]

Malaysia’s palm oil industry generates a huge amount of palm kernel shell (PKS) waste. Utilising PKS as a sand replacement in brick production is one of the viable solutions to reduce biomass waste. The water absorption test revealed that the char-PKS absorbs significantly more water than the PKS-brick. The compression strength indicated that PKS masonry bricks meet Malaysian standards and American Society for Testing and Materials. According to the density test, the bricks with the maximum sand replacement fall into the lightweight range. This research has sparked hope of reducing PKS waste by using it as a partial replacement for sand in brick production. [ABSTRACT FROM AUTHOR]

Trichoderma reesei (Hypocrea jecorina) was developed as a microbial cell factory for the heterologous expression of fungal secondary metabolites. This was achieved by inactivation of sorbicillinoid biosynthesis and construction of vectors for the rapid cloning and expression of heterologous fungal biosynthetic genes. Two types of megasynth(et)ases were used to test the strain and vectors, namely a non-reducing polyketide synthase (nr-PKS, aspks1) from Acremonium strictum and a hybrid highly-reducing PKS non-ribosomal peptide synthetase (hr-PKS-NRPS, tenS + tenC) from Beauveria bassiana. The resulting engineered T. reesei strains were able to produce the expected natural products 3-methylorcinaldehyde and pretenellin A on waste materials including potato, orange, banana and kiwi peels and barley straw. Developing T. reesei as a heterologous host for secondary metabolite production represents a new method for waste valorization by the direct conversion of waste biomass into secondary metabolites. [ABSTRACT FROM AUTHOR]

Photosynthetic dinoflagellates synthesize many toxic but also potential therapeutic compounds therapeutics via polyketide/non-ribosomal peptide synthesis, a common means of producing natural products in bacteria and fungi. Although canonical genes are identifiable in dinoflagellate transcriptomes, the biosynthetic pathways are obfuscated by high copy numbers and fractured synteny. This study focuses on the carrier domains that scaffold natural product synthesis (thiolation domains) and the phosphopantetheinyl transferases (PPTases) that thiolate these carriers. We replaced the thiolation domain of the indigoidine producing BpsA gene from Streptomyces lavendulae with those of three multidomain dinoflagellate transcripts and coexpressed these constructs with each of three dinoflagellate PPTases looking for specific pairings that would identify distinct pathways. Surprisingly, all three PPTases were able to activate all the thiolation domains from one transcript, although with differing levels of indigoidine produced, demonstrating an unusual lack of specificity. Unfortunately, constructs with the remaining thiolation domains produced almost no indigoidine and the thiolation domain for lipid synthesis could not be expressed in E. coli. These results combined with inconsistent protein expression for different PPTase/thiolation domain pairings present technical hurdles for future work. Despite these challenges, expression of catalytically active dinoflagellate proteins in E. coli is a novel and useful tool going forward. [ABSTRACT FROM AUTHOR]

The novel biologically active molecules could play a significant role in the treatment of human diseases. Natural products have been and continue to be a major source of pharmaceuticals, and lichen secondary metabolites emerge as never-ending potential for bioactive molecules with a variety of pharmacological activities. Polyketides, which are synthesized by enzymes encoded by PKS genes, constitute the major group of these secondary metabolites. To date, there is a lack of information about identification of PKS gene modules. Functional validation studies in lichens are difficult because of the slow growth rates of lichens, the symbiotic partners of lichens cannot be cultured in the laboratory or the fact that most of them cannot be grown in culture. Consequently, the importance of genomic mining approach is increasing as a unique tool for natural product discovery studies. Here, we bioinformatically investigated the type I PKS module candidates in nine publicly available lichen-forming fungi genomes through the use of the in silico screening tools. We also predicted putative secondary metabolites produced in these lichens which indicated the pharmaceutical potential of these nine lichen-forming fungi by bioinformatics tools.

Definition: Fungal secondary metabolites (SMs) comprise a vast collection of compounds expendable for these organisms under laboratory conditions. They exhibit enormous chemical diversity, and usually belong to four major families: terpenoids, polyketides, non-ribosomal peptides, or a combination of the last two. Their functions are very diverse and are normally associated with a greater fitness of the producing fungi in their environment, which often compete with other microorganisms or interact with host plants. Many SMs have beneficial applications, e.g., as antibiotics or medical drugs, but others, known as mycotoxins, are harmful to health. [ABSTRACT FROM AUTHOR]

The development of Islam in the political arena in Indonesia is interesting to be analyzed comprehensively. The purpose of this paper is to analyze the existence of Islamic political parties after the 2019 simultaneous general elections. The main problem in political life in Indonesia is the decline of public trust in political parties. One of the main reasons is the corruption case that ensnared politicians. The presence of Islamic political parties is hopefully able to bring a change and alter the ugly stigma from the society towards the political parties. This study is qualitative in nature with a case study of PKS as a participant in the 2019 simultaneous general election, using an institutional assessment of the existence of political parties. The dynamics and existence of PKS before the 2019 general election were categorically high. It means that the PKS movement was active in society by offering strategic programs and policies for voters. PKS has a structured party system starting from the regeneration system to constituent treatment that can increase the number of voters in the 2019 elections. This research shows that regeneration carried out through tarbiyah can instill party ideology in cadres, but fails to raise the party in a fast time. Based on the political dynamics of PKS during the Jokowi-JK administration period 2014-2019, identity politics was able to increase voter participation and increase PKS votes in the 2019 elections.

Abstract Background Colon cancer is one of the most common malignancies and the fourth leading cause of cancer-related mortality in the world. Colibactin, which is synthesized by the pks genomic island of E. coli interfere with the eukaryotic cell cycle. Cinnamon has an antimicrobial effect and considered as a colon cancer-preventing agent. The aim of the study was to evaluate the effects of cinnamon extract and cinnamaldehyde on clbB gene expression and biofilm formation in clinical isolates of E. coli. Methods Thirty E. coli carrying pks gene were isolated from the colon cancer patients, inflammatory bowel disease and healthy subjects. Antibiotic susceptibility was evaluated by disk diffusion method and the minimum inhibitory concentration of cinnamon essential oil and cinnamaldehyde by microdilution broth method. In vitro biofilm formation of E.coli isolates was monitored using a microtiter plate method. The presence of clbB, clbA and clbQ genes in E.coli isolates were evaluated by PCR. The effect of cinnamaldehyde and cinnamon essential oil on clbB gene expression was evaluated by Real-Time PCR. Results The highest antibiotic resistance was obtained with 94.4% for ticarcillin-clavulanic acid, azithromycin, amoxicillin, and amikacin. The MIC for all clinical isolates was 32 μl/ml of cinnamon essential oil and the MIC of cinnamaldehyde was between 0.00002 to 0.03 μl/ml. After exposure of isolates to cinnamon extract and cinnamaldehyde, 40 and 13.3% were weakly biofilm producers, respectively. The frequencies of clbB, clbA, and clbQ genes were 23.3, 23.3, and 26.7%, respectively. The expression of clbB gene in the presence of the Sub-MIC concentration of cinnamon essential oil and cinnamaldehyde was decreased in 8 isolates compared to untreated isolates (p-value

Objectives: Pallister-Killian syndrome (PKS) is a rare genetic disorder with multi-organ involvement caused by mosaic tetrasomy of chromosome 12p. Although many caregivers report the presence of impaired sleep in their children, there are no clear data in the literature on this issue and no systematic study has ever been performed. With this study, we aimed to characterize the features of sleep in Pallister-Killian syndrome and identify the possible influence of clinical and demographic features. Moreover, our aim was to verify the effectiveness of conventional screening questionnaires in this particular group of patients. Methods: We prospectively enrolled 14 patients aged 1–17 years in collaboration with PKS Kids Italia ONLUS. The Sleep Disturbance Scale for Children (SDSC) questionnaire was administered to caregivers. Then, video polysomnography (VPSG) of at least 24 h was performed and results were compared with a same-aged control group. Results: A total of 92% of patients had abnormal SDSC scores, extremely high in the "disorder of initiating and maintaining sleep" (DIMS) and "sleep breathing disorders" (SBD) subscales. VPSG showed a significantly impaired macrostructure in PKS patients, with a higher Arousal Index (p < 0.00001) and percentage of time spent in N3 (p < 0.00001), and reduced Sleep Efficiency (p = 0.0006). After dividing both PKS and controls into two groups based on median age, some peculiarities emerged: the younger group had higher Awakenings Index (p = 0.0207) and percentage of time spent in N1 (p = 0.015) while the older group showed higher time in bed (TIB) (p = 0.0485), compared with controls. Due to poor compliance, the Apnea-Hypopnea Index (AHI) was evaluated only for 10 PKS children, being significantly increased (p = 0.0427) compared with controls. SBD subscale scores in SDSC were significantly related to AHI values in VPSG (p = 0.0099). Conclusions: This study constitutes the first attempt to describe the sleep pattern in PKS. Despite small numbers due to the rarity of the syndrome, our VPSG results confirm the high prevalence of sleep disorders (SDs) in these patients. It is therefore essential to investigate and treat them. The SDSC scale is a good screening tool for early detection also in these patients, with particular sensitivity in detecting breathing disorders. [ABSTRACT FROM AUTHOR]

Actinobacteria isolated from marine sources are a potential source of novel natural products. In this study, we report isolation, biological activity and characterization of secondary metabolites from strain Nocardiopsis sp. SCA30, isolated from marine sediments of Havelock Islands, Andaman and Nicobar, India. The ethyl acetate extracts of the isolate on screening for biological activity demonstrated antibacterial potency and antiproliferative activity. The extracts showed anticancer activity in a panel of cell lines, including HCT 15, HT 29, MCF 7 and MDA-MB 468, at concentrations ranging from 62.5 to 1000 µg/ml. A dose-dependent reduction in cell viability was observed in all the tested cell lines. The extract at 15 µg/ml and 30 µg/ml inhibited growth of methicillin-resistant Staphylococcus aureus ATCC NR-46071 and NR-46171 with MIC's of 15.62 and 7.81 µg/ml, respectively. LC–MS and NMR studies revealed that the antibacterial and anticancer compound isolated from Nocardiopsis sp. SCA30 is 1-acetyl-4-4(hydroxyphenyl)piperazine. [ABSTRACT FROM AUTHOR]

Aims: Microbial endophytes produce specialized metabolites, including antibiotics and other compounds of pharmaceutical and agricultural value. This study aimed to investigate the diversity and bioactivity of endophytes from medicinal plants used by the Dharawal People of Gamay (Botany Bay), Australia. Methods and Results: Of the 48 endophytes isolated, 19 tested positive for polyketide synthase or non‐ribosomal peptide synthetase genes via a PCR incorporating degenerate primers. The biosynthetically talented endophytes were identified by 16S rRNA gene sequencing and included 4 bacteria species belonging to the orders Bacillales, Rhizobiales and Burkholderiales and 15 Ascomycota fungi species belonging to the orders Botryosphaeriales, Cladosporiales, Glomerellales, Microascales and Eurotiales. Antimicrobial testing using the disc diffusion assay demonstrated that 15 of the 19 isolates had broad‐spectrum activity against a range of Gram‐positive and Gram‐negative bacteria. Conclusions: Taken together, these results suggest that Australian bush medicines harbour diverse biosynthetically talented microbial endophytes capable of producing broad‐spectrum antibacterial compounds. Significance and Impact of the Study: This study suggests that compounds produced by microbial endophytes likely contribute to the collective medicinal properties of Australian bush medicines. Significantly, it highlights that Indigenous botanical knowledge and modern molecular approaches can be used in tandem to prioritize microorganisms that produce pharmaceutically relevant compounds. [ABSTRACT FROM AUTHOR]

Background and Aim: Actinomycetes are a group of Gram-positive bacteria with a fungus-like morphology. Their natural habitat encompasses terrestrial and water areas, including mangrove ecosystems. This study aimed to assess the PKS and NRPS genes as the producers of secondary metabolites and to determine the target bacterial species using molecular DNA tests. Materials and Methods: In this study, we isolated bacteria from sediment samples from mangrove forests located on Karimunjawa Islands and in Semarang city, purified bacteria, screened for antibacterial activity, extracted bacterial DNA, amplified the NRPS gene, detected and amplified the PKS-I and PKS-II genes, amplified and sequenced the 16S rRNA, processed molecular data, and simulated a map of secondary metabolite producing genes. Results: Samples from the Karimunjawa Islands yielded 19 bacterial isolates, whereas samples from Semarang yielded 11 bacterial isolates after culture in different media. Further experiments identified three active isolates, which were termed PN.SB.6.2, S.SK.6.3, and S.SK.7.1, against pathogenic species of Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. Isolate PN.SB.6.2 was determined to possess three biosynthetic gene clusters (BGCs), whereas the remaining two isolates, S.SK.6.3 and S.SK.7.1, only possessed two BGCs, namely, NRPS and PKS II. Conclusion: Products were estimated to be in the NRPS, thiopeptide, RiPP-like, siderophore, betalactone, terpene, Type III PKS, CDPS, and lassopeptide groups. DNA identification of the isolates found three species of actinomycetes with antibacterial potential, namely, Virgibacillus salaries, Bacillus licheniformis, and Priestia flexa. [ABSTRACT FROM AUTHOR]