Bright Structural-Phase-Pure CsPbI3 Core-PbSO4 Shell Nanoplatelets With Ultra-Narrow Emission Bandwidth of 77 meV at 630 nm.

Achieving a narrow emission bandwidth is long pursued for display applications. Among all primary colors, obtaining pure red emission with high visual perception is the most challenging. In this work, CsPbI3 halide perovskite nanoplatelets (NPLs) with rigorously controlled 2D  [PbI6]4- octahedron layer number (n) are demonstrated. A perovskite core-PbSO4 shell structure is designed to prevent aggregation and fusion between NPLs, enabling consistent thickness and quantum confinement strength for each NPL. Consequently, exact n = 4 CsPbI3 NPLs are demonstrated, exhibiting emission peaks around 630 nm, with very narrow spectral bandwidths of <24 nm and high absolute photoluminescence quantum yields up to 85%. The emission of n = 4 NPLs falls exactly within the pure-red region, closely aligning with the International Telecommunication Union Recommendation BT.2020  standard. Measurements suggest predominant stability and color homogeneity compared to traditional red-emitting CsPbIxBr3- x nanocrystals. Finally, proof-of-concept pure-red emissive light-emitting diodes (LEDs) are demonstrated by integrating n = 4 CsPbI3 NPLs films with a blue LED chip, showing an excellent external quantum efficiency of 18.3% and high brightness exceeding 3 × 106 nits. Stringent requirements for future display technologies, are satisfied based on the high color purity, stability, and brightness of CsPbI3 NPLs.

[Current Situation and Influencing Factors of Kindergarten Teachers' Participation in Training for Preschool Sex Education].

Objective To understand the current situation and influencing factors of kindergarten teachers' participation in training for preschool sex education in Luzhou city,and provide a basis for improving the sex education literacy of kindergarten teachers in the future. Methods A multi-stage stratified cluster sampling method was adopted,and a questionnaire survey was conducted from December 2021 to January 2022 on the knowledge,attitude,and practice of preschool sex education among all the teachers in 24 kindergartens in Luzhou city. Results Among the 461 teachers,43.0% had participated in lectures/courses/training activities related to preschool sex education;99.1% hoped to participate in lectures/courses/training activities related to preschool sex education;82.6% learned about child sexual knowledge through school education;75.5% expressed the hope to learn about child sexual knowledge through expert training.The results of multivariate Logistic regression showed that except private kindergartens as an inhibiting factor (OR=0.57,95%CI=0.37-0.87,P=0.008),high monthly income (OR=3.52,95%CI=1.13-9.30,P=0.011),more ways to know about sex education knowledge (OR=2.87,95%CI=1.76-4.70,P<0.001),and social support (OR=1.58,95%CI=1.04-2.38, P=0.030) were promoting factors for teachers to participate in the training for preschool sex education. Conclusion The kindergarten teachers presented a participation rate but a high demand for the training for preschool sex education.They mainly obtain the sex education knowledge from school education.The nature of kindergarten,monthly income of teachers,social support situation,and ways of understanding sex education knowledge are the key factors influencing the teachers' participation in the training for preschool sex education.

Diterpenoids of Caryopteris trichosphaera W. W. Sm. inhibiting MRSA and VRE in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Caryopteris trichosphaera W. W. Sm., a traditional ethnic medicine, was recorded in the Compendium of Materia Medica for treating wound infection by pathogenic infection. However, its antibacterial potential and bioactive compositions against drug-resistant bacteria need to be validated. AIM OF THE STUDY: To investigate the chemical constituents of C. trichosphaera and explore its anti-MRSA component in vitro and in vivo, together with the antibacterial mechanism. MATERIALS AND METHODS: Bioactive constituents investigation was carried out by phytochemical method and antibacterial screening. The antibacterial mechanism was predicted by network pharmacology, which was further validated by time-kill analysis, membrane function tests, multigenerational resistance induction assay and biofilm test, and metabolomics analysis in vitro. In addition, MRSA-induced epidermal infection in mice was selected to evaluate its pharmacological effect in vivo. RESULTS: Six antibacterial diterpenoids against MRSA and VRE with MIC values 4-32 µg/mL from C. trichosphaera were reported for the first time, in which the major compound cativic acid (1) disrupted MRSA cell membranes by modulating permeability, depolarization, and fluidity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It also displayed remarkable anti-biofilm activity without inducing bacterial resistance or cytotoxicity. Moreover, cativic acid affected MRSA biosynthesis of cofactors, amino acid biosynthesis, nucleotide metabolism by metabolomics analysis. Furthermore, cativic acid accelerated wound healing in MRSA-infected mouse skin wounds, even better than vancomycin. CONCLUSIONS: The results supported the traditional use of C. trichosphaera, and presented unreported anti-MRSA agent, cativic acid, as a plant-derived bactericide in vitro and in vivo for the first time.

Cystoderma yongpingense sp. nov. (Squamanitaceae, Agaricales) a new species from southwestern China.

The present study introduces a novel fungus, Cystoderma yongpingense, which was identified in the southwestern region of China. The new species is characterized by a pileus that ranges in color from light orange-red to orange-red; the pileus has a wrinkled surface and is accompanied by a persistent annulus that is membranous and floccose-scaly. Above the annulus, the color transitions from white to yellowish brown. This proposal is substantiated through analyses encompassing both morphological characteristics and phylogenetic relationships. The phylogenetic position of the newly discovered species has been further corroborated through comprehensive maximum likelihood and Bayesian sequence analyses of the ITS + nrLSU DNA regions. Additionally, the technical description of C. yongpingense is enhanced by detailed illustrations and comparative studies with species that are closely related.

Natural and revolutionary tumor-specific T-cell therapy.

Recently the FDA conducted a risk investigation and labeled the Boxed Warning for all BCMA- and CD19-directed CAR-T cell therapy, so does it mean that the public must take risk of secondary cancer to receive cell therapy? Here, without lentivirus and professional antigen presenting cell application, a novel tumor-specific T-cell therapy was successfully developed only by co-culturing MHC+ cancer cells and Naïve-T cells under the CD28 co-stimulatory signals. These tumor-specific T-cells could be separated through cell size and abundantly produced from peripheral blood, and would spontaneously attack target cells that carrying the same tumor antigen while avoiding others in vitro test. Moreover, it markedly decreased 90% tumor nodules companying with greatly improving overall survival (76 days vs 30 days) after twice infusion back to mice. This work maximally avoided the risks of secondary cancer and non-specific killing, and might open a revolutionary beginning of natural tumor-specific T-cell therapy.

Exploring naphthoquinone and anthraquinone derivatives as antibiotic adjuvants against Staphylococcus aureus biofilms: Synergistic effects of menadione.

Given the ability of Staphylococcus aureus to form biofilms and produce persister cells, making infections difficult to treat with antibiotics alone, there is a pressing need for an effective antibiotic adjuvant to address this public health threat. In this study, a series of quinone derivatives were evaluated for their antimicrobial and antibiofilm activities against methicillin-susceptible and methicillin-resistant S. aureus reference strains. Following analyses using broth microdilution, growth curve analysis, checkerboard assay, time-kill experiments, and confocal laser scanning microscopy, menadione was identified as a hit compound. Menadione exhibited a notable antibacterial profile (minimum inhibitory concentration, MIC = 4-16 µg/ml; minimum bactericidal concentration, MBC = 256 µg/ml) against planktonic S. aureus and its biofilms (minimum biofilm inhibitory concentration, MBIC50 = 0.0625-0.25 µg/ml). When combined with oxacillin, erythromycin, and vancomycin, menadione exhibited a synergistic or additive effect against planktonic cells and biofilms of two S. aureus reference strains and six clinical isolates, highlighting its potential as a suitable adjuvant for further development against S. aureus biofilm-associated infections.

6-Methoxyldihydrochelerythrine Chloride Inhibiting Intra and Extracellular Drug-Resistant Bacteria.

Vancomycin-resistant enterococcus (VRE) is a major nosocomial pathogen that exhibits enhanced infectivity due to its robust virulence and biofilm-forming capabilities. In this study, 6-methoxyldihydrochelerythrine chloride (6-MDC) inhibited the growth of exponential-phase VRE and restored VRE's sensitivity to vancomycin. 6-MDC predominantly suppressed the de novo biosynthetic pathway of pyrimidine and purine in VRE by the RNA-Seq analysis, resulting in obstructed DNA synthesis, which subsequently weakened bacterial virulence and impeded intracellular survival. Furthermore, 6-MDC inhibited biofilm formation, eradicated established biofilms, reduced virulence, and enhanced the host immune response to prevent intracellular survival and replication of VRE. Finally, 6-MDC reduced the VRE load in peritoneal fluid and cells significantly in a murine peritoneal infection model. This paper provides insight into the potential antimicrobial target of benzophenanthridine alkaloids for the first time.

New resorcylic acid derivatives of Lysimachia tengyuehensis against MRSA and VRE by interfering with bacterial metabolic imbalance.

The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1-4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4-8 µg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time.

Structural basis of tethered agonism and G protein coupling of protease-activated receptors.

Protease-activated receptors (PARs) are a unique group within the G protein-coupled receptor superfamily, orchestrating cellular responses to extracellular proteases via enzymatic cleavage, which triggers intracellular signaling pathways. Protease-activated receptor 1 (PAR1) is a key member of this family and is recognized as a critical pharmacological target for managing thrombotic disorders. In this study, we present cryo-electron microscopy structures of PAR1 in its activated state, induced by its natural tethered agonist (TA), in complex with two distinct downstream proteins, the Gq and Gi heterotrimers, respectively. The TA peptide is positioned within a surface pocket, prompting PAR1 activation through notable conformational shifts. Contrary to the typical receptor activation that involves the outward movement of transmembrane helix 6 (TM6), PAR1 activation is characterized by the simultaneous downward shift of TM6 and TM7, coupled with the rotation of a group of aromatic residues. This results in the displacement of an intracellular anion, creating space for downstream G protein binding. Our findings delineate the TA recognition pattern and highlight a distinct role of the second extracellular loop in forming ß-sheets with TA within the PAR family, a feature not observed in other TA-activated receptors. Moreover, the nuanced differences in the interactions between intracellular loops 2/3 and the Gα subunit of different G proteins are crucial for determining the specificity of G protein coupling. These insights contribute to our understanding of the ligand binding and activation mechanisms of PARs, illuminating the basis for PAR1's versatility in G protein coupling.

Liver injury protection of Artemisia stechmanniana besser through PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia stechmanniana Besser, one of the most prevalent botanical medicines in Chinese, has been traditionally used for hepatitis treatment. However, the bioactive components and pharmacological mechanism on alcohol-induced liver injury remains unclear. AIM OF THE STUDY: To investigate the effect of A. stechmanniana on alcohol-induced liver damage, and further explore its mechanism. MATERIALS AND METHODS: Phytochemical isolation and structural identification were used to determine the chemical constituents of A. stechmanniana. Then, the alcohol-induced liver damage animal and cell model were established to evaluate its hepato-protective potential. Network pharmacology, molecular docking and bioinformatics were integrated to explore the mechanism and then the prediction was further supported by experiments. Moreover, both compounds were subjected to ADMET prediction through relevant databases. RESULTS: 28 compounds were isolated from the most bioactive fraction, ethyl acetate extract A. stechmanniana, in which five compounds (abietic acid, oplopanone, oplodiol, hydroxydavanone, linoleic acid) could attenuate mice livers damage caused by alcohol intragastration, reduce the degree of oxidative stress, and serum AST and ALT, respectively. Furthermore, abietic acid and hydroxydavanone exhibited best protective effect against alcohol-stimulated L-O2 cells injury among five bioactive compounds. Network pharmacology and bioinformatics analysis suggested that abietic acid and hydroxydavanone exhibiting drug likeliness characteristics, were the principal active compounds acting on liver injury treatment, primarily impacting to cell proliferation, oxidative stress and inflammation-related PI3K-AKT signaling pathways. Both of them displayed strong binding energies with five target proteins (HRAS, HSP90AA1, AKT1, CDK2, NF-κB p65) via molecular docking. Western blotting results further supported the predication with up-regulation of protein expressions of CDK2, and down-regulation of HRAS, HSP90AA1, AKT1, NF-κB p65 by abietic acid and hydroxydavanone. CONCLUSION: Alcohol-induced liver injury protection by A. stechmanniana was verified in vivo and in vitro expanded its traditional use, and its two major bioactive compounds, abietic acid and hydroxydavanone exerted hepatoprotective effect through the regulation of PI3K-AKT signaling pathway.

Formononetin Derivative for Osteoporosis by Simultaneous Regulating Osteoblast and Osteoclast.

Seven new formononetin derivatives (1-7) were designed and prepared from formononetin (phase II phytoestrogen). The derivatives 9-butyl-3-(4-methoxyphenyl)-9,10-dihydro-4H,8H-chromeno[8,7-e][1,3]oxazin-4-one (2) and 9-(furan-3-ylmethyl)-3-(4-methoxyphenyl)-9,10-dihydro-4H,8H-chromeno[8,7-e][1,3]oxazin-4-one (7) promoted significant osteoblast formation by modulating the BMP/Smad pathway. Compound 7 exhibited potent antiosteoclastogenesis activity in RANKL-induced RAW264.7 cells and ovariectomy (OVX)-induced osteoporosis in mice by regulation of the RANK/RANKL/OPG pathway. Compound 7 regulated osteoblast and osteoclast simultaneously and showed better effect than the well-known drug ipriflavone in vivo, suggesting 7 as a patented antiosteoporosis candidate.

Advances in attenuating opioid-induced respiratory depression: A narrative review.

Opioids exert analgesic effects by agonizing opioid receptors and activating signaling pathways coupled to receptors such as G-protein and/or ß-arrestin. Concomitant respiratory depression (RD) is a common clinical problem, and improvement of RD is usually achieved with specific antagonists such as naloxone; however, naloxone antagonizes opioid analgesia and may produce more unknown adverse effects. In recent years, researchers have used various methods to isolate opioid receptor-mediated analgesia and RD, with the aim of preserving opioid analgesia while attenuating RD. At present, the focus is mainly on the development of new opioids with weak respiratory inhibition or the use of non-opioid drugs to stimulate breathing. This review reports recent advances in novel opioid agents, such as mixed opioid receptor agonists, peripheral selective opioid receptor agonists, opioid receptor splice variant agonists, biased opioid receptor agonists, and allosteric modulators of opioid receptors, as well as in non-opioid agents, such as AMPA receptor modulators, 5-hydroxytryptamine receptor agonists, phosphodiesterase-4 inhibitors, and nicotinic acetylcholine receptor agonists.

Root-to-shoot signaling positively mediates source-sink relation in late growth stages in diploid and tetraploid wheat.

Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

Novel role of NCoR1 in impairing spatial memory through the mediation of a novel interacting protein DEC2.

Long-term memory formation requires de novo RNA and protein synthesis. Using differential display PCR, we found that the NCoR1 cDNA fragment is differentially expressed between fast learners and slow learners, with fast learners showing a lower expression level than slow learners in the water maze learning task. Fast learners also show lower NCoR1 mRNA and protein expression levels. In addition, spatial training decreases both NCoR1 mRNA and protein expression, whereas NCoR1 conditional knockout (cKO) mice show enhanced spatial memory. In studying the molecular mechanism, we found that spatial training decreases the association between NCoR1 and DEC2. Both NCoR1 and DEC2 suppress the expression of BDNF, integrin α3 and SGK1 through C/EBPα binding to their DNA promoters, but overexpression of DEC2 in NCoR1 cKO mice rescues the decreased expression of these proteins compared with NCoR1 loxP mice overexpressing DEC2. Further, spatial training decreases DEC2 expression. Spatial training also enhances C/EBPα binding to Bdnf, Itga3 and Sgk1 promoters, an effect also observed in fast learners, and both NCoR1 and DEC2 control C/EBPα activity. Whereas knockdown of BDNF, integrin α3 or SGK1 expression impairs spatial learning and memory, it does not affect Y-maze performance, suggesting that BDNF, integrin α3 and SGK1 are involved in long-term memory formation, but not short-term memory formation. Moreover, NCoR1 expression is regulated by the JNK/c-Jun signaling pathway. Collectively, our findings identify DEC2 as a novel interacting protein of NCoR1 and elucidate the novel roles and mechanisms of NCoR1 and DEC2 in negative regulation of spatial memory formation.

Revision of the Genus Rhagastis Rothschild & Jordan, 1903 (Lepidoptera: Sphingidae) from China, Based on Morphological and Phylogenetic Analyses.

Here, the taxonomy of the genus Rhagastis Rothschild & Jordan, 1903 (Lepidoptera, Sphingidae, Macroglossinae, Macroglossini) from China is revised based on differences in wing morphology, male and female genitalia, and the phylogenetic relationship of the DNA barcodes. Subspecies of Rhagastis albomarginatus (Rothschild, 1894) and R. castor (Walker, 1856) are treated as "good" species, namely Rhagastis dichroae Mell, 1922 stat. nov.; R. everetti Rothschild & Jordan, 1903 stat. nov.; R. aurifera (Butler, 1875) stat. rev.; R. chinensis Mell, 1922 stat. nov.; R. formosana Clark, 1925 stat. nov.; and R. jordani Oberthür, 1904 stat. rev. The distribution maps, biological notes, and ecological records of the genus Rhagastis Rothschild & Jordan, 1903 from China are given, and a species inventory of genus Rhagastis in the world is also included.

Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis decumbens (Thunb.) Pers. was used as stasis-eliminating medicine traditionally to treat cardiovascular disease potentially attributed to its antithrombotic effect, but lack of pharmacological research on it. AIM OF THE STUDY: To investigate the antithrombotic effect of C. decumbens and its preliminary mechanism. MATERIALS AND METHODS: A carrageenan-induced mouse thrombus model and adenosine diphosphate stimulated platelet aggregation of rabbits were used to confirm the inhibitory effect of C. decumbens extract and compounds on thrombosis in vivo. Then, H2O2-induced human umbilical vein endothelial cells (HUVECs) injury model was further adopted to verify the effects of bioactive compounds in vitro. Moreover, in silico network pharmacology analyses and molecular docking were performed to predict the underlying mechanisms, targets, and pathways, and which were further confirmed through western blotting assay. RESULTS: The administration of total extract (TE), total alkaloids (TA) and tetrahydropalmatine (TET) resulted in a significant reduction in black tail thrombus and congestion, along with a decreasing in platelet aggregation of rabbits. A superior antithrombotic effect indicated the bioactive fraction, and then the isolated bioactive compounds, TET and protopine (PRO) increased cell survival, and decreased reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release in H2O2-induced HUVECs injury model. Moreover, the two alkaloids targeted 33 major proteins and influenced 153 pathways in network pharmacology prediction. Among these, HSP90AA1, COX-2, NF-κB/p65, MMP1 and HIF-1α were the key proteins and PI3K-Akt emerged as the major signaling pathway. Further western blotting results supported that five key proteins were downregulated by the two bioactive compounds in H2O2-stimulated HUVECs model. CONCLUSION: C. decumbens exerted protective effect on thrombosis through inhibiting PI3K-Akt pathway and related key proteins, which supported the traditional use and presented potential antithrombotic alkaloids for further investigation.

Development of an on-site diagnostic LAMP assay for rapid differentiation of the invasive pest Phthorimaea absoluta (Meyrick) using insect tissues.

BACKGROUND: The tomato leafminer, Phthorimaea absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a destructive invasive pest that originated in South America and has spread within China since 2017. A rapid method for on-site identification of P. absoluta is urgently needed for interception of this pest across China. RESULTS: We developed a loop-mediated isothermal amplification (LAMP) technique to differentiate P. absoluta from Liriomyza sativae, Chromatomyia horticola, and Phthorimaea operculella using extracted genomic DNA, which was then refined to create an on-site LAMP diagnostic method that can be performed under field conditions without the need for laboratory equipment. CONCLUSION: In the present research, we developed an on-site diagnostic method for rapid differentiation of P. absoluta from other insects with similar morphology or damage characteristics in China. © 2024 Society of Chemical Industry.

Efficacy of metastatic lesion radiotherapy in patients with metastatic nasopharyngeal carcinoma: A multicenter retrospective study.

OBJECTIVE: We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). MATERIALS AND METHODS: Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. RESULTS: We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. CONCLUSIONS: MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes.

Unveilling genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance in Staphylococcus aureus isolated from a Malaysian Teaching Hospital.

BACKGROUND: Staphylococcus aureus is a notorious multidrug resistant pathogen prevalent in healthcare facilities worldwide. Unveiling the mechanisms underlying biofilm formation, quorum sensing and antibiotic resistance can help in developing more effective therapy for S. aureus infection. There is a scarcity of literature addressing the genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance among S. aureus isolates from Malaysia. METHODS: Biofilm and slime production of 68 methicillin-susceptible S. aureus (MSSA) and 54 methicillin-resistant (MRSA) isolates were determined using a a plate-based crystal violet assay and Congo Red agar method, respectively. The minimum inhibitory concentration values against 14 antibiotics were determined using VITEK® AST-GP67 cards and interpreted according to CLSI-M100 guidelines. Genetic profiling of 11 S. aureus biofilm-associated genes and agr/sar quorum sensing genes was performed using single or multiplex polymerase chain reaction (PCR) assays. RESULTS: In this study, 75.9% (n = 41) of MRSA and 83.8% (n = 57) of MSSA isolates showed strong biofilm-forming capabilities. Intermediate slime production was detected in approximately 70% of the isolates. Compared to MSSA, significantly higher resistance of clindamycin, erythromycin, and fluoroquinolones was noted among the MRSA isolates. The presence of intracellular adhesion A (icaA) gene was detected in all S. aureus isolates. All MSSA isolates harbored the laminin-binding protein (eno) gene, while all MRSA isolates harbored intracellular adhesion D (icaD), clumping factors A and B (clfA and clfB) genes. The presence of agrI and elastin-binding protein (ebpS) genes was significantly associated with biofilm production in MSSA and MRSA isolates, respectively. In addition, agrI gene was also significantly correlated with oxacillin, cefoxitin, and fluoroquinolone resistance. CONCLUSIONS: The high prevalence of biofilm and slime production among MSSA and MRSA isolates correlates well with the detection of a high prevalence of biofilm-associated genes and agr quorum sensing system. A significant association of agrI gene was found with cefoxitin, oxacillin, and fluoroquinolone resistance. A more focused approach targeting biofilm-associated and quorum sensing genes is important in developing new surveillance and treatment strategies against S. aureus biofilm infection.

Structure optimizing of flavonoids against both MRSA and VRE.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 µg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.