Development of a novel membrane-based quorum-quenching microbial isolator for biofouling control: Process performance and microbial mechanism.

Quorum quenching (QQ) can mitigate biofouling in membrane bioreactors (MBRs) by inhibiting cell-to-cell communication. However, it is difficult to maintain long-term QQ activity. Here, a novel microbial isolator composed of tubular microfiltration membranes was developed to separate QQ bacteria (Rhodococcus sp. BH4) from sludge. The time to reach a transmembrane pressure of 50 kPa was delayed by 69.55 % (p = 0.002, Student's t test) in MBR with QQ microbial isolator (MBR-Q), compared to that in the control MBR (MBR-C) during stable operation. The concentration of proteins in the extracellular polymeric substances of sludge was reduced by 20.61 % in MBR-Q relative to MBR-C. The results of the bacterial community analyses indicated less enrichment of fouling-associated bacteria (e.g., Acinetobacter) but a higher abundance of QQ enzymes in MBR-Q than in MBR-C. This environmentally friendly technique can decrease the cleaning frequency and increase the membrane lifespan, thus improving the sustainability of MBR technology.

Analysis the molecular similarity of least common amino acid sites in ACE2 receptor to predict the potential susceptible species for SARS-CoV-2.

SARS-CoV-2 infections in animals have been reported globally. However, the understanding of the complete spectrum of animals susceptible to SARS-CoV-2 remains limited. The virus's dynamic nature and its potential to infect a wide range of animals are crucial considerations for a One Health approach that integrates both human and animal health. This study introduces a bioinformatic approach to predict potential susceptibility to SARS-CoV-2 in both domestic and wild animals. By examining genomic sequencing, we establish phylogenetic relationships between the virus and its potential hosts. We focus on the interaction between the SARS-CoV-2 genome sequence and specific regions of the host species' ACE2 receptor. We analyzed and compared ACE2 receptor sequences from 29 species known to be infected, selecting 10 least common amino acid sites (LCAS) from key binding domains based on similarity patterns. Our analysis included 49 species across primates, carnivores, rodents, and artiodactyls, revealing complete consistency in the LCAS and identifying them as potentially susceptible. We employed the LCAS similarity pattern to predict the likelihood of SARS-CoV-2 infection in unexamined species. This method serves as a valuable screening tool for assessing infection risks in domestic and wild animals, aiding in the prevention of disease outbreaks.

Micro- and Mesoporous Structural Effects of Beta Zeolites for Volatile Organic Compound Sorption.

To fully exploit pore engineering in the design of more efficient zeolite adsorbents for volatile organic compound (VOC) treatment, the roles of meso- and micropores need to be clarified to provide the theoretical basis and feasible measures. In this work, the three VOC sorption properties of conventional and hierarchical porous beta zeolites were comparatively investigated to study the roles of meso- and micropores. There is a division of functions between micro- and mesopores, with micropores being the main VOC adsorption sites and mesopores greatly enhancing VOC diffusion and adsorbent reusability. On the one hand, micropores should be preserved as much as possible because obtaining mesopores by sacrificing micropores (i.e., alkali treatment) results in 28-60% decreases in adsorption capacities. On the other hand, mesopore introduction is highly desirable, which results in an enhancement of VOC intraparticle diffusion rates by 1.3-2.3 times (at the VOC concentration of 600 ppm) and chlorobenzene adsorption capacity on the 20th cycle increasing from 78% of the initial value to 89 and 93%. The findings may provide valuable information about zeolite-based adsorbents for adsorption removal or recovery of VOCs.

Study on the Mechanical Properties of a Carbon-Fiber/Glass-Fiber Hybrid Foam Sandwich Structure.

Considering the different structural strength requirements of different parts of fiberglass yachts, carbon fiber/glass fiber hybrid reinforcement can be applied to the skins of sandwich panels in special areas. This paper designs and prepares 12 foam sandwich panel samples composed of pure carbon fiber, a carbon fiber/glass fiber hybrid, pure glass fiber skin, and PVC and SAN foam sandwich, with reference to the layup structure of the outer panel of a fiberglass yacht. Through a comparative analysis of low-speed impact experiments, edge compression experiments, and short beam three-point bending experiments, we seek the optimal carbon fiber/glass fiber hybrid layup design scheme for local structures to guide production. The results show that a reasonable hybrid carbon fiber layup in fiberglass skin can effectively reduce the low-speed impact damage of the sandwich structure, reduce edge compression damage, and improve the bending and compression resistance of sandwich structure. The impact resistance, compression resistance, and shear resistance of the SAN sandwich structure are stronger than the PVC sandwich structure. The carbon fiber/glass fiber hybrid SAN foam sandwich structure can be used for the local structural reinforcement of special parts such as the bow, side, and main deck of fiberglass yachts.

Tolypocladium sinense Mycelium Polysaccharide Alleviates Obesity, Lipid Metabolism Disorder, and Inflammation Caused by High Fat Diet via Improving Intestinal Barrier and Modulating Gut Microbiota.

SCOPE: Tolypocladium sinense is a fungus isolated from Cordyceps. Cordyceps has some medicinal value and is also a daily health care product. This study explores the preventive effects of T. sinense mycelium polysaccharide (TSMP) on high-fat diet-induced obesity and chronic inflammation in mice. METHODS AND RESULTS: Here, the study establishes an obese mouse model induced by high-fat diet. In this study, the mice are administered TSMP daily basis to evaluate its effect on alleviating obesity. The results show that TSMP can significantly inhibit obesity and alleviate dyslipidemia by regulating the expression of lipid metabolism-related genes such as liver kinase B1 (LKB1), phosphorylated AMP-activated protein kinase (pAMPK), peroxisome proliferator activated receptor α (PPARα), fatty acid synthase (FAS), and hydroxymethylglutaryl-CoA reductase (HMGCR) in the liver. TSMP can increase the protein expression of zona occludens-1 (ZO-1), Occludin, and Claudin-1 in the colon, improve the intestinal barrier dysfunction, and reduce the level of serum LPS, thereby reducing the inflammatory response. 16S rDNA sequencing shows that TSMP alters the intestinal microbiota by increasing the relative abundance of Akkermansia, Lactobacillus, and Prevotellaceae_NK3B31_group, while decreasing the relative abundance of Faecalibaculum. CONCLUSION: The findings show that TSMP can inhibit obesity and alleviates obesity-related lipid metabolism disorders, inflammatory responses, and oxidative stress by modulating the gut microbiota and improving intestinal barrier.

Voacangine protects hippocampal neuronal cells against oxygen-glucose deprivation/reoxygenation-caused oxidative stress and ferroptosis by activating the PI3K-Akt-FoxO signaling.

Voacangine, a naturally occurring alkaloid, has been testified to display beneficial effects on a variety of human diseases, but its role in ischemic stroke is unclear. The impacts of voacangine on oxygen-glucose deprivation/reoxygenation (OGD/R)-tempted hippocampal neuronal cells are investigated. The bioinformatics analysis found that voacangine is a bioactive ingredient that may have good effects on ischemic stroke. KEGG pathways analysis found that voacangine may regulate ischemic stroke through modulating the PI3K-Akt-FoxO signaling pathway. Voacangine could mitigate OGD/R-tempted cytotoxicity in HT22 cells. Voacangine mitigated OGD/R-tempted oxidative stress in HT22 cells by diminishing reactive oxygen species level and enhancing superoxide dismutase level. Voacangine mitigated OGD/R-tempted ferroptosis in HT22 cells. Voacangine promoted activation of the PI3K-Akt-FoxO signaling in OGD/R-induced HT22 cells. Inactivation of the PI3K-Akt-FoxO signaling pathway reversed the protective effects of voacangine against OGD/R-tempted oxidative stress, cytotoxicity, and ferroptosis in HT22 cells. In conclusion, voacangine protects hippocampal neuronal cells against OGD/R-caused oxidative stress and ferroptosis by activating the PI3K-Akt-FoxO signaling.

Enterococcus durans 98D alters gut microbial composition and function to improve DSS-induced colitis in mice.

Enterococcus durans, is a potential functional strain with the capacity to regulate intestinal health and ameliorate colonic inflammation. However, the strain requires further investigation regarding its safety profile and potential mechanisms of colitis improvement. In this study, the safety of E. durans 98D (Ed) as a potential probiotic was studied using in vitro methods. Additionally, a dextran sulfate sodium (DSS)-induced murine colitis model was employed to investigate its impact on the intestinal microbiota and colitis. In vitro antimicrobial assays revealed Ed sensitivity to common antibiotics and its inhibitory effect on the growth of Escherichia coli O157, Streptococcus pneumoniae CCUG 37328, and Staphylococcus aureus ATCC 25923. To elucidate the functional properties of Ed, 24 weight-matched 6-week-old female C57BL/6J mice were randomly divided into three groups (n = 8): NC group, Con group (DSS), and Ed group (DSS + Ed). Ed administration demonstrated a protective effect on colitis mice, as evidenced by improvements in body weight, colonic length, reduced disease activity index, histological scores, diminished splenomegaly, and decreased goblet cell loss. Furthermore, Ed downregulated the expression of the pro-inflammatory cytokine genes (IL-6, IL-1ß, and TNF-α) and upregulated the expression of the anti-inflammatory cytokine gene IL-10. The 16S rRNA gene sequencing revealed significant alterations in microbial α-diversity, with principal coordinate analysis indicating distinct differences in microbial composition among the three groups. At the phylum level, the relative abundance of Actinomycetota significantly increased in the Ed-treated group. At the genus level, Ed treatment markedly elevated the relative abundance of Paraprevotella, Rikenellaceae_RC9, and Odoribacter in DSS-induced colitis mice. In conclusion, Ed exhibits potential as a safe and effective therapeutic agent for DSS-induced colitis by reshaping the colonic microbiota.

Multiple hydrogen-bonding induced nonconventional red fluorescence emission in hydrogels.

The development of unconventional long-wavelength fluorescent polymer hydrogels without using polycyclic aromatic hydrocarbons or extended π-conjugation is a fundamental challenge in luminescent materials owing to a lack of understanding regarding the spatial interactions induced inherent clustering-triggered emission under water-rich conditions. Inspired by the color change of protein astaxanthin as a result of heat-induced denaturation, we propose a thermodynamically driven strategy to develop red fluorescence (~610 nm) by boiling multiple hydrogen-bonded poly(N-acryloylsemicarbazide) hydrogels in a water bath. We reveal that thermodynamically driven conformational changes of polymer chains from isolated hydrogen bonding donor-acceptor structures to through-space interaction structures induce intrinsic fluorescence shifts from blue to red during clustering-triggered emission. The proposed multiple hydrogen-bonding supramolecular hydrogel shows good fluorescence stability, mechanical robustness, and 3D printability for customizable shaping. We provide a viable method to prepare nonconventional long-wavelength fluorescent hydrogels towards soft fluorescent devices without initially introducing any fluorescent components.

Plasma Metabolic Profiling and Multiclass Diagnostic Model Development for Stable Angina Pectoris and Acute Myocardial Infarction.

Coronary heart disease remains a major global health challenge, with a clear need for enhanced early risk assessment. This study aimed to elucidate metabolic signatures across various stages of coronary heart disease and develop an effective multiclass diagnostic model. Using metabolomic approaches, gas chromatography-mass and liquid chromatography-tandem mass spectrometry were used to analyze plasma samples from healthy controls, patients with stable angina pectoris, and those with acute myocardial infarction. Pathway enrichment analysis was conducted on metabolites exhibiting significant differences. The key metabolites were identified using Random Forest and Recursive Feature Elimination strategies to construct a multiclass diagnostic model. The performance of the model was validated through 10-fold cross-validation and evaluated using confusion matrices, receiver operating characteristic curves, and calibration curves. Metabolomics was used to identify 1491 metabolites, with 216, 567, and 295 distinctly present among the healthy controls, patients with stable angina pectoris, and those with acute myocardial infarction, respectively. This implicated pathways such as the glucagon signaling pathway, d-amino acid metabolism, pyruvate metabolism, and amoebiasis across various stages of coronary heart disease. After selection, testosterone isobutyrate, N-acetyl-tryptophan, d-fructose, l-glutamic acid, erythritol, and gluconic acid were identified as core metabolites in the multiclass diagnostic model. Evaluating the diagnostic model demonstrated its high discriminative ability and accuracy. This study revealed metabolic pathway perturbations at different stages of coronary heart disease, and a precise multiclass diagnostic model was established based on these findings. This study provides new insights and tools for the early diagnosis and treatment of coronary heart disease.

Huanglian Jiedu decoction inhibits vascular smooth muscle cell-derived foam cell formation by activating autophagy via suppressing P2RY12.

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu Decoction (HLJDD) is a Chinese medicine with a long history of therapeutic application. It is widely used in treating atherosclerosis (AS) in Chinese medicine theory and clinical practice. However, the mechanism of HLJDD in treating AS remains unclear. AIM OF THE STUDY: To investigate the efficacy and mechanism of HLJDD in treating AS. MATERIALS AND METHODS: AS was induced on high-fat diet-fed ApoE-/- mice, with the aorta pathological changes evaluated with lipid content and plaque progression. In vitro, foam cells were induced by subjecting primary mouse aortic vascular smooth muscle cells (VSMCs) to oxLDL incubation. After HLJDD intervention, VSMCs were assessed with lipid stack, apoptosis, oxidative stress, and the expression of foam cell markers. The effects of P2RY12 were tested by adopting clopidogrel hydrogen sulfate (CDL) in vivo and transfecting P2RY12 over-expressive plasmid in vitro. Autophagy was inhibited by Chloroquine or transfecting siRNA targeting ATG7 (siATG7). The mechanism of HLJDD treating atherosclerosis was explored using network pharmacology and validated with molecular docking and co-immunoprecipitation. RESULTS: HLJDD exhibited a dose-dependent reduction in lipid deposition, collagen loss, and necrosis within plaques. It also reversed lipid accumulation and down-regulated the expression of foam cell markers. P2RY12 inhibition alleviated AS, while P2RY12 overexpression enhanced foam cell formation and blocked the therapeutic effects of HLJDD. Network pharmacological analysis suggested that HLJDD might mediate PI3K/AKT signaling pathway-induced autophagy. P2RY12 overexpression also impaired autophagy. Similarly, inhibiting autophagy counteracted the effect of CDL, exacerbated AS in vivo, and promoted foam cell formation in vitro. However, HLJDD treatment mitigated these detrimental effects by suppressing the PI3K/AKT signaling pathway. Immunofluorescence and molecular docking revealed a high affinity between P2RY12 and PIK3CB, while co-immunoprecipitation assays illustrated their interaction. CONCLUSIONS: HLJDD inhibited AS in vivo and foam cell formation in vitro by restoring P2RY12/PI3K/AKT signaling pathway-suppressed autophagy. This study is the first to reveal an interaction between P2RY12 and PI3K3CB.

Geniposide ameliorates atherosclerosis by restoring lipophagy via suppressing PARP1/PI3K/AKT signaling pathway.

BACKGROUND: Atherosclerosis (AS) is the leading cause of global death, which manifests as arterial lipid stack and plaque formation. Geniposide is an iridoid glycoside extract from Gardenia jasminoides J.Ellis that ameliorates AS by mediating autophagy. However, how Geniposide regulates autophagy and treats AS remains unclear. PURPOSE: To evaluate the efficacy and mechanism of Geniposide in treating AS. STUDY DESIGN AND METHODS: Geniposide was administered to high-fat diet-fed ApoE-/- mice and oxidized low-density lipoprotein-incubated primary vascular smooth muscle cells (VSMCs). AS was evaluated with arterial lipid stack, plaque progression, and collagen loss in the artery. Foam cell formation was detected by lipid accumulation, inflammation, apoptosis, and the expression of foam cell markers. The mechanism of Geniposide in treating AS was assessed using network pharmacology. Lipophagy was measured by lysosomal activity, expression of lipophagy markers, and the co-localization of lipids and lipophagy markers. The effects of lipophagy were blocked using Chloroquine. The role of PARP1 was assessed by Olaparib (a PARP1 inhibitor) intervention and PARP1 overexpression. RESULTS: In vivo, Geniposide reversed high-fat diet-induced hyperlipidemia, plaque progression, and inflammation. In vitro, Geniposide inhibited VSMC-derived foam cell formation by suppressing lipid stack, apoptosis, and the expressions of foam cell markers. Network pharmacological analysis and in vitro validation suggested that Geniposide treated AS by enhancing lipophagy via suppressing the PI3K/AKT signaling pathway. The benefits of Geniposide in alleviating AS were offset by Chloroquine in vivo and in vitro. Inhibiting PARP1 using Olaparib promoted lipophagy and alleviated AS progression, while PARP1 overexpression exacerbated foam cell formation and lipophagy blockage. The above effects of PARP1 were weakened by PI3K inhibitor LY294002. PARP1 also inhibited the combination of the ABCG1 and PLIN1. CONCLUSION: Geniposide alleviated AS by restoring PARP1/PI3K/AKT signaling pathway-suppressed lipophagy. This study is the first to present the lipophagy-inducing effect of Geniposide and the binding of ABCG1 and PLIN1 inhibited by PARP1.

Blood cellular membrane-coated Au/polydopamine nanoparticle-targeted NIR-II antibacterial therapy.

Bacterial infections are the primary causes of infectious diseases in humans. In recent years, the abuse of antibiotics has led to the widespread enhancement of bacterial resistance. Concerns have been raised about the identification of a common treatment platform for bacterial infections. In this study, a composite nanomaterial was used for near-infrared II (NIR-II) photothermal antibacterial treatment. Red blood cell membrane was peeled and coated onto the surface of the Au/polydopamine nanoparticle-containing aptamer. The composite nanomaterials based on Au/polydopamine exhibit highest photothermal conversion capability. Moreover, these assembled nanoparticles can quickly enter the body's circular system with a specific capability to recognise bacteria. In vivo experiments demonstrated that the composites could kill bacteria from infected blood while significantly reducing the level of bacteria in various organs. Such assemblies offer a paradigm for the treatment of bacterial infections caused by the side effects of antibiotics.

Viral metagenomic analysis reveals diverse viruses and a novel bocaparvovirus in the enteric virome of snow leopard (Panthera uncia).

The enteric virome, comprising a complex community of viruses inhabiting the gastrointestinal tract, plays a significant role in health and disease dynamics. In this study, the fecal sample of a wild snow leopard was subjected to viral metagenomic analysis using a double barcode Illumina MiSeq platform. The resulting reads were de novo assembled into contigs with SOAPdenovo2 version r240. Additional bioinformatic analysis of the assembled genome and genome annotation was done using the Geneious prime software (version 2022.0.2). Following viral metagenomic analysis and bioinformatic analysis, a total of 7 viral families and a novel specie of bocaparvovirus tentatively named Panthera uncia bocaparvovirus (PuBOV) with GenBank accession number OQ627713 were identified. The complete genome of PuBOV was predicted to contain 3 open reading frames (ORFs), contains 5433 nucleotides and has a G + C content of 47.40 %. BLASTx analysis and pairwise sequence comparison indicated the novel virus genome was a new species in the genus Bocaparvovirus based on the species demarcation criteria of the International Committee on the Taxonomy of Viruses. This study provides valuable insights into the diversity and composition of the enteric virome in wild endangered snow leopards. The identification and characterization of viruses in wildlife is crucial for developing effective strategies to manage and mitigate potential zoonotic and other viral disease threats to human and animal health.

A new method to analysis synthetic acetic acid to vinegar: Hydrogen isotope ratio at the methyl site of acetic acid in vinegar by GC-IRMS.

Acetic acid is the key organic substance used to verify the authenticity of vinegar. A new method for precisely determining acetic acid δDCH3 in vinegar via gas chromatography -pyrolytic-stable isotope ratio mass spectrometry (GC-P-IRMS) was established. The δDCH3 values were obtained via calibration with a series of standards. The optimised method demonstrated a repeatability standard deviation within 3 ‰. The standard deviation of accuracy of the new method compared with that of the SNIF-NMR method was within 2.6 ‰. The synthetic acetic acid δDCH3 values was -136.7 ‰ ± 29.6 ‰, and the δDCH3 value of acetic acid in vinegar was -414.9 ‰ ± 40.5 ‰, with significant isotopic distribution characteristics. This methodology serves as a supplementary method for measuring the δDCH3 value of acetic acid in vinegar. It has advantages over other methods in terms of time, sensitivity and operability. And provides a new idea for solving the problem of analyzing substances in the presence of exchangeable groups.

The role of DNA and RNA guanosine oxidation in cardiovascular diseases.

Cardiovascular diseases (CVD) persist as a prominent cause of mortality worldwide, with oxidative stress constituting a pivotal contributory element. The oxidative modification of guanosine, specifically 8-oxoguanine, has emerged as a crucial biomarker for oxidative stress, providing novel insights into the molecular underpinnings of CVD. 8-Oxoguanine can be directly generated at the DNA (8-oxo-dG) and RNA (8-oxo-G) levels, as well as at the free nucleotide level (8-oxo-dGTP or 8-oxo-GTP), which are produced and can be integrated through DNA replication or RNA transcription. When exposed to oxidative stress, guanine is more readily produced in RNA than in DNA. A burgeoning body of research surrounds 8-oxoguanine, exhibits its accumulation playing a pivotal role in the development of CVD. Therapeutic approaches targeting oxidative 8-Oxoguanine damage to DNA and RNA, encompassing the modulation of repair enzymes and the development of small molecule inhibitors, are anticipated to enhance CVD management. In conclusion, we explore the noteworthy elevation of 8-oxoguanine levels in patients with various cardiac conditions and deliberate upon the formation and regulation of 8-oxo-dG and 8-oxo-G under oxidative stress, as well as their function in CVD.

Actively extracting kidney stones combined dusting technique can improve SFR of moderate-complexity kidney stones in fURL.

PURPOSE: To evaluate the necessity and effectiveness of actively extracting kidney stones with different complexity that have been visually dusted in flexible ureteroscopic lithotripsy (fURL). METHODS: We retrospectively reviewed the medical records of patients who underwent fURL with dusting technique in established hospitals. A total of 535 cases were divided into the dusting group or the dusting plus basketing group according to the use of stone basket. Their characteristics and operative parameters were collected and analyzed. We used the R.I.R.S. scoring system to classify the complexity of kidney stones and divided these kidney stones into three subgroups, namely, mild-, moderate-, and severe-complexity group. And then, the effectiveness of stone basket in these subgroups was analyzed. RESULTS: Although using a stone basket significantly reduced re-operation rate (17.8% in dusting group versus 10.2% in dusting plus basketing group, p = 0.013), no significant difference on stone-free rate (SFR) and overall incidence of complications were noticed between groups. After we classified the complexity of kidney stones using the R.I.R.S. scoring system, we found a stone basket was helpful to improve SFR in kidney stones with moderate-complexity that had been visually dusted in fURL (73.5% in dusting group versus 87.3% in dusting plus basketing group, p = 0.002) but had limited influence on SFR in mild (93.8% in dusting group versus 92.6% in dusting plus basketing group, p = 0.783) or severe (28.5% in dusting group versus 34.0% in dusting plus basketing group, p = 0.598)-complexity kidney stones. CONCLUSION: The use of stone basket should be encouraged in moderate-complexity kidney stones which can be visually dusted in fURL.

[Research progress of haematopoietic stem cells to generate immune cells and its application].

Hematopoietic stem cells (HSCs) posses the potential for highly self-renewal, proliferation and multi-lineage differentiation. HSC transplantation has long been the primary method for treating hematologic disorders and autoimmune diseases, and the ability to rebuild the immune system after transplantation is a key indicator of success. To enhance the reconstruction ability of the immune system after transplantation, current research focuses on genetic engineering and the use of HSCs modified by clustered regularly interspaced short palindromic repeats (CRISPR) gene editing technology as a source of transplant cells. This article summaries the biological characteristics, regulatory mechanism, ability to differentiate into immune cells, as well as the application and advance in the treatment of blood disorders, immune deficiencies, cancers and other related diseases, aiming to provide references for the research on relevant diseases.

Regulation of ARGs abundance by biofilm colonization on microplastics under selective pressure of antibiotics in river water environment.

Interactions of microplastics (MPs) biofilm with antibiotic resistance genes (ARGs) and antibiotics in aquatic environments have made microplastic biofilm an issue of keen scholarly interest. The process of biofilm formation and the degree of ARGs enrichment in the presence of antibiotic-selective pressure and the impact on the microbial community need to be further investigated. In this paper, the selective pressure of ciprofloxacin (CIP) and illumination conditions were investigated to affect the physicochemical properties, biomass, and extracellular polymer secretion of polyvinyl chloride (PVC) microplastic biofilm. In addition, relative copy numbers of nine ARGs were analyzed by real-time quantitative polymerase chain reaction (qPCR). In the presence of CIP, microorganisms in the water and microplastic biofilm were more inclined to carry associated ARGs (2-3 times higher), which had a contributing effect on ARGs enrichment. The process of pre-microplastic biofilm formation might have an inhibitory effect on ARGs (total relative abundance up to 0.151) transfer and proliferation compared to the surrounding water (total relative abundance up to 0.488). However, in the presence of CIP stress, microplastic biofilm maintained the abundance of ARGs (from 0.151 to 0.149) better compared to the surrounding water (from 0.488 to 0.386). Therefore, microplastic biofilm act as abundance buffer island of ARGs stabilizing the concentration of ARGs. In addition, high-throughput analyses showed the presence of antibiotic-resistant (Pseudomonas) and pathogenic (Vibrio) microorganisms in biofilm under different conditions. The above research deepens our understanding of ARGs enrichment in biofilm and provides important insights into the ecological risks of interactions between ARGs, antibiotics, and microplastic biofilm.

Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging.

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.