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.

Zinc-Catalyzed Enantioselective Formal (3+2) Cycloadditions of Bicyclobutanes with Imines: Catalytic Asymmetric Synthesis of Azabicyclo[2.1.1]hexanes.

The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp3)-rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza-BCHs) by an enantioselective zinc-catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2-acyl imidazole group and a diverse array of alkynyl- and aryl-substituted imines. The target aza-BCHs, which consist of α-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94% yield and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring-opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid-catalyzed cycloadditions of BCBs.

The gut microbiota improves reproductive dysfunction in obese mice by suppressing the NLRP3/ASC/caspase-1 axis.

Aim: To explore the complex relationship between gut microbiota, obesity-related male reproductive impairments, and the NLRP3 inflammasome.Methods: A high-fat diet was administered to induce obesity in a mouse model, fecal microbiota transplantation or a high-dietary fiber diet (HDFD) was administered for 5 weeks to evaluate changes in parameters related to reproductive capacity, NLRP3, gut microbiota composition and metabolites in mice.Results: A high-fat diet induces obesity and decreases reproductive capacity in male mice. Fecal microbiota transplantation and HDFD can improve reproductive capacity in obese mice by adjusting the gut microbiota population to suppress the NLRP3/ASC/caspase-1 axis, thereby reducing IL-1ß levels.Conclusion: This study offers a potential treatment for obesity-induced reproductive dysfunction by targeting the gut microbiota and the NLRP3 inflammasome pathway.

This study looks at how gut bacteria, obesity and our immune system affect male reproductive health. We made mice obese by feeding them a high-fat diet. Then, we treated them with either a transplant of gut bacteria or a high-fiber diet for 5 weeks. We found that the high-fat diet made it harder for male mice to have babies. Both the transplant and the high-fiber diet helped improve their ability to reproduce. Changing the bacteria in their gut reduced inflammation by affecting the immune system. Our findings suggest that changing gut bacteria and focusing on this part of the immune system could help with reproductive problems caused by obesity.

Enantioselective formal (3 + 3) cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis.

The absence of catalytic asymmetric methods for synthesizing chiral (hetero)bicyclo[n.1.1]alkanes has hindered their application in new drug discovery. Here we demonstrate the achievability of an asymmetric polar cycloaddition of bicyclo[1.1.0]butane using a chiral Lewis acid catalyst and a bidentate chelating bicyclo[1.1.0]butane substrate, as exemplified by the current enantioselective formal (3 + 3) cycloaddition of bicyclo[1.1.0]butanes with nitrones. In addition to the diverse bicyclo[1.1.0]butanes incorporating an acyl imidazole group or an acyl pyrazole moiety, a wide array of nitrones are compatible with this Lewis acid catalysis, successfully assembling two congested quaternary carbon centers and a chiral aza-trisubstituted carbon center in the pharmaceutically important hetero-bicyclo[3.1.1]heptane product with up to 99% yield and >99% ee.

Reagent-free anti-fouling electrochemical immunosensor based on AL-BSA/AuNPs/PANI coating for the point-of-care detection of C-reactive protein in plasma and whole blood.

Developing the portable CRP detection technologies that are suitable for point-of-care (POC) and primary care management is of utmost importance, and advancing the electrochemical immunosensors hold promise for POC implementation. Nevertheless, non-specific adsorption of numerous interfering proteins in complex biological media contaminates immunosensors, thereby restricting the reliability in detection efficacy. In this study, a three-dimensional flower-leaf shape amyloid bovine serum albumin/gold nanoparticles/polyaniline (AL-BSA/AuNPs/PANI) coating on the surface of the electrode was developed, which demonstrated strong anti-adsorption properties against bovine serum albumin, plasma, and cells. The immunosensor exhibited a good linear relationship to CRP response, featuring a detection limit of 0.09 µg/mL, consistent with clinical reference range. In addition, the CRP immunosensor demonstrated excellent specificity in other inflammation-related proteins and commendable anti-interference performance for CRP detection in plasma and whole blood tests. Importantly, by combining the development of a USB flash disk-type portable electrochemical workstation with a reagent-free mode, the developed CRP electrochemical immunosensor delivered ideal results in clinical samples. The anti-fouling performance, sensitivity and specificity of the immunosensor, as well as its flexible test modes in clinical samples, provide important scientific basis for developing POC detection technologies of vital biomarkers in complex biological media.

Epigenetic and transcriptional consequences in the endosperm of chemically induced transposon mobilization in Arabidopsis.

Genomic imprinting, an epigenetic phenomenon leading to parent-of-origin-specific gene expression, has independently evolved in the endosperm of flowering plants and the placenta of mammals-tissues crucial for nurturing embryos. While transposable elements (TEs) frequently colocalize with imprinted genes and are implicated in imprinting establishment, direct investigations of the impact of de novo TE transposition on genomic imprinting remain scarce. In this study, we explored the effects of chemically induced transposition of the Copia element ONSEN on genomic imprinting in Arabidopsis thaliana. Through the combination of chemical TE mobilization and doubled haploid induction, we generated a line with 40 new ONSEN copies. Our findings reveal a preferential targeting of maternally expressed genes (MEGs) for transposition, aligning with the colocalization of H2A.Z and H3K27me3 in MEGs-both previously identified as promoters of ONSEN insertions. Additionally, we demonstrate that chemically-induced DNA hypomethylation induces global transcriptional deregulation in the endosperm, leading to the breakdown of MEG imprinting. This study provides insights into the consequences of chemically induced TE remobilization in the endosperm, revealing that chemically-induced epigenome changes can have long-term consequences on imprinted gene expression.

The cores regulation of paraffin-chitosan phase change microcapsules for constant temperature building.

Phase change materials (PCMs) can store and release latent heat under the designed phased change temperature and have received substantial interest for energy conservation and thermal control purposes. The use of PCMs in the construction of constant temperature buildings can improve the comfortable environment and save more energy. However, the leakage of PCMs during phase change process limits the application of PCMs. In this paper, a series of PCMs microcapsules with controllable core numbers is synthesized with paraffin (37 ℃) as the core and cross-linked chitosan as the wall. The single-core phase-change microcapsules (S-PCM) and multicore phase-change microcapsules (M-PCM) were prepared by adjusting the preparation condition. The latent heat of S-PCM and M-PCM are 61.4 mJ mg-1 and 50.1 mJ mg-1, respectively. The S-PCM and M-PCM display good stability without paraffin leakage. In addition, the composite blocks of gypsum and S-PCM (GSCM) and M-PCM (GMCM) were prepared and the thermoregulatory effection was investigated, where the surface temperature of GSCM was 5-10 ℃ lower than that of pure gypsum block. PCMs may also have broad application space in electronics, cold chain, and other industries.

Switching between the [2π+2σ] and Hetero-[4π+2σ] Cycloaddition Reactivity of Bicyclobutanes with Lewis Acid Catalysts Enables the Synthesis of Spirocycles and Bridged Heterocycles.

The exploration of the complex chemical diversity of bicyclo[n.1.1]alkanes and their use as benzene bioisosteres has garnered significant attention over the past two decades. Regiodivergent syntheses of thiabicyclo[4.1.1]octanes (S-BCOs) and highly substituted bicyclo[2.1.1]hexanes (BCHs) using a Lewis acid-catalyzed formal cycloaddition of bicyclobutanes (BCBs) and 3-benzylideneindoline-2-thione derivatives have been established. The first hetero-(4+3) cycloaddition of BCBs, catalyzed by Zn(OTf)2, was achieved with a broad substrate scope under mild conditions. In contrast, the less electrophilic BCB ester undergoes a Sc(OTf)3-catalyzed [2π+2σ] reaction with 1,1,2-trisubstituted alkenes, yielding BCHs with a spirocyclic quaternary carbon center. Control experiments and preliminary theoretical calculations suggest that the diastereoselective [2π+2σ] product formation may involve a concerted cycloaddition between a zwitterionic intermediate and E-1,1,2-trisubstituted alkenes. Additionally, the hetero-(4+3) cycloaddition may involve a concerted nucleophilic ring-opening mechanism.

Palladium-Catalyzed Ligand-Controlled Switchable Hetero-(5 + 3)/Enantioselective [2σ+2σ] Cycloadditions of Bicyclobutanes with Vinyl Oxiranes.

For nearly 60 years, significant research efforts have been focused on developing strategies for the cycloaddition of bicyclobutanes (BCBs). However, higher-order cycloaddition and catalytic asymmetric cycloaddition of BCBs have been long-standing formidable challenges. Here, we report Pd-catalyzed ligand-controlled, tunable cycloadditions for the divergent synthesis of bridged bicyclic frameworks. The dppb ligand facilitates the formal (5+3) cycloaddition of BCBs and vinyl oxiranes, yielding valuable eight-membered ethers with bridged bicyclic scaffolds in 100% regioselectivity. The Cy-DPEphos ligand promotes selective hetero-[2σ+2σ] cycloadditions to access pharmacologically important 2-oxabicyclo[3.1.1]heptane (O-BCHeps). Furthermore, the corresponding catalytic asymmetric synthesis of O-BCHeps with 94-99% ee has been achieved using chiral (S)-DTBM-Segphos, representing the first catalytic asymmetric cross-dimerization of two strained rings. The obtained O-BCHeps are promising bioisosteres for ortho-substituted benzenes.

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.

Recent Progress on Porous Carbons for Carbon Capture.

High emission of carbon dioxide (CO2) has caused CO2 levels to reach more than 400 ppm in air and led to a serious climate problem. In addition, in confined spaces such as submarines and aircraft, the CO2 concentration increase in the air caused by human respiration also affects human health. In order to protect the environment and human health, the search for high-performance adsorbents for carbon capture from high and low concentration gas is particularly important. Porous carbon materials, possessing the advantages of low cost and renewability, have set off a boom in the research of porous adsorbents, which have the opportunity to be utilized on a large scale for industrial carbon capture in the future. In this review, we summarize the recent research progress of porous carbons for carbon capture from flue gas and directly from air in the last five years, including activated carbon (AC), heteroatom-modified porous carbon, carbon molecular sieves (CMS), and other porous carbon materials, with a focus on the effects of temperature, water content, and gas flow rate of industrial flue gas on the performance of porous carbon adsorbents. We summarize the preparation strategies of various porous carbons and seek environmental friendly porous carbon materials preparation strategies under the premise of improving the CO2 adsorption capacity and selectivity of porous carbon adsorbents. Based on the effects of real industrial flue gas on adsorbents, we provide new ideas and evaluation methods for the development and preparation of porous carbon materials.

The relationship between symptomatic status and aneurysm wall enhancement characteristics of single unruptured intracranial aneurysm.

OBJECTIVE: We aimed to analyze the aneurysm wall enhancement (AWE) characteristics of a single unruptured intracranial aneurysm (UIA) and observe the relationship between the symptoms of a single UIA and the aneurysm wall. METHODS: In our hospital, 85 patients diagnosed with a single UIA using computed tomography angiography (CTA) were retrospectively analyzed. The patients were divided into symptomatic and asymptomatic groups, including 46 asymptomatic and 39 symptomatic aneurysms. High-resolution magnetic resonance imaging of the vascular wall (HR-MR-VWI) was utilized to ascertain the presence, degree, and extent of AWE and thick-wall enhancement. In addition to AWE characteristics, morphological parameters of aneurysms, such as maximal size, shape, height, neck width, aspect ratio (AR), and size ratio (SR), were scanned using CTA. The differences in the parameters of a single UIA between the two groups were compared. An investigation explored the correlation between the symptom status of a single UIA and AWE. RESULTS: We observed a correlation between symptom status and maximal size, height, and neck width for a single UIA, the presence or absence of AWE, and the levels and boundaries of AWE and thick-wall reinforcement. This study found that the AWE range was independently correlated with symptom status in the multivariate regression analysis. CONCLUSION: A larger AWE range was an independent risk factor for the onset of symptoms in a single UIA.

A comprehensive benchmark of graph-based genetic variant genotyping algorithms on plant genomes for creating an accurate ensemble pipeline.

BACKGROUND: Although sequencing technologies have boosted the measurement of the genomic diversity of plant crops, it remains challenging to accurately genotype millions of genetic variants, especially structural variations, with only short reads. In recent years, many graph-based variation genotyping methods have been developed to address this issue and tested for human genomes. However, their performance in plant genomes remains largely elusive. Furthermore, pipelines integrating the advantages of current genotyping methods might be required, considering the different complexity of plant genomes. RESULTS: Here we comprehensively evaluate eight such genotypers in different scenarios in terms of variant type and size, sequencing parameters, genomic context, and complexity, as well as graph size, using both simulated and real data sets from representative plant genomes. Our evaluation reveals that there are still great challenges to applying existing methods to plants, such as excessive repeats and variants or high resource consumption. Therefore, we propose a pipeline called Ensemble Variant Genotyper (EVG) that can achieve better genotyping performance in almost all experimental scenarios and comparably higher genotyping recall and precision even using 5× reads. Furthermore, we demonstrate that EVG is more robust with an increasing number of graphed genomes, especially for insertions and deletions. CONCLUSIONS: Our study will provide new insights into the development and application of graph-based genotyping algorithms. We conclude that EVG provides an accurate, unbiased, and cost-effective way for genotyping both small and large variations and will be potentially used in population-scale genotyping for large, repetitive, and heterozygous plant genomes.

Sexually dimorphic control of affective state processing and empathic behaviors.

Recognizing the affective states of social counterparts and responding appropriately fosters successful social interactions. However, little is known about how the affective states are expressed and perceived and how they influence social decisions. Here, we show that male and female mice emit distinct olfactory cues after experiencing distress. These cues activate distinct neural circuits in the piriform cortex (PiC) and evoke sexually dimorphic empathic behaviors in observers. Specifically, the PiC → PrL pathway is activated in female observers, inducing a social preference for the distressed counterpart. Conversely, the PiC → MeA pathway is activated in male observers, evoking excessive self-grooming behaviors. These pathways originate from non-overlapping PiC neuron populations with distinct gene expression signatures regulated by transcription factors and sex hormones. Our study unveils how internal states of social counterparts are processed through sexually dimorphic mechanisms at the molecular, cellular, and circuit levels and offers insights into the neural mechanisms underpinning sex differences in higher brain functions.

Mutagenesis of Odorant Receptor Coreceptor Orco Reveals the Odorant-Detected Behavior of the Predator Eupeodes corollae.

The successful mating of the hoverfly and the search for prey aphids are of great significance for biological control and are usually mediated by chemical cues. The odorant receptor co-receptor (Orco) genes play a crucial role in the process of insect odor perception. However, the function of Orco in the mating and prey-seeking behaviors of the hoverfly remains relatively unexplored. In this study, we characterized the Orco gene from the hoverfly, Eupeodes corollae, a natural enemy insect. We used the CRISPR/Cas9 technique to knock out the Orco gene of E. corollae, and the EcorOrco-/- homozygous mutant was verified by the genotype analysis. Fluorescence in situ hybridization showed that the antennal ORN of EcorOrco-/- mutant lack Orco staining. Electroantennogram (EAG) results showed that the adult mutant almost lost the electrophysiological response to 15 odorants from three types. The two-way choice assay and the glass Y-tube olfactometer indicated that both the larvae and adults of hoverflies lost their behavioral preference to the aphid alarm pheromone (E)-ß-farnesene (EBF). In addition, the mating assay results showed a significant decrease in the mating rate of males following the knock out of the EcorOrco gene. Although the mating of females was not affected, the amount of eggs being laid and the hatching rate of the eggs were significantly reduced. These results indicated that the EcorOrco gene was not only involved in the detection of semiochemicals in hoverflies but also plays a pivotal role in the development of eggs. In conclusion, our results expand the comprehension of the chemoreceptive mechanisms in the hoverflies and offers valuable insights for the advancement of more sophisticated pest management strategies.

High-quality assembly and methylome of a Tibetan wild tree peony genome (Paeonia ludlowii) reveal the evolution of giant genome architecture.

Tree peony belongs to one of the Saxifragales families, Paeoniaceae. It is one of the most famous ornamental plants, and is also a promising woody oil plant. Although two Paeoniaceae genomes have been released, their assembly qualities are still to be improved. Additionally, more genomes from wild peonies are needed to accelerate genomic-assisted breeding. Here we assemble a high-quality and chromosome-scale 10.3-Gb genome of a wild Tibetan tree peony, Paeonia ludlowii, which features substantial sequence divergence, including around 75% specific sequences and gene-level differentials compared with other peony genomes. Our phylogenetic analyses suggest that Saxifragales and Vitales are sister taxa and, together with rosids, they are the sister taxon to asterids. The P. ludlowii genome is characterized by frequent chromosome reductions, centromere rearrangements, broadly distributed heterochromatin, and recent continuous bursts of transposable element (TE) movement in peony, although it lacks recent whole-genome duplication. These recent TE bursts appeared during the uplift and glacial period of the Qinghai-Tibet Plateau, perhaps contributing to adaptation to rapid climate changes. Further integrated analyses with methylome data revealed that genome expansion in peony might be dynamically affected by complex interactions among TE proliferation, TE removal, and DNA methylation silencing. Such interactions also impact numerous recently duplicated genes, particularly those related to oil biosynthesis and flower traits. This genome resource will not only provide the genomic basis for tree peony breeding but also shed light on the study of the evolution of huge genome structures as well as their protein-coding genes.

Does dual-layer spectral detector CT provide added value in predicting spread through air spaces in lung adenocarcinoma? A preliminary study.

OBJECTIVES: To examine the predictive value of dual-layer spectral detector CT (DLCT) for spread through air spaces (STAS) in clinical lung adenocarcinoma. METHODS: A total of 225 lung adenocarcinoma cases were retrospectively reviewed for demographic, clinical, pathological, traditional CT, and spectral parameters. Multivariable logistic regression analysis was carried out based on three logistic models, including a model using traditional CT features (traditional model), a model using spectral parameters (spectral model), and an integrated model combining traditional CT and spectral parameters (integrated model). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to assess these models. RESULTS: Univariable analysis showed significant differences between the STAS and non-STAS groups in traditional CT features, including nodule density (p < 0.001), pleural indentation types (p = 0.006), air-bronchogram sign (p = 0.031), the presence of spiculation (p < 0.001), long-axis diameter of the entire nodule (LD) (p < 0.001), and consolidation/tumor ratio (CTR) (p < 0.001). Multivariable analysis revealed that LD > 20 mm (odds ratio [OR] = 2.271, p = 0.025) and CTR (OR = 24.208, p < 0.001) were independent predictors in the traditional model, while electronic density (ED) in the venous phase was an independent predictor in the spectral (OR = 1.062, p < 0.001) and integrated (OR = 1.055, p < 0.001) models. The area under the curve (AUC) for the integrated model (0.84) was the highest (spectral model, 0.83; traditional model, 0.80), and the difference between the integrated and traditional models was statistically significant (p = 0.015). DCA showed that the integrated model had superior clinical value versus the traditional model. CONCLUSIONS: DLCT has added value for STAS prediction in lung adenocarcinoma. CLINICAL RELEVANCE STATEMENT: Spectral CT has added value for spread through air spaces prediction in lung adenocarcinoma so may impact treatment planning in the future. KEY POINTS: • Electronic density may be a potential spectral index for predicting spread through air spaces in lung adenocarcinoma. • A combination of spectral and traditional CT features enhances the performance of traditional CT for predicting spread through air spaces.

Photochemical α-selective radical ring-opening reactions of 1,3-disubstituted acyl bicyclobutanes with alkyl halides: modular access to functionalized cyclobutenes.

Although ring-opening reactions of bicyclobutanes bearing electron-withdrawing groups, typically with ß-selectivity, have evolved as a powerful platform for synthesis of cyclobutanes, their application in the synthesis of cyclobutenes remains underdeveloped. Here, a novel visible light induced α-selective radical ring-opening reaction of 1,3-disubstituted acyl bicyclobutanes with alkyl radical precursors for the synthesis of functionalized cyclobutenes is described. In particular, primary, secondary, and tertiary alkyl halides are all suitable substrates for this photocatalytic transformation, providing ready access to cyclobutenes with a single all-carbon quaternary center, or with two contiguous centers under mild reaction conditions.

C(sp2)-H cyclobutylation of hydroxyarenes enabled by silver-π-acid catalysis: diastereocontrolled synthesis of 1,3-difunctionalized cyclobutanes.

Ring-opening of bicyclo[1.1.0]butanes (BCBs) is emerging as a powerful strategy for 1,3-difunctionalized cyclobutane synthesis. However, reported radical strain-release reactions are typically plagued with diastereoselectivity issues. Herein, an atom-economic protocol for the highly chemo- and diastereoselective polar strain-release ring-opening of BCBs with hydroxyarenes catalyzed by a π-acid catalyst AgBF4 has been developed. The use of readily available starting materials, low catalyst loading, high selectivity (up to >98 : 2 d.r.), a broad substrate scope, ease of scale-up, and versatile functionalizations of the cyclobutane products make this approach very attractive for the synthesis of 1,1,3-trisubstituted cyclobutanes. Moreover, control experiments and theoretical calculations were performed to illustrate the reaction mechanism and selectivity.