Observation of the Transition from Triple Bonds to Single Bonds between Ru-Ge Bonding in RuGeO(CO)n- (n = 3-5).

This work reports the observation and characterization of heterobinuclear transition-metal main-group metal oxide carbonyl complex anions, RuGeO(CO)n- (n = 3-5), by combining mass-selected photoelectron velocity map imaging spectroscopy and quantum chemistry calculations. The experimentally determined vertical electron detachment energy of RuGeO(CO)3- surpasses those of RuGeO(CO)4- and RuGeO(CO)5-, which is attributed to distinctive bonding features. RuGeO(CO)3- manifests one covalent σ and two Ru-to-Ge dative π bonds, contrasting with the sole covalent σ bond present in RuGeO(CO)4- and RuGeO(CO)5-. Unpaired spin density distribution analysis reveals a 17-electron configuration at the Ru center in RuGeO(CO)3- and an 18-electron configuration in RuGeO(CO)4- and RuGeO(CO)5-. This work closes a gap in the quantitative physicochemical characterization of heteronuclear oxide carbonyl complexes, enhancing our insights into catalytic processes of CO/GeO on the metal surface at the molecular level.

Rice floury endosperm26 encoding a mitochondrial single-stranded DNA-binding protein is essential for RNA-splicing of mitochondrial genes and endosperm development.

Endosperm, the major storage organ in cereal grains, determines the grain yield and quality. Mitochondria provide the energy for dry matter accumulation, in the endosperm development. Although mitochondrial single-stranded DNA-binding proteins (mtSSBs) play a canonical role in the maintenance of single-stranded mitochondrial DNA, their molecular functions in RNA processing and endosperm development remain obscure. Here, we report a defective rice endosperm mutant, floury endosperm26 (flo26), which develops abnormal starch grains in the endosperm. Map-based cloning and complementation experiments showed that FLO26 allele encodes a mitochondrial single-stranded DNA-binding protein, named as mtSSB1.1. Loss of function of mtSSB1.1 affects the transcriptional level of many mitochondrially-encoded genes and RNA splicing of nad1, a core component of respiratory chain complex I in mitochondria. As a result, dysfunctional mature nad1 led to dramatically decreased complex I activity, thereby reducing ATP production. Our results reveal that mtSSB1.1 plays an important role in the maintenance of mitochondrial function and endosperm development by stabilizing the splicing of mitochondrial RNA in rice.

Reflectance confocal microscopy for the early diagnosis of herpes zoster.

For herpes zoster (HZ) infection, early diagnosis and treatment are important in order to shorten the course of the disease and reduce sequelae, however, there is a lack of non-invasive diagnostic methods. Reflectance confocal microscopy (RCM) is a non-invasive technique often used to diagnose dyspigmented dermatosis, skin tumours, human papillomavirus infectious dermatosis, etc. To evaluate the clinical value of RCM for the early diagnosis of HZ. We collected RCM images from 30 HZ patients with typical vesicles in order to analyse their features. We then utilized RCM to analyse early lesions of another 12 HZ patients, who presented with localized erythema or papules, but not typical vesicles. In addition, we recruited one patient with HZ and observed the lesions over 14 days also using RCM. RCM images showed that the typical lesions of HZ mainly involved oedema of the spinous layer, intraepidermal blister formation, ballooning multinucleated giant (BMG) cells, and dermal papillary oedema. Among them, BMG cells were of specific diagnostic value. Early lesions of HZ patients without typical vesicles showed BMG cells under RCM. A few BMG cells were observed during the early stage of HZ. However, the number of BMG cells increased significantly as typical clustered blisters gradually appeared in the lesions. With the regression of the lesions, the number of BMG cells decreased gradually. RCM, with the advantages of being non-invasive, rapid, and convenient, has an important role in monitoring the evolution of HZ.

GFPBW1, a ß-glucan from Grifola frondosa as vaccine adjuvant: APCs activation and maturation.

Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous ß-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 µg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 µg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.

Green synthesis of a superhydrophobic porous organic polymer for the removal of volatile organic compounds at high humidity.

Superhydrophobic porous organic polymers are potential sorbents for volatile organic compounds (VOCs) pollution control by suppressing the competition of water molecules on their surfaces. However, the synthesis of superhydrophobic reagents usually requires large amounts of organic solvents and a long reaction time (≥ 24 h). Herein, a green mechanochemical method was developed to synthesize a superhydrophobic polymer (MSHMP-1) with the advantages of using a small amount of organic solvents (5 mL/g) and a short reaction time (2 h). Meanwhile, MSHMP-1 with a water contact angle (WCA) of 162° exhibited a dramatically rich pore structure as revealed by its specific surface area (SSA) of 1780 m2/g. The decrease in the adsorption of benzene on MSHMP-1 due to the competition of water molecules, even at relative humidity of 90 %, was nonsignificant (<10 %), indicating the great application potential of MSHMP-1 in hydrophobic adsorption. Moreover, the adsorption capacity of MSHMP-1 was maintained after at least five adsorption-desorption cycles. Therefore, MSHMP-1 can be a remarkable adsorbent for the removal of hazardous VOCs, especially at high humidity levels.

Single-cell RNA sequencing reveals the MIF/ACKR3 receptor-ligand interaction between neutrophils and nucleus pulposus cells in intervertebral disc degeneration.

OBJECTIVES: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD). METHODS: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo. RESULTS: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF+ ECMO-neutrophil counts and ACKR3+ effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors. CONCLUSIONS: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies.

E3 ligase DECREASED GRAIN SIZE 1 promotes degradation of a G-protein subunit and positively regulates grain size in rice.

Grain size is one of the most important traits determining crop yield. However, the mechanism controlling grain size remains unclear. Here, we confirmed the E3 ligase activity of DECREASED GRAIN SIZE 1 (DGS1) in positive regulation of grain size in rice (Oryza sativa) suggested in a previous study. Rice G-protein subunit gamma 2 (RGG2), which negatively regulates grain size, was identified as an interacting protein of DGS1. Biochemical analysis suggested that DGS1 specifically interacts with canonical Gγ subunits (rice G-protein subunit gamma 1 [RGG1] and rice G-protein subunit gamma 2 [RGG2]) rather than non-canonical Gγ subunits (DENSE AND ERECT PANICLE 1 [DEP1], rice G-protein gamma subunit type C 2 [GCC2], GRAIN SIZE 3 [GS3]). We also identified the necessary domains for interaction between DGS1 and RGG2. As an E3 ligase, DGS1 ubiquitinated and degraded RGG2 via a proteasome pathway in several experiments. DGS1 also ubiquitinated RGG2 by its K140, K145 and S147 residues. Thus, this work identified a substrate of the E3 ligase DGS1 and elucidated the post transcriptional regulatory mechanism of the G-protein signalling pathway in the control of grain size.

Enantioselective copper-catalyzed azidation/click cascade reaction for access to chiral 1,2,3-triazoles.

Chiral 1,2,3-triazoles are highly attractive motifs in various fields. However, achieving catalytic asymmetric click reactions of azides and alkynes for chiral triazole synthesis remains a significant challenge, mainly due to the limited catalytic systems and substrate scope. Herein, we report an enantioselective azidation/click cascade reaction of N-propargyl-ß-ketoamides with a readily available and potent azido transfer reagent via copper catalysis, which affords a variety of chiral 1,2,3-triazoles with up to 99% yield and 95% ee under mild conditions. Notably, chiral 1,5-disubstituted triazoles that have not been accessed by previous asymmetric click reactions are also prepared with good functional group tolerance.

Multifunctional Fe/Cu Dual-Single Atom Nanozymes with Enhanced Peroxidase Activity for Isoniazid Detection and Levofloxacin Degradation.

The design of single-atom nanozymes with dual active sites to increase their activity and for the detection and degradation of contaminants is rare and challenging. In this work, a single-atom nanozyme (FeCu-NC) based on a three-dimensional porous Fe/Cu dual active site was developed as a colorimetric sensor for both the quantitative analysis of isoniazid (INH) and the efficient degradation of levofloxacin (LEV). FeCu-NC was synthesized using a salt template and freeze-drying method with a three-dimensional hollow porous structure and dual active sites (Fe-Nx and Cu-Nx). In terms of morphology and structure, FeCu-NC exhibits excellent peroxidase-like activity and catalytic properties. Therefore, a colorimetric sensor was constructed around FeCu-NC for sensitive and rapid quantitative analysis of INH with a linear range of 0.9-10 µM and a detection limit as low as 0.3 µM, and the sensor was successfully applied to the analysis of INH in human urine. In addition, FeCu-NC promoted the efficient degradation of LEV by peroxymonosulfate activation, with a degradation rate of 90.4% for LEV at 30 min. This work sheds new light on the application of single-atom nanozymes to antibiotics for colorimetric sensing and degradation.

The RNA binding protein EHD6 recruits the m6A reader YTH07 and sequesters OsCOL4 mRNA into phase-separated ribonucleoprotein condensates to promote rice flowering.

N6-Methyladenosine (m6A) is one of the most abundant modifications of eukaryotic mRNA, but its comprehensive biological functionality remains further exploration. In this study, we identified and characterized a new flowering-promoting gene, EARLY HEADING DATE6 (EHD6), in rice. EHD6 encodes an RNA recognition motif (RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein (RNP) granules and can bind both m6A-modified RNA and unmodified RNA indiscriminately. We found that EHD6 can physically interact with YTH07, a YTH (YT521-B homology) domain-containing m6A reader. We showed that their interaction enhances the binding of an m6A-modified RNA and triggers relocation of a portion of YTH07 from the cytoplasm into RNP granules through phase-separated condensation. Within these condensates, the mRNA of a rice flowering repressor, CONSTANS-like 4 (OsCOL4), becomes sequestered, leading to a reduction in its protein abundance and thus accelerated flowering through the Early heading date 1 pathway. Taken together, these results not only shed new light on the molecular mechanism of efficient m6A recognition by the collaboration between an RNA binding protein and YTH family m6A reader, but also uncover the potential for m6A-mediated translation regulation through phase-separated ribonucleoprotein condensation in rice.

OsSRF8 interacts with OsINP1 and OsDAF1 to regulate pollen aperture formation in rice.

In higher plants, mature male gametophytes have distinct apertures. After pollination, pollen grains germinate, and a pollen tube grows from the aperture to deliver sperm cells to the embryo sac, completing fertilization. In rice, the pollen aperture has a single-pore structure with a collar-like annulus and a plug-like operculum. A crucial step in aperture development is the formation of aperture plasma membrane protrusion (APMP) at the distal polar region of the microspore during the late tetrad stage. Previous studies identified OsINP1 and OsDAF1 as essential regulators of APMP and pollen aperture formation in rice, but their precise molecular mechanisms remain unclear. We demonstrate that the Poaceae-specific OsSRF8 gene, encoding a STRUBBELIG-receptor family 8 protein, is essential for pollen aperture formation in Oryza sativa. Mutants lacking functional OsSRF8 exhibit defects in APMP and pollen aperture formation, like loss-of-function OsINP1 mutants. OsSRF8 is specifically expressed during early anther development and initially diffusely distributed in the microsporocytes. At the tetrad stage, OsSRF8 is recruited by OsINP1 to the pre-aperture region through direct protein-protein interaction, promoting APMP formation. The OsSRF8-OsINP1 complex then recruits OsDAF1 to the APMP site to co-regulate annulus formation. Our findings provide insights into the mechanisms controlling pollen aperture formation in cereal species.

Direct Observation of Covalently Bound Clusters in Resonantly Stabilized Radical Reactions and Implications for Carbonaceous Particle Growth.

Based on quantum mechanically guided experiments that observed elusive intermediates in the domain of inception that lies between large molecules and soot particles, we provide a new mechanism for the formation of carbonaceous particles from gas-phase molecular precursors. We investigated the clustering behavior of resonantly stabilized radicals (RSRs) and their interactions with unsaturated hydrocarbons through a combination of gas-phase reaction experiments and theoretical calculations. Our research directly observed a sequence of covalently bound clusters (CBCs) as key intermediates in the evolution from small RSRs, such as benzyl (C7H7), indenyl (C9H7), 1-methylnaphthyl (1-C11H9), and 2-methylnaphthyl (2-C11H9), to large polycyclic aromatic hydrocarbons (PAHs) consisting of 28 to 55 carbons. We found that hydrogen abstraction and RSR addition drive the formation and growth of CBCs, leading to progressive H-losses, the generation of large PAHs and PAH radicals, and the formation of white smoke (incipient carbonaceous particles). This mechanism of progressive H-losses from CBCs (PHLCBC) elucidates the crucial relationship among RSRs, CBCs, and PAHs, and this study provides an unprecedentedly seamless path of observed assembly from small RSRs to large nanoparticles. Understanding the PHLCBC mechanism over a wide temperature range may enhance the accuracy of multiscale models of soot formation, guide the synthesis of carbonaceous nanomaterials, and deepen our understanding of the origin and evolution of carbon within our galaxy.

Olfactory dysfunction and the role of stem cells in the regeneration of olfactory neurons.

The prevalence of COVID-19 has drawn increasing attention to olfactory dysfunction among researchers. Olfactory dysfunction manifests in various clinical types, influenced by numerous pathogenic factors. Despite this diversity, the underlying pathogenesis remains largely elusive, contributing to a lack of standardized treatment approaches. However, the potential regeneration of olfactory neurons within the nasal cavity presents a promising avenue for addressing olfactory dysfunction effectively. Our review aims to delve into the current research landscape and treatment modalities concerning olfactory dysfunction, emphasizing etiology, pathogenesis, clinical interventions, and the role of stem cells in regenerating olfactory nerves. Through this comprehensive examination, we aim to provide valuable insights into understanding the onset, progression, and treatment of olfactory dysfunction diseases.

Age-related trajectories of the development of social cognition.

Age-related trajectories of intrinsic functional connectivity (iFC), which represent the interconnections between discrete regions of the human brain, for processes related to social cognition (SC) provide evidence for social development through neural imaging and can guide clinical interventions when such development is atypical. However, due to the lack of studies investigating brain development over a wide range of ages, the neural mechanisms of SC remain poorly understood, although considerable behavior-related evidence is available. The present study mapped vortex-wise iFC features between SC networks and the entire cerebral cortex by using common functional networks, creating the corresponding age-related trajectories. Three networks [moral cognition, theory of mind (ToM), and empathy] were selected as representative SC networks. The Enhanced Nathan Kline Institute-Rockland Sample (NKI-RS, N = 316, ages 8-83 years old) was employed delineate iFC characteristics and construct trajectories. The results showed that the SC networks display unique and overlapping iFC profiles. The iFC of the empathy network, an age-sensitive network, with dorsal attention network was found to exhibit a linear increasing pattern, that of the ventral attention network was observed to exhibit a linear decreasing pattern, and that of the somatomotor and dorsal attention networks was noted to exhibit a quadric-concave iFC pattern. Additionally, a sex-specific effect was observed for the empathy network as it exhibits linear and quadric sex-based differences in iFC with the frontoparietal and vision networks, respectively. The iFC of the ToM network with the ventral attention network exhibits a pronounced quadric-convex (inverted U-shape) trajectory. No linear or quadratic trajectories were noted in the iFC of the moral cognition network. These findings indicate that SC networks exhibit iFC with both low-level (somatomotor, vision) and high-level (attention and control) networks along specific developmental trajectories. The age-related trajectories determined in this study advance our understanding of the neural mechanisms of SC, providing valuable references for identification and intervention in cases of development of atypical SC.

Appraisal of clinical practice guidelines and consensus statements on obstetric anaesthesia: a systematic review using the AGREE II instrument.

OBJECTIVES: Despite the publication of hundreds of trials on obstetric anaesthesia, the management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for obstetric anaesthesia. DESIGN: This is a systematic review and quality assessment using the Appraisal of Guidelines for Research and Evaluation (AGREE) II methodology. DATA SOURCES: Data sources include PubMed and Embase (8 June 2023), three Chinese academic databases, six guideline databases (7 June 2023) and Google and Google scholar (1 August 2023). ELIGIBILITY CRITERIA: We included the latest version of international and national/regional clinical practice guidelines and consensus statements for the anaesthetic management of pregnant patients during labour, non-operative delivery, operative delivery and selected aspects of perioperative monitoring, postpartum care and analgesia, published in English or Chinese. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the searched items and extracted data. Four reviewers independently scored documents using AGREE II. Recommendations from all documents were tabulated and visualised in a coloured grid. RESULTS: Twenty-two guidance documents (14 clinical practice guidelines and 8 consensus statements) were included. Included documents performed well in the domains of scope and purpose (median 76.4%, IQR 69.4%-79.2%) and clarity of presentation (median 72.2%, IQR 61.1%-80.6%), but were unsatisfactory in applicability (median 21.9%, IQR 13.5%-27.1%) and editorial independence (median 47.9%, IQR 6.3%-73.2%). The majority of obstetric anaesthesia guidelines or consensus centred on different topics. Less than 30% of them specifically addressed the management of obstetric anaesthesia perioperatively. Recommendations were concordant on the perioperative preparation, and on some indications for the choice of anaesthesia method. Substantially different recommendations were provided for some items, especially for preoperative blood type and screen, and for the types and doses of neuraxial administration. CONCLUSIONS: The methodological quality in guidance documents for obstetric anaesthesia necessitates enhancement. Despite numerous trials in this area, evidence gaps persist for specific clinical queries in this field. One potential approach to mitigate these challenges involves the endorsement of standardised guidance development methods and the synthesis of robust clinical evidence, aimed at diminishing difference in recommendations.

Development and characterization of a bacterial enzyme cascade reaction system for efficient and stable PET degradation.

The widespread use of polyethylene terephthalate (PET) in various industries has led to a surge in microplastics (MPs) pollution, posing a significant threat to ecosystems and human health. To address this, we have developed a bacterial enzyme cascade reaction system (BECRS) that focuses on the efficient degradation of PET. This system harnesses the Escherichia coli (E. coli) surface to display CsgA protein, which forms curli fibers, along with the carbohydrate-binding module 3 (CBM3) and PETases, to enhance the adsorption and degradation of PET. The study demonstrated that the BECRS achieved a notable PET film degradation rate of 3437 ± 148 µg/(d*cm²), with a degradation efficiency of 21.40% for crystalline PET MPs, and the degradation products were all converted to TPA. The stability of the system was evidenced by retaining over 80% of its original activity after multiple uses and during one month of storage. Molecular dynamics simulations confirmed that the presence of CsgA did not interfere with the enzymatic activity of PETases. This BECRS represents a significant step forward in the biodegradation of PET, particularly microplastics, offering a practical and sustainable solution for environmental pollution control.

Coupling protein scaffold and biosilicification: A sustainable and recyclable approach for d-mannitol production via one-step purification and immobilization of multienzymes.

Enzymatic synthesis of biochemicals in vitro is vital in synthetic biology for its efficiency, minimal by-products, and easy product separation. However, challenges like enzyme preparation, stability, and reusability persist. Here, we introduced a protein scaffold and biosilicification coupled system, providing a singular process for the purification and immobilization of multiple enzymes. Using d-mannitol as a model, we initially constructed a self-assembling EE/KK protein scaffold for the co-immobilization of glucose dehydrogenase and mannitol dehydrogenase. Under an enzyme-to-scaffold ratio of 1:8, a d-mannitol yield of 0.692 mol/mol was achieved within 4 h, 2.16-fold higher than the free enzymes. The immobilized enzymes retained 70.9 % of the initial joint activity while the free ones diminished nearly to inactivity after 8 h. Furthermore, we incorporated the biosilicification peptide CotB into the EE/KK scaffold, inducing silica deposition, which enabled the one-step purification and immobilization process assisted by Spy/Snoop protein-peptide pairs. The coupled system demonstrated a comparable d-mannitol yield to that of EE/KK scaffold and 1.34-fold higher remaining activities after 36 h. Following 6 cycles of reaction, the immobilized system retained the capability to synthesize 56.4 % of the initial d-mannitol titer. The self-assembly co-immobilization platform offers an effective approach for enzymatic synthesis of d-mannitol and other biochemicals.

Anti-MRSA mechanism of spirostane saponin in Rohdea pachynema F.T.Wang & tang.

ETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components. AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism. MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo. RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 µg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg). CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.

RSU-1 regulates the integrity of dense bodies in muscle cells of aging Caenorhabditis elegans.

Muscle contraction is vital for animal survival, and the sarcomere is the fundamental unit for this process. However, the functions of many conserved sarcomere proteins remain unknown, as their mutants do not exhibit obvious defects. To address this, Caenorhabditis elegans was utilized as a model organism to investigate RSU-1 function in the body wall muscle. RSU-1 is found to colocalize with UNC-97 at the dense body and M-line, and it is particularly crucial for regulating locomotion in aging worms, rather than in young worms. This suggests that RSU-1 has a specific function in maintaining muscle function during aging. Furthermore, the interaction between RSU-1 and UNC-97/PINCH is essential for RSU-1 to modulate locomotion, preserve filament structure, and sustain the M-line and dense body throughout aging. Overall, these findings highlight the significant contribution of RSU-1, through its interaction with UNC-97, in maintaining proper muscle cell function in aging worms.

LncRNA-NEAT1 blocks the Wnt/ß-catenin signaling pathway by targeting miR-217 to inhibit trophoblast cell migration and invasion.

OBJECTIVE: This study aimed to study the correlation between preeclampsia (PE) and lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and to examine the molecular mechanisms behind the development of PE. METHODS: 30 PE and 30 normal pregnant women placental samples were assessed the levels of NEAT1 and miR-217 by quantitative real-time PCR (qRT-PCR). The trophoblast cell line HTR8/SVneo was used for silencing NEAT1 or miR-217 inhibitor in the absence or presence of an inhibitor and H2O2. Cell counting Kit 8 (CCK-8), flow cytometry, and Transwell were used to detect cell proliferation, apoptosis, migration, and invasion. Luciferase reporter gene assay was utilized to verify the binding between miR-217 and Wnt family member 3 (Wnt3), and between the miR-217 and NEAT1. Proteins related to the Wnt/ß-catenin signaling pathway were detected using western blotting. RESULTS: The PE group exhibited a significantly downregulated expression of miR-217 and a significantly upregulated expression of NEAT1. NEAT1 targeted miR-217, and Wnt is a miR-217 target gene. siRNA-NEAT1 inhibited the apoptosis of trophoblast cells, but promoted their invasion, migration, and proliferation. MiR-217 inhibitor could partially reverse the effects of siRNA-NEAT1. The expression of the Wnt/ß-catenin signaling pathway-related proteins, WNT signaling pathway inhibitor 1 (DKK1), cyclin-D1 and ß-catenin, was significantly increased after siRNA-NEAT1. CONCLUSIONS: NEAT1 could reduce trophoblast cell invasion and migration by suppressing miR-217/Wnt signaling pathway, leading to PE.