Changes in slow-wave sleep characteristics in Parkinson's disease patients with mild-moderate depression.

INTRODUCTION: Depression and sleep disturbances are commonly seen non-motor symptoms in patients with Parkinson's disease (PD). This study used polysomnography to examine the relationship between mild-moderate depression in PD and sleep characteristics, particularly slow wave activities (SWA). METHODS: 59 PD patients were split into two groups: nd-PD (n = 27) (patients with PD without depression) and d-PD (n = 32) (patients with PD with mild-moderate depression). Their clinical features, polysomnography parameters, and demographics were evaluated. Early and late sleep SWA spectrum densities and overnight SWA decline in different brain regions were particularly analyzed. RESULTS: Non-rapid eye movement 3 (N3) sleep duration and percentage were greater in the d-PD group. N3 percentage was linked to depression (p = 0.014). During late sleep, higher SWA (0.5-4Hz) in the frontal and central regions, higher low-SWA (0.5-2Hz) in the whole brain, central and occipital regions, and higher high-SWA (2-4Hz) in the frontal region was observed in the d-PD group. During early sleep, there was also higher low-SWA (0.5-2Hz) in the occipital region. Patients in d-PD group exhibited reduced overnight high-SWA (2-4Hz) decline (Δhigh-SWA) in the whole brain and occipital regions. Δhigh-SWA(2-4Hz) in the occipital region were associated with depression (p = 0.049). CONCLUSION: PD patients with mild-moderate depression have impaired slow wave sleep, exhibiting as increased N3 sleep, SWA, and reduced overnight SWA decline. This implies that synaptic strength reduction during sleep and impaired synaptic homeostasis regulation may be associated with depression in PD. Reduced overnight high-SWA decline in the occipital region may serve as a novel electrophysiological biomarker for indicating depression in PD.

Salvianolic acid B inhibits thrombosis and directly blocks the thrombin catalytic site.

Background: Salvianolic acid B (SAB) is a major component of Salvia miltiorrhiza root (Danshen), widely used in East/Southeast Asia for centuries to treat cardiovascular diseases. Danshen depside salt, 85% of which is made up of SAB, is approved in China to treat chronic angina. Although clinical observations suggest that Danshen extracts inhibited arterial and venous thrombosis, the exact mechanism has not been adequately elucidated. Objective: To delineate the antithrombotic mechanisms of SAB. Methods: We applied platelet aggregation and coagulation assays, perfusion chambers, and intravital microscopy models. The inhibition kinetics and binding affinity of SAB to thrombin are measured by thrombin enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. We used molecular in silico docking models to predict the interactions of SAB with thrombin. Results: SAB dose-dependently inhibited platelet activation and aggregation induced by thrombin. SAB also reduced platelet aggregation induced by adenosine diphosphate and collagen. SAB attenuated blood coagulation by modifying fibrin network structures and significantly decreased thrombus formation in mouse cremaster arterioles and perfusion chambers. The direct SAB-thrombin interaction was confirmed by enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. Interestingly, SAB shares key structural similarities with the trisubstituted benzimidazole class of thrombin inhibitors, such as dabigatran. Molecular docking models predicted the binding of SAB to the thrombin active site. Conclusion: Our data established SAB as the first herb-derived direct thrombin catalytic site inhibitor, suppressing thrombosis through both thrombin-dependent and thrombin-independent pathways. Purified SAB may be a cost-effective agent for treating arterial and deep vein thrombosis.

Efficacy and safety of Lianhua Qingwen granule combined with azithromycin for mycoplasma pneumoniae pneumonia in children: a systematic review with meta-analysis and trial sequential analysis.

Background: Lianhua Qingwen (LHQW) granule, a botanical drug preparation, is frequently utilized as an adjuvant treatment for mycoplasma pneumoniae pneumonia (MPP). Nevertheless, the clinical efficacy and safety of this treatment remain uncertain. Purpose: This study aims to evaluate the efficacy and safety of LHQW granule combined with azithromycin (AZM) in treating MPP in children. Method: To identify all randomized controlled trials (RCTs) of LHQW granule plus AZM, a search was conducted in eight Chinese and English databases (CNKI, Wan Fang, VIP, Sinomed, PubMed, Embase, Web of Science, and Cochrane Library) from their inception until 25 December 2023. Meta-regression and subgroup analysis were employed to investigate heterogeneity. Sensitivity analysis and trial sequential analysis (TSA) were conducted to assess the robustness of the findings. Additionally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was utilized to evaluate the quality of evidence. Results: A total of 15 RCTs involving 1909 participants were included in this study. The meta-analysis results indicated combination therapy of LHQW granule and AZM is significant different from AZM alone in both efficacy and safety, which are specifically observed in the following outcomes: response rate (RR = 1.17, 95% CI: 1.12 to 1.22, p < 0.01), antipyretic time (MD = -1.32, 95% CI: -1.66 to -0.98, p < 0.01), cough disappearance time (MD = -1.76, 95% CI: -2.47 to -1.05, p < 0.01), pulmonary rale disappearance time (MD = -1.54, 95% CI: -2.06 to -1.02, p < 0.01), c-reactive protein (CRP) (MD = -5.50, 95% CI: -6.92 to -4.07, p < 0.01), procalcitonin (PCT) (MD = -0.31, 95% CI: -0.38 to -0.24, p < 0.01), interleukin 6 (IL-6) (MD = -5.97, 95% CI: -7.39 to -4.54, p<0.01), tumor necrosis factor α (TNF-α) (MD = -5.74, 95% CI: -7.44 to -4.04, p < 0.01), forced vital capacity (FVC) (SMD = 0.48, 95% CI: 0.34 to 0.62, p < 0.01), forced expiratory volume in the first second (FEV1) (SMD = 0.55, 95% CI: 0.44 to 0.67, p < 0.01), FEV1/FVC (SMD = 0.49, 95% CI: 0.32 to 0.67, p < 0.01), CD4+ T lymphocyte (CD4+) (MD = 4.04, 95% CI: 3.09 to 4.98, p < 0.01), CD8+ T lymphocyte (CD8+) (MD = -3.32, 95% CI: 4.27 to 2.38, p < 0.01) and adverse events (RR = 0.65, 95% CI: 0.43 to 0.96, p < 0.01). Conclusion: The combination therapy of LHQW granule and AZM may be a better strategy to treat MPP in children. However, the clinical efficacy and safety of LHQW granule require further validation. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/.

Experimental study on the mechanical characteristics of weakly cemented mudstone under different loading rates.

With the gradual shift of coal mining to the western coal mining region of China, floor heave in weakly cemented mudstone roadways has become an issue affecting the safety and efficiency of coal mine production. Additionally, different mining rates can lead to fluctuating support stresses on the roof and floor of weakly cemented mudstone roadways. Therefore, obtaining a comprehensive understanding of the mechanical properties of weakly cemented mudstone at different loading rates is conducive to improving the issue of floor heave in such roadways and provides a theoretical basis for further study. In this context, a series of uniaxial mechanical tests with concurrent acoustic emission monitoring were conducted on specimens of weakly cemented mudstone under various loading rates (0.005, 0.01, 0.05, and 0.1 mm/s). The stress‒strain and acoustic emission response curves were obtained to effectively characterize the strength, deformation, damage, macroscale instability, and crack propagation characteristics of the mudstone under the influence of loading rate effects. The research results support the following findings: (1) With increasing loading rate, the peak strength and elastic modulus of weakly cemented mudstone significantly increase, while the peak axial strain and peak radial deformation significantly decrease. (2) With increasing loading rate, the stress required to trigger the expansion of weakly cemented mudstone gradually increases, and a significant power-law relationship arises between the strain of the mudstone at the start of expansion and the loading rate. (3) With increasing loading rate, the acoustic emission ringing count of weakly cemented mudstone increases: The failure of weakly cemented mudstone changes from small-range progressive failure to sudden failure, and the failure mode transitions from shear failure to tensile‒shear composite failure. (4) The studied mudstone damage variables increase with increasing loading rate, following an approximate exponential function. The conclusions obtained in this work can provide a theoretical basis for the evolution mechanism and control of floor heave in deep roadway mining.

Light-Triggered Anti-ambipolar Transistor Based on an In-Plane Lateral Homojunction.

Currently, the construction of anti-ambipolar transistors (AATs) is primarily based on asymmetric heterostructures, which are challenging to fabricate. AATs used for photodetection are accompanied by dark currents that prove difficult to suppress, resulting in reduced sensitivity. This work presents light-triggered AATs based on an in-plane lateral WSe2 homojunction without van der Waals heterostructures. In this device, the WSe2 channel is partially electrically controlled by the back gate due to the screening effect of the bottom electrode, resulting in a homojunction that is dynamically modulated with gate voltage, exhibiting electrostatically reconfigurable and light-triggered anti-ambipolar behaviors. It exhibits high responsivity (188 A/W) and detectivity (8.94 × 1014 Jones) under 635 nm illumination with a low power density of 0.23 µW/cm2, promising a new approach to low-power, high-performance photodetectors. Moreover, the device demonstrates efficient self-driven photodetection. Furthermore, ternary inverters are realized using monolithic WSe2, simplifying the manufacturing of multivalued logic devices.

A dataset of riverine nitrogen yield across watersheds in the Conterminous United States.

Riverine nitrogen is a pivotal determinant influencing water quality in inland and coastal waters. Despite the recognized utility, no spatially-explicit data on riverine nitrogen yield is available for large parts of the world, thus hindering our ability to identify the contributors to riverine nitrogen and understand aquatic nitrogen cycling. To fill the data gap for the United States, here we (1) compiled 294,996 total nitrogen (TN), 225,827 nitrate (NO3-), 204,015 ammonium (NH4+), and 158,837 total organic nitrogen (TON) concentrations, with concurrent streamflow data, across the Conterminous United States (CONUS), (2) estimated riverine nitrogen loads for over 1,800 hydrological stations, (3) derived the spatial distribution of annual riverine nitrogen yield by leveraging river and catchment connectivity information contained in the National Hydrography Dataset plus (NHDPlus), and (4) characterized nonpoint-source TN loads by excluding point-source loads. This new spatial dataset quantifies spatial sources of nitrogen yield from point and non-point sources (e.g., up to 36% from point sources across the U.S.) and serves as ground-truthing to validate water quality models.

Association between dietary quality and accelerated aging: a cross-sectional study of two cohorts.

Background: Diet quality significantly influences aging processes and age-related health outcomes. This study aims to explore the association between dietary quality and accelerated aging in two large cohorts. Methods: This study collected data from the Kailuan and National Health and Nutrition Examination Survey (NHANES) cohorts; participants' dietary quality was evaluated using the American Heart Association (AHA) dietary score and Healthy Eating Index-2015 (HEI-2015), respectively. Accelerated aging in participants was determined by calculating the difference between phenotypic age and chronological age. Logistic regression models were used to explore the association between dietary quality scores and accelerated aging. Additionally, variations in this association across different subgroups were investigated. To minimize the influence of excessive aging, individuals aged 75 and above were excluded in sensitivity analyses. Results: In this study, we included 33 701 participants (27.3% female, mean age 57.29 ± 11.88) from the Kailuan study and 9285 participants (50.6% female, mean age 49.83 ± 17.62) from NHANES. In the Kailuan cohort, individuals with dietary scores ranging from 3 to 5 exhibited a 22% lower risk of accelerated aging compared to those scoring between 0 and 2 (OR = 0.78, 95% CI = 0.72-0.85). Similarly, in the NHANES cohort, participants in the highest quartile of HEI-2015 experienced a 34% reduction in the risk of accelerated aging compared to those in the lowest quartile (OR = 0.66, 95% CI = 0.52-0.84). Subgroup analyses underscored a more pronounced association between dietary quality and accelerated aging among males and individuals with unhealthy lifestyles. Sensitivity analyses confirmed the robustness of the association between dietary quality and accelerated aging. Conclusion: In summary, our study found a significant association between dietary quality and accelerated aging. Better dietary quality was associated with a reduced risk of accelerated aging, particularly among males, smokers, and participants with unhealthy lifestyles.

miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization.

BACKGROUND: Colorectal cancer is among the most common malignant tumors affecting the gastrointestinal tract. Liver metastases, a complication present in approximately 50% of colorectal cancer patients, are a considerable concern. Recently, studies have revealed the crucial role of miR-455 in tumor pathogenesis. However, the effect of miR-455 on the progression of liver metastases in colorectal cancer remains controversial. As an antagonist of bone morphogenetic protein(BMP), Gremlin 1 (GREM1) may impact organogenesis, body patterning, and tissue differentiation. Nevertheless, the role of miR-455 in regulating GREM1 in colorectal cancer liver metastases and how miR-455/GREM1 axis influences tumour immune microenvironment is unclear. METHODS: Bioinformatics analysis shows that miR-455/GREM1 axis plays crucial role in liver metastasis of intestinal cancer and predicts its possible mechanism. To investigate the impact of miR-455/GREM1 axis on the proliferation, invasion, and migration of colorectal cancer cells, colony formation assay, wound healing and transwell assay were examined in vitro. The Dual-Luciferase reporter gene assay and RNA pull-down assay confirmed a possible regulatory effect between miR-455 and GREM1. In vivo, colorectal cancer liver metastasis(CRLM) model mice was established to inquiry the effect of miR-455/GREM1 axis on tumor growth and macrophage polarization. The marker of macrophage polarization was tested using immunofluorescence(IF) and quantitative real-time polymerase chain reaction(qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), cytokines were detected in culture medium supernatants. RESULTS: We found that miR-455 and BMP6 expression was increased and GREM1 expression was decreased in liver metastase compared with primary tumor. miR-455/GREM1 axis promotes colorectal cancer cells proliferation, migration, invasion via affected PI3K/AKT pathway. Moreover, downregulating GREM1 augmented BMP6 expression in MC38 cell lines, inducing M2 polarization of macrophages, and promoting liver metastasis growth in CRLM model mice. CONCLUSION: These data suggest that miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization. These results offer valuable insights and direction for future research and treatment of CRLM.

Multi-omics analysis of Streptomyces djakartensis strain MEPS155 reveal a molecular response strategy combating Ceratocystis fimbriata causing sweet potato black rot.

To investigate the potential antifungal mechanisms of rhizosphere Actinobacteria against Ceratocystis fimbriata in sweet potato, a comprehensive approach combining biochemical analyses and multi-omics techniques was employed in this study. A total of 163 bacterial strains were isolated from the rhizosphere soil of sweet potato. Among them, strain MEPS155, identified as Streptomyces djakartensis, exhibited robust and consistent inhibition of C. fimbriata mycelial growth in in vitro dual culture assays, attributed to both cell-free supernatant and volatile organic compounds. Moreover, strain MEPS155 demonstrated diverse plant growth-promoting attributes, including the production of indole-3-acetic acid, 1-aminocyclopropane-1-carboxylate deaminase, phosphorus solubilization, nitrogen fixation, and enzymatic activities such as cellulase, chitinase, and protease. Notably, strain MEPS155 exhibited efficacy against various sweet potato pathogenic fungi. Following the inoculation of strain MEPS155, a significant reduction (P < 0.05) in malondialdehyde content was observed in sweet potato slices, indicating a potential protective effect. The whole genome of MEPS155 was characterized by a size of 8,030,375 bp, encompassing 7234 coding DNA sequences and 32 secondary metabolite biosynthetic gene clusters. Transcriptomic analysis revealed 1869 differentially expressed genes in the treated group that cultured with C. fimbriata, notably influencing pathways associated with porphyrin metabolism, fatty acid biosynthesis, and biosynthesis of type II polyketide products. These alterations in gene expression are hypothesized to be linked to the production of secondary metabolites contributing to the inhibition of C. fimbriata. Metabolomic analysis identified 1469 potential differently accumulated metabolites (PDAMs) when comparing MEPS155 and the control group. The up-regulated PDAMs were predominantly associated with the biosynthesis of various secondary metabolites, including vanillin, myristic acid, and protocatechuic acid, suggesting potential inhibitory effects on plant pathogenic fungi. Our study underscores the ability of strain S. djakartensis MEPS155 to inhibit C. fimbriata growth through the production of secretory enzymes or secondary metabolites. The findings contribute to a theoretical foundation for future investigations into the role of MEPS155 in postharvest black rot prevention in sweet potato.

Asprosin promotes vascular inflammation via TLR4-NFκB-mediated NLRP3 inflammasome activation in hypertension.

Objective: and design Mild vascular inflammation promotes the pathogenesis of hypertension. Asprosin, a newly discovered adipokine, is closely associated with metabolic diseases. We hypothesized that asprosin might led to vascular inflammation in hypertension via NLRP3 inflammasome formation. This study shows the importance of asprosin in the vascular inflammation of hypertension. Methods: Primary vascular smooth muscle cells (VSMCs) were obtained from the aorta of animals, including spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), NLRP3-/- and wild-type mice. Studies were performed in VSMCs in vitro, as well as WKY and SHR in vivo. Results: Asprosin expressions were up-regulated in VSMCs and media of arteries in SHR. Asprosin overexpression promoted NLRP3 inflammasome activation via Toll-like receptor 4 (TLR4), accompanied with activation of NFκB signaling pathway in VSMCs. Exogenous asprosin protein showed similar roles in promoting NLRP3 inflammasome activation. Knockdown of asprosin restrained NLRP3 inflammasome and p65-NFκB activation in VSMCs of SHR. NLRP3 inhibitor MCC950 or NFκB inhibitor BAY11-7082 attenuated asprosin-caused VSMC proliferation and migration. Asprosin-induced interleukin-1ß production, proliferation and migration were attenuated in NLRP3-/- VSMCs. Local asprosin knockdown in common carotid artery of SHR attenuated inflammation and vascular remodeling. Conclusions: Asprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.

Chemical reaction steers spatiotemporal self-assembly of supramolecular hydrogels.

Supramolecular structures are widespread in living system, which are usually spatiotemporally regulated by sophisticated metabolic processes to enable vital biological functions. Inspired by living system, tremendous efforts have been made to realize spatiotemporal control over the self-assembly of supramolecular materials in synthetic scenario by coupling chemical reaction with molecular self-assembly process. In this review, we focused on the works related to supramolecular hydrogels that are regulated in space and time using chemical reaction. Firstly, we summarized how spatially controlled self-assembly of supramolecular hydrogels can be achieved via chemical reaction-instructed self-assembly, and the application of such a self-assembly methodology in biotherapy was discussed as well. Second, we reviewed dynamic supramolecular hydrogels dictated by chemical reaction networks that can evolve their structures and properties against time. Third, we discussed the recent progresses in the control of the self-assembly of supramolecular hydrogels in both space and time though a reaction-diffusion-coupled self-assembly approach. Finally, we provided a perspective on the further development of spatiotemporally controlled supramolecular hydrogels using chemical reaction in the future.

Ecological effect of microplastics on soil microbe-driven carbon circulation and greenhouse gas emission: A review.

Soil organic carbon (SOC) pool, the largest part of terrestrial ecosystem, controls global terrestrial carbon balance and consequently presented carbon cycle-climate feedback in climate projections. Microplastics, (MPs, <5 mm) as common pollutants in soil ecosystems, have an obvious impact on soil-borne carbon circulation by affecting soil microbial processes, which play a central role in regulating SOC conversion. In this review, we initially presented the sources, properties and ecological risks of MPs in soil ecosystem, and then the differentiated effects of MPs on the component of SOC, including dissolved organic carbon, soil microbial biomass carbon and easily oxidized organic carbon varying with the types and concentrations of MPs, the soil types, etc. As research turns into a broader perspective, greenhouse gas emissions dominated by the mineralization of SOC coming into view since it can be significantly affected by MPs and is closely associated with soil microbial respiration. The pathways of MPs impacting soil microbes-driven carbon conversion include changing microbial community structure and composition, the functional enzyme's activity and the abundance and expression of functional genes. However, numerous uncertainties still exist regarding the microbial mechanisms in the deeper biochemical process. More comprehensive studies are necessary to explore the affected footprint and provide guidance for finding the evaluation criterion of MPs affecting climate change.

Neural activation signatures in individuals with subclinical depression: A task-fMRI meta-analysis.

BACKGROUND: Previous task-related functional magnetic resonance imaging (task-fMRI) investigations have documented abnormal brain activation associated with subclinical depression (SD), defined as a clinically relevant level of depressive symptoms that does not meet the diagnostic criteria for major depressive disorder. However, these task-fMRI studies have not reported consistent conclusions. Performing a voxel-based meta-analysis of task-fMRI studies may yield reliable findings. METHODS: We extracted the peak coordinates and t values of included studies and analyzed brain activation between individuals with SD and healthy controls (HCs) using anisotropic effect-size signed differential mapping (AES-SDM). RESULTS: A systematic literature search identified eight studies, including 266 individuals with SD and 281 HCs (aged 14 to 25). The meta-analysis showed that individuals with SD exhibited significantly greater activation in the right lenticular nucleus and putamen according to task-fMRI. The meta-regression analysis revealed a negative correlation between the proportion of females in a group and activation in the right striatum. LIMITATIONS: The recruitment criteria for individuals with SD, type of tasks and MRI acquisition parameters of included studies were heterogeneous. The results should be interpreted cautiously due to insufficient included studies. CONCLUSION: Our findings suggest that individuals with SD exhibit increased activation in the right lenticular nucleus, putamen and striatum, which may indicate a compensatory increase in response to an impairment of insular and striatal function caused by depression. These results provide valuable insights into the potential pathophysiology of brain dysfunction in SD.

Mechanism Analysis of OsZF8-Mediated Regulation of Rice Resistance to Sheath Blight.

Transcription factors are key molecules involved in transcriptional and post-transcriptional regulation in plants and play an important regulatory role in resisting biological stress. In this study, we identified a regulatory factor, OsZF8, mediating rice response to Rhizoctonia solani (R. solani) AG1-IA infection. The expression of OsZF8 affects R. solani rice infection. OsZF8 knockout and overexpressed rice plants were constructed, and the phenotypes of mutant and wild-type (WT) plants showed that OsZF8 negatively regulated rice resistance to rice sheath blight. However, it was speculated that OsZF8 plays a regulatory role at the protein level. The interacting protein PRB1 of OsZF8 was screened using the yeast two-hybrid and bimolecular fluorescence complementation test. The results showed that OsZF8 effectively inhibited PRB1-induced cell death in tobacco cells, and molecular docking results showed that PRB1 had a strong binding effect with OsZF8. Further, the binding ability of OsZF8-PRB1 to ergosterol was significantly reduced when compared with the PRB1 protein. These findings provide new insights into elucidating the mechanism of rice resistance to rice sheath blight.

Discovery and biological evaluation of biaryl acetamide derivatives as selective and in vivo active sphingosine kinase-2 inhibitors.

Sphingosine kinase 2 (SphK2) has emerged as a promising target for cancer therapy due to its critical role in tumor growth. However, the lack of potent and selective inhibitors has hindered its clinical application. Herein, we report the design and synthesis of a series of novel SphK2 inhibitors, culminating in the identification of compound 12q as a highly selective and potent inhibitor of SphK2. Molecular dynamics simulations suggest that the incorporation of larger substitution groups facilitates a more effective occupation of the binding site, thereby stabilizing the complex. Compared to the widely used inhibitor ABC294640, compound 12q exhibits superior anti-proliferative activity against various cancer cells, inducing G2 phase arrest and apoptosis in liver cancer cells HepG2. Notably, 12q inhibited migration and colony formation in HepG2 and altered intracellular sphingolipid content. Moreover, intraperitoneal administration of 12q in mice resulted in decreased levels of S1P. 12q provides a valuable tool compound for exploring the therapeutic potential of targeting SphK2 in cancer.

Intestinal persistence of Bifidobacterium infantis is determined by interaction of host genetics and antibiotic exposure.

Probiotics have gained significant attention as a potential strategy to improve health by modulating host-microbe interactions, particularly in situations where the normal microbiota has been disrupted. However, evidence regarding their efficacy has been inconsistent, with considerable interindividual variability in response. We aimed to explore whether a common genetic variant that affects the production of mucosal α(1,2)-fucosylated glycans, present in around 20% of the population, could explain the observed interpersonal differences in the persistence of commonly used probiotics. Using a mouse model with varying α(1,2)-fucosylated glycans secretion (Fut2WT or Fut2KO), we examined the abundance and persistence of Bifidobacterium strains (infantis, breve, and bifidum). We observed significant differences in baseline gut microbiota characteristics between Fut2WT and Fut2KO littermates, with Fut2WT mice exhibiting enrichment of species able to utilize α(1,2)-fucosylated glycans. Following antibiotic exposure, only Fut2WT animals showed persistent engraftment of Bifidobacterium infantis, a strain able to internalize α(1,2)-fucosylated glycans, whereas B. breve and B. bifidum, which cannot internalize α(1,2)-fucosylated glycans, did not exhibit this difference. In mice with an intact commensal microbiota, the relationship between secretor status and B. infantis persistence was reversed, with Fut2KO animals showing greater persistence compared to Fut2WT. Our findings suggest that the interplay between a common genetic variation and antibiotic exposure plays a crucial role in determining the dynamics of B. infantis in the recipient gut, which could potentially contribute to the observed variation in response to this commonly used probiotic species.

Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation.

The role of tumor-resident microbiota in modulating tumor immunity remains unclear. Here, we discovered an abundance of intra-tumoral bacteria, such us E.coli, residing and resulting in Colorectal cancer liver metastasis (CRLM). E.coli enhanced lactate production, which mediated M2 macrophage polarization by suppressing nuclear factor-κB -gene binding (NF-κB) signaling through retinoic acid-inducible gene 1 (RIG-I) lactylation. Lactylation of RIG-I suppressed recruitment of NF-κB to the Nlrp3 promoter in macrophages, thereby reducing its transcription. This loss of Nlrp3 affected the immunosuppressive activities of regulatory T cells (Tregs) and the antitumor activities of and CD8+ T cells. Small-molecule compound screening identified a RIG-I lactylation inhibitor that suppressed M2 polarization and sensitized CRLM to 5-fluorouracil (5-FU). Our findings suggest that tumor-resident microbiota may be a potential target for preventing and treating CRLM.

A C-H functionalization approach to diverse nitrogenous scaffolds through conjugate addition of catalytic allyliron nucleophiles.

Cyclopentadienyliron(ii) dicarbonyl complexes capable of coordinating to and enhancing the acidity of a range of unsaturated substrates have emerged as a new class of base-metal derived catalysts for C-H functionalization. In this manuscript, the iron-catalyzed C-H functionalization of allylic C(sp3)-H bonds using nitrogen containing α,ß-unsaturated carbonyl compounds as coupling partners is reported. Employing a cationic cyclopentadienyliron dicarbonyl complex, this redox neutral process converts simple alkenes into allylic anion equivalents for 1,4-addition into maleimides, acyclic α,ß-unsaturated imides, and vinylogous amides. The judicious pairing of pyridine and alkylamine bases with Lewis acid additives allowed each of these classes of substrates to be successfully employed, allowing for the formation of a diverse collection of cyclic and acyclic nitrogen-containing compounds featuring C-C unsaturation. The resulting Michael adducts can be further transformed into a variety of useful scaffolds such as allylated pyrroles, pyrrolidines, and carbocyclic acids.

Portable Triboelectric Electrostatic Tweezer for External Manipulation of Droplets within a Closed Femtosecond Laser-Treated Superhydrophobic System.

Controllable droplet manipulation has diverse applications; however, limited methods exist for externally manipulating droplets in confined spaces. Herein, we propose a portable triboelectric electrostatic tweezer (TET) by integrating electrostatic forces with a superhydrophobic surface that can even manipulate droplets in an enclosed space. Electrostatic induction causes the droplet to be subjected to an electrostatic force in an electrostatic field so that the droplet can be moved freely with the TET on a superhydrophobic platform. Characterized by its high precision, flexibility, and robust binding strength, TET can manipulate droplets under various conditions and achieve a wide range of representative fluid applications such as droplet microreactors, precise self-cleaning, cargo transportation, the targeted delivery of chemicals, liquid sorting, soft droplet robotics, and cell labeling. Specifically, TET demonstrated the ability to manipulate internal droplets from the outside of a closed system, such as performing cell labeling experiments within a sealed Petri dish without opening the culture system.