Araloside A alleviates sepsis-induced acute lung injury via PHD2/HIF-1α in macrophages.

BACKGROUND: Acute lung injury (ALI)-induced acute respiratory syndromes is a critical pathological sequala of sepsis. Araloside A (ARA), extracted from Aralia taibaiensis, possesses anti-oxidative and pro-apoptotic effects, as well as a protective effect against inflammatory diseases such as gastric ulcers. However, its impact on progression of ALI remains unknown. This study seeks to assess the therapeutic effect of ARA in sepsis-induced ALI, and to elucidate the underlying mechanism. METHODS: Sepsis-induced ALI was induced in C57BL/6 mice using lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) along with simultaneous administration of ARA. In vitro, bone marrow-derived macrophages (BMDMs) and RAW264.7 cells were exposed to LPS to activate proinflammatory macrophages in the presence/absence of ARA. RNA sequencing of BMDMs was then conducted to elucidate the detailed mechanism. RESULTS: Treatment of mice with ARA led to a significant reduction in serum level of inflammatory cytokines, ameliorated sepsis-induced ALI (i.e., impaired barrier integrity, cell apoptosis), and increased survival of septic mice. In vitro, ARA effectively inhibited activation of proinflammatory BMDMs. In addition, RNA sequencing revealed that the PHD2/HIF-1α signaling played a critical role in the anti-inflammatory effects of ARA. ARA suppressed proinflammatory macrophages to ameliorate lung inflammation in septic mice by restoring PHD2/HIF-1α signaling. CONCLUSIONS: ARA prevented mice from the fatal effects of sepsis by restoring PHD2/HIF-1α signaling, thereby inhibiting activation of proinflammatory macrophages. These findings suggest that ARA could be a promising therapy for sepsis-induced ALI.

Methanogenic Potential of Sewer Microbiomes and Its Implications for Methane Emission.

The sewer system, despite being a significant source of methane emissions, has often been overlooked in current greenhouse gas inventories due to the limited availability of quantitative data. Direct monitoring in sewers can be expensive or biased due to access limitations and internal heterogeneity of sewer networks. Fortunately, since methane is almost exclusively biogenic in sewers, we demonstrate in this study that the methanogenic potential can be estimated using known sewer microbiome data. By combining data mining techniques and bioinformatics databases, we developed the first data-driven method to analyze methanogenic potentials using a data set containing 633 observations of 53 variables obtained from literature mining. The methanogenic potential in the sewer sediment was around 250-870% higher than that in the wet biofilm on the pipe and sewage water. Additionally, k-means clustering and principal component analysis linked higher methane emission rates (9.72 ± 51.3 kgCO2 eq m-3 d-1) with smaller pipe size, higher water level, and higher potentials of sulfate reduction in the wetted pipe biofilm. These findings exhibit the possibility of connecting microbiome data with biogenic greenhouse gases, further offering insights into new approaches for understanding greenhouse gas emissions from understudied sources.

Nanozyme coating-gated multifunctional COF composite based dual-ratio enhanced dual-mode sensor for highly sensitive and reliable detection of organophosphorus pesticides in real samples.

The reliable detection of organophosphorus pesticides (OPs) in complex matrices remains an enormous challenge due to inevitable interference of sample matrices and testing factors. To address this issue, we designed a nanozyme-coated mesoporous COF with guest molecule loading, and successfully used it to construct a dual-ratio dual-mode sensor through target-regulated signal generation. The multifunctional COF-based composite (MB/COF@MnO2, MCM) featured high loading of methylene blue (MB), oxidase-like MnO2 coatings as gatekeepers, and specific recognition of thiocholine (TCh). TCh, a regulator produced from acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine, could decompose MnO2 coatings, triggering the release of abundant MB and oxidation of few o-phenylenediamine (OPD). OPs, strong inhibitors of AChE, could restrain TCh production and MnO2 decomposition, thereby controlling the release of less MB and oxidation of more OPD. This regulation boosted the dual-ratio dual-mode assay of OPs by using the released MB and oxidized OPD in the solution as testing signals, measured by both fluorescent and electrochemical methods. Experimental results demonstrated the sensitive detection of dichlorvos with LODs of 0.083 and 0.026 ng/mL via the fluorescent/electrochemical mode, respectively. This study represented a creative endeavor to develop dual-ratio dual-mode sensors for OPs detection in complex samples, offering high sensitivity, excellent selectivity, and good reliability.

Custom microfluidic chip design enables cost-effective three-dimensional spatiotemporal transcriptomics with a wide field of view.

Spatial transcriptomic techniques offer unprecedented insights into the molecular organization of complex tissues. However, integrating cost-effectiveness, high throughput, a wide field of view and compatibility with three-dimensional (3D) volumes has been challenging. Here we introduce microfluidics-assisted grid chips for spatial transcriptome sequencing (MAGIC-seq), a new method that combines carbodiimide chemistry, spatial combinatorial indexing and innovative microfluidics design. This technique allows sensitive and reproducible profiling of diverse tissue types, achieving an eightfold increase in throughput, minimal cost and reduced batch effects. MAGIC-seq breaks conventional microfluidics limits by enhancing barcoding efficiency and enables analysis of whole postnatal mouse sections, providing comprehensive cellular structure elucidation at near single-cell resolution, uncovering transcriptional variations and dynamic trajectories of mouse organogenesis. Our 3D transcriptomic atlas of the developing mouse brain, consisting of 93 sections, reveals the molecular and cellular landscape, serving as a valuable resource for neuroscience and developmental biology. Overall, MAGIC-seq is a high-throughput, cost-effective, large field of view and versatile method for spatial transcriptomic studies.

Iron and Nickel Substituted Perovskite Cobaltites for Sustainable Oxygen Evolving Anodes in Alkaline Environment.

Perovskite oxides have great flexibility in their elemental composition, which is accompanied by large adjustability in their electronic properties. Herein, we synthesized twelve perovskites oxide-based catalysts for the oxygen evolution reaction (OER) in alkaline media. The catalysts are based on the parent oxide perovskite Ba0.5Gd0.8La0.7Co2O6-δ (BGLC587) and are synthesized through the sol-gel citrate synthesis route. To reduce the demand on cobalt (Co), but also increase the intrinsic catalytic activity of BGLC587 for the OER, we substitute Co on the B-site with certain amounts of Fe and Ni, synthesizing catalysts of the general formula Ba0.5Gd0.8La0.7Co2-x-yFexNiyO6-δ. A plethora of physicochemical and electrochemical methods suggest that an Fe content between 30% and 70% increases the intrinsic catalytic activity of BGLC587, while Tafel slopes in combination with in-situ Raman spectroscopy suggest the rate determining step is likely a proton-exchange reaction, progressing possibly through the lattice oxygen mechanism (LOM). We apply one of the optimized, Co-substituted perovskites in a monolithic, photovoltaic (PV)-driven electrolysis cell and we achieve an initial solar-to-hydrogen (STH) conversion efficiency of 10.5% under one sun solar simulated illumination.

Inhibition of heme-thiolate monooxygenase CYP1B1 prevents hepatic stellate cell activation and liver fibrosis by accumulating trehalose.

Activation of extracellular matrix-producing hepatic stellate cells (HSCs) is a key event in liver fibrogenesis. We showed that the expression of the heme-thiolate monooxygenase cytochrome P450 1B1 (CYP1B1) was elevated in human and mouse fibrotic livers and activated HSCs. Systemic or HSC-specific ablation and pharmacological inhibition of CYP1B1 attenuated HSC activation and protected male but not female mice from thioacetamide (TAA)-, carbon tetrachloride (CCl4)-, or bile duct ligation (BDL)-induced liver fibrosis. Metabolomic analysis revealed an increase in the disaccharide trehalose in CYP1B1-deficient HSCs resulting from intestinal suppression of the trehalose-metabolizing enzyme trehalase, whose gene we found to be a target of RARα. Trehalose or its hydrolysis-resistant derivative lactotrehalose exhibited potent antifibrotic activity in vitro and in vivo by functioning as an HSC-specific autophagy inhibitor, which may account for the antifibrotic effect of CYP1B1 inhibition. Our study thus reveals an endobiotic function of CYP1B1 in liver fibrosis in males, mediated by liver-intestine cross-talk and trehalose. At the translational level, pharmacological inhibition of CYP1B1 or the use of trehalose/lactotrehalose may represent therapeutic strategies for liver fibrosis.

Molybdenum and Vanadium-Codoped Cobalt Carbonate Nanosheets Deposited on Nickel Foam as a High-Efficient Bifunctional Catalyst for Overall Alkaline Water Splitting.

To address issues of global energy sustainability, it is essential to develop highly efficient bifunctional transition metal-based electrocatalysts to accelerate the kinetics of both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). Herein, the heterogeneous molybdenum and vanadium codoped cobalt carbonate nanosheets loaded on nickel foam (VMoCoCOx@NF) are fabricated by facile hydrothermal deposition. Firstly, the mole ratio of V/Mo/Co in the composite is optimized by response surface methodology (RSM). When the optimized composite serves as a bifunctional catalyst, the water-splitting current density achieves 10 mA cm-2 and 100 mA cm-2 at cell voltages of 1.54 V and 1.61 V in a 1.0 M KOH electrolyte with robust stability. Furthermore, characterization is carried out using field emission scanning electron microscopy-energy dispersive spectroscopy (FESEM-EDS), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Density functional theory (DFT) calculations reveal that the fabricated VMoCoCOx@NF catalyst synergistically decreases the Gibbs free energy of hydrogen and oxygen-containing intermediates, thus accelerating OER/HER catalytic kinetics. Benefiting from the concerted advantages of porous NF substrates and clustered VMoCoCOx nanosheets, the fabricated catalyst exhibits superior electrocatalytic performance. This work presents a novel approach to developing transition metal catalysts for overall water splitting.

A Minimalist Pathogen-Like Sugar Nanovaccine for Enhanced Cancer Immunotherapy.

Pathogen-mimicking nanoparticles have emerged at the forefront of vaccine delivery technology, offering potent immune activation and excellent biocompatibility. Among these innovative carriers, mannan, a critical component of yeast cell walls, shows promise as an exemplary vaccine carrier. Nevertheless, it faces challenges like unpredictable immunogenicity, rapid elimination, and limited antigen loading due to high water solubility. Herein, mannan with varying carbon chain ratios is innovatively modified, yielding a series of dodecyl chains modified mannan (Mann-C12). Through meticulous screening, a mannan variant with a 40% grafting ratio is pinpointed as the optimal vaccine carrier. Further RNA sequencing confirms that Mann-C12 exhibits desired immunostimulatory characteristics. Coupled with antigen peptides, Mann-C12/OVA257-280 nanovaccine initiates the maturation of antigen-presenting cells by activating the TLR4 and Dectin-2 pathways, significantly boosting antigen utilization and sparking antigen-specific immune responses. In vivo, experiments utilizing the B16-OVA tumor model underscore the exceptional preventive capabilities of Mann-C12/OVA257-280. Notably, when combined with immune checkpoint blockade therapy, it displays a profound synergistic effect, leading to marked inhibition of tumor growth. Thus, the work has yielded a pathogen-like nanovaccine that is both simple to prepare and highly effective, underscoring the vast potential of mannan-modified nanovaccines in the realm of cancer immunotherapy.

Oxygen electrocatalysis-driven electrochemiluminescence by hierarchical carbon nanoflower-supported copper-modulated cobalt sulfide for cytosensing.

A facile cation modulation strategy is proposed for the synthesis of copper/cobalt bimetallic sulfides dispersed on hierarchical carbon nanoflowers, which exhibit excellent oxygen electrocatalysis capacity to drive electrochemiluminescence for cytosensing.

Computational investigation of stochastic Zika virus optimal control model using Legendre spectral method.

This study presents a computational investigation of a stochastic Zika virus along with optimal control model using the Legendre spectral collocation method (LSCM). By accumulation of stochasticity into the model through the proposed stochastic differential equations, we appropriating the random fluctuations essential in the progression and disease transmission. The stability, convergence and accuracy properties of the LSCM are conscientiously analyzed and also demonstrating its strength for solving the complex epidemiological models. Moreover, the study evaluates the various control strategies, such as treatment, prevention and treatment pesticide control, and identifies optimal combinations that the intervention costs and also minimize the proposed infection rates. The basic properties of the given model, such as the reproduction number, were determined with and without the presence of the control strategies. For R 0 < 0 , the model satisfies the disease-free equilibrium, in this case the disease die out after some time, while for R 0 > 1 , then endemic equilibrium is satisfied, in this case the disease spread in the population at higher scale. The fundamental findings acknowledge the significant impact of stochastic phonemes on the robustness and effectiveness of control strategies that accelerating the need for cost-effective and multi-faceted approaches. In last the results provide the valuable insights for public health department to enabling more impressive mitigation of Zika virus outbreaks and management in real-world scenarios.

How local electric field regulates C-C coupling at a single nanocavity in electrocatalytic CO2 reduction.

C-C coupling is of utmost importance in the electrocatalytic reduction of CO2, as it governs the selectivity of diverse product formation. Nevertheless, the difficulties to directly observe C-C coupling pathways at a specific nanocavity hinder the advances in catalysts and electrolyzer design for efficient high-value hydrocarbon production. Here we develop a nano-confined Raman technology to elucidate the influence of the local electric field on the evolution of C-C coupling intermediates. Through precise adjustments to the Debye length in nanocavities of a copper catalyst, the overlapping of electrical double layers drives a transition in the C-C coupling pathway at a specific nanocavity from *CHO-*CO coupling to the direct dimerization of *CO species. Experimental evidence and simulations validate that a reduced potential drop across the compact layer promotes a higher yield of CO and promotes the direct dimerization of *CO species. Our findings provide insights for the development of highly selective catalyst materials tailored to promote specific products.

Photo-triggered AuAg@g-C3N4 composite nanoplatform for multimodal broad-spectrum antibacterial therapy.

Strategies based on nanomaterials for sterilization address the problem of antibiotic resistance faced by conventional antimicrobials, with the contribution of photocatalytic compounds being particularly prominent. Herein, to integrate multiple bactericidal techniques into a system for generating synergistic antibacterial effects, a novel photo-triggered AuAg@g-C3N4 composite nanoplatform was constructed by anchoring AuAg on the surface of a g-C3N4 layer. As the composite nanoplatform had a lower bandgap and superior visible light utilization efficiency, it could facilitate free electron transfer better and exhibit superior photocatalytic activity under light conditions. Moreover, the AuAg@g-C3N4 composite nanoplatform integrated the bactericidal modes of silver ion toxicity, physical disruption of bacterial cell membranes by the multilayer structure, and excellent photocatalytic activity, exhibiting extremely superior bactericidal effects against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis, with a bactericidal efficiency of up to 100%.

Excited-Ground-State Transition of the RNA Strand Slippage Mechanism Captured by the Base-Specific Force Field.

Excited-ground-state transition and strand slippage of RNA play key roles in transcription and translation of central dogma. Due to limitation of current experimental techniques, the dynamic structure ensembles of RNA remain inadequately understood. Molecular dynamics simulations offer a promising complementary approach, whose accuracy depends on the force field. Here, we develop the new version of RNA base-specific force field (BSFF2) to address underestimation of base pairing stability and artificial backbone conformations. Extensive evaluations on typical RNA systems have comprehensively confirmed the accuracy of BSFF2. Furthermore, BSFF2 demonstrates exceptional efficiency in de novo folding of tetraloops and reproducing base pair reshuffling transition between RNA excited and ground states. Then, we explored the RNA strand slippage mechanism with BSFF2. We conducted a comprehensive three-dimensional structural investigation into the strand slippage of the most complex r(G4C2)9 repeat element and presented the molecular details in the dynamic transition along with the underlying mechanism. Our results of capturing the strand slippage, excited-ground transition, de novo folding, and simulations for various typical RNA motifs indicate that BSFF2 should be one of valuable tools for dynamic conformation research and structure prediction of RNA, and a future contribution to RNA-targeted drug design as well as RNA therapy development.

Multi-Shell Nanourchin-Integrated Dual Mode Lateral Flow Immunoassay for Sensitive and Rapid Detection of Clinical Cardiac Myosin-Binding Protein C.

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 109, which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.

A "dual-key-and-lock" DNA nanodevice enables spatially controlled multimodal imaging and combined cancer therapy.

DNA-based theragnostic platforms have attracted more and more attention, while their applications are still impeded by nonspecific interference and insufficient therapeutic efficacy. Herein, we fabricate an integrated "dual-key-and-lock" DNA nanodevice (DKL-DND) which is composed of the inner Dox/Hairpin/Aptazyme-Au@Ag@Au probes and the outer metal-organic frameworks loaded with Fuel strand. Once internalized into human breast cancer cells (MCF-7), the DKL-DND is activated by cascaded endogenous stimuli (acidic pH in the lysosome and high expression of ATP in the cytoplasm), leading to spatially controlled optical/magnetic resonance multimodal imaging and gene/chemo/small molecule combined cancer therapy. By engineering pH and ATP-responsive units as cascaded locks on the DKL-DND, the operating status of the nanodevice and accessibility of encapsulated anti-tumour drugs can be precisely regulated in the specified physiological states, avoiding the premature activation and release during assembly and delivery. Both in vitro and in vivo assessments demonstrate that the DKL-DND with excellent stimuli-responsive ability, biocompatibility, stability and accumulation behaviour was capable of simultaneously affording accurate tumour diagnosis and efficient tumour growth inhibition. This integrated DKL-DND exhibits great promise in constructing self-adaptive nanodevices for multimodal imaging-guided combination therapy.

91-month follow-up of solitary punctate chorioretinitis in a Chinese patient.

BACKGROUND: Solitary Punctate Chorioretinitis (SPC) is a recently identified form of punctate inner choroidopathy (PIC) characterized by a single lesion in the fovea of the macula. Previous studies with a maximum follow-up of 48 months were insufficient. Our review uncovered a case sustained for 91 months. CASE PRESENTATION: A 28-year-old young woman experienced with sudden visual loss in her right eye. Comprehensive examinations, including assessment of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, noncontact tonometry, fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), optical coherence tomography angiography (OCTA), perimetry, and microperimetry, were conducted. Over 91 months, the lesion slightly enlarged, remained yellow-white and punctate, and stayed in the central macula of the posterior pole. OCT images depicted subsidence in the inner nuclear layer (INL), the outer plexiform layer (OPL), photoreceptor layer, and disruption of the external limiting membrane (ELM), ellipsoid zone, and retinal pigment epithelium (RPE)/Bruch's membrane complex. Retinal herniation, focal choroidal excavation (FCE), and abnormal vessels in the choriocapillaris were noted. At the slab of the choriocapillaris, OCTA demonstrated that the lesion resembled a linear vascular structure, distinct from the structure of normal choriocapillaris. This confirmed the lesion as an abnormal vascular formation. FAF revealed a punctate hypo-autofluorescence lesion and abnormal hyper-autofluorescence near the optic disc and macula. FFA demonstrated a punctate hyper-fluorescent lesion inferotemporal to the fovea. The vascular structure remained stable without fluid exudation on OCT images, hence anti-vascular endothelial growth factor (anti-VEGF) treatment was not administered. Visual acuity improved from counting fingers to 0.07 in 52 days, reached 0.6 after 15 months, remained at 0.6 from 56 to 80 months, and returned to 0.8 after 91 months, although accompanied by local scotomas. The lesion pattern slightly enlarged without scarring. CONCLUSIONS: Throughout long-term follow-up, we had long suspected the presence of choroidal neovascularization (CNV) and found the FCE in the last visit. Eventually, we concluded that SPC could potentially constitute a distinct subtype of PIC. The patient received no treatment, and vision recovered to 0.8. If CNV is suspected in SPC, anti-VEGF treatment may not be necessary without activity on OCT, but close monitoring is essential.

Bioinspired molecule-functionalized Cu with high CO adsorption for efficient CO electroreduction to acetate.

Electrochemical reduction of carbon dioxide (CO2) or carbon monoxide (CO) to valuable multi-carbon (C2+) products like acetate is a promising approach for a sustainable energy economy. However, it is still challenging to achieve high activity and selectivity for acetate production, especially in neutral electrolytes. Herein, a bioinspired hemin/Cu hybrid catalyst was developed to enhance the surface *CO coverage for highly efficient electroreduction of CO to acetate fuels. The hemin/Cu electrocatalyst exhibits a remarkable faradaic efficiency of 45.2% for CO-to-acetate electroreduction and a high acetate partial current density of 152.3 mA cm-2. Furthermore, the developed hybrid catalyst can operate stably at 200 mA cm-2 for 14.6 hours, producing concentrated acetate aqueous solutions (0.235 M, 2.1 wt%). The results of in situ Raman spectroscopy and theoretical calculations proved that the Fe-N4 structure of hemin could enhance the CO adsorption and enrich the local concentration of CO, thereby improving C-C coupling for acetate production. In addition, compared to the unmodified Cu catalysts, the Cu catalysts functionalized with cobalt phthalocyanine with a Co-N4 structure also exhibit improved acetate performance, proving the universality of this bioinspired molecule-enhanced strategy. This work paves a new way to designing bioinspired electrolysis systems for producing specific C2+ products from CO2 or CO electroreduction.

The effects of nanoplastics and microcystin-LR coexposure on Aristichthys nobilis at the early developmental stages.

Nanoplastics (NPs) and microcystin-LR (MC-LR) are two common and harmful pollutants in water environments, especially at aquafarm where are full of plastic products and algae. It is of great significance to study the toxic effects and mechanisms of the NPs and/or MC-LR on fish at the early stage. In this study, the embryo and larvae of a filtering-feeding fish, Aristichthys nobilis, were used as the research objects. The results showed that the survival and hatching rates of the embryo were not significantly affected by the environmental concentration exposure of these two pollutants. Scanning electron microscopy (SEM) observation displayed that NPs adhered to the surface of the embryo membrane. Transcriptomic and bioinformatic analyses revealed that the NPs exposure activated neuromuscular junction development and skeletal muscle fiber in larvae, and affected C5-Branched dibasic acid metabolism. The metabolic and biosynthetic processes of zeaxanthin, xanthophyll, tetraterpenoid, and carotenoid were suppressed after the MC-LR exposure, which was harmful to the retinol metabolism of fish. Excessive production of superoxide dismutase (SOD) was detected under the MC-LR exposure. The MC-LR and NPs coexposure triggered primary immunodeficiency and adaptive immune response, leading to the possibility of reduced fitness of A.nobilis during the development. Collectively, our results indicate that environmental concentration NPs and MC-LR coexposure could cause toxic damage and enhance sick risk in A.nobilis, providing new insights into the risk of NPs and MC-LR on filtering-feeding fish.