A General Molecular Structural Design for Highly Efficient Photopyroptosis that can be Activated within 10 s Irradiation.

Photopyroptosis is an emerging research branch of photodynamic therapy (PDT), whereas there remains a lack of molecular structural principles to fabricate photosensitizers for triggering a highly efficient pyroptosis. Herein, a general and rational structural design principle to implement this hypothesis, is proposed. The principle relies on the clamping of cationic moieties (e.g., pyridinium, imidazolium) onto one photosensitive core to facilitate a considerable mitochondrial targeting (both of the inner and the outer membranes) of the molecules, thus maximizing the photogenerated reactive oxygen species (ROS) at the specific site to trigger the gasdermin E-mediated pyroptosis. Through this design, the pyroptotic trigger can be achieved in a minimum of 10 s of irradiation with a substantially low light dosage (0.4 J cm⁻2), compared to relevant work reported (up to 60 J cm⁻2). Moreover, immunotherapy with high tumor inhibition efficiency is realized by applying the synthetic molecules alone. This structural paradigm is valuable for deepening the understanding of PDT (especially the mitochondrial-targeted PDT) from the perspective of pyroptosis, toward the future development of the state-of-the-art form of PDT.

3D drift correction for super-resolution imaging with a single laser light.

Single-molecule localization microscopy (SMLM) enables three-dimensional (3D) super-resolution imaging of nanoscale structures within biological samples. However, prolonged acquisition introduces a drift between the sample and the imaging system, resulting in artifacts in the reconstructed super-resolution image. Here, we present a novel, to our knowledge, 3D drift correction method that utilizes both the reflected and scattered light from the sample. Our method employs the reflected light of a near-infrared (NIR) laser for focus stabilization while synchronously capturing speckle images to estimate the lateral drift. This approach combines high-precision active compensation in the axial direction with lateral post-processing compensation, achieving the abilities of 3D drift correction with a single laser light. Compared to the popular localization events-based cross correlation method, our approach is much more robust, especially for datasets with sparse localization points.

Constructing Efficient CuAg Nanoalloys on Ce0.90In0.10Oδ for Methanol Deep Oxidation Catalysis at Low Temperature.

So far, it is still extremely challenging to develop an efficient catalyst for deep oxidation of methanol at low temperature. Herein, we report the construction of the highly dispersed CuAg alloy on the surface of Ce0.90In0.10Oδ nanorods support for catalyzing methanol deep oxidation. The composition, structure and properties of catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) spectroscopy and X-ray photoelectron spectroscopy (XPS). The results show that the CuxAg100-x/Ce0.90In0.10Oδ alloy catalysts exhibit superior catalytic activity and stability compared to pure Ag/Ce0.90In0.10Oδ, with the highest activity observed for Cu40Ag60/Ce0.90In0.10Oδ, accompanied by the light-off temperature (T50) and full conversion temperature (T90) of 115 and 145 °C, respectively. This is attributed to the synergistic effect of CuAg alloy, which results in electron transfer, generating more Ag0, and enhanced interaction between CuAg alloy and the support, leading to increased Ce3+ content and higher oxygen vacancy concentration. This work successfully applies CuAg alloy catalysts in thermo-catalytic reaction, offering promising prospects for CuAg alloy catalysts in the methanol deep oxidation.

Emerging Roles of UDP-GalNAc Polypeptide N-Acetylgalactosaminyltransferases in Cardiovascular Disease.

UDP-GalNAc polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) catalyze mucin-type O-glycosylation by transferring α-N-acetylgalactosamine (GalNAc) from UDP-GalNAc to Ser or Thr residues of target proteins. This post-translational modification is common in eukaryotes, yet its biological functions remain unclear. Recent studies have identified specific receptors in the heart and vascular wall cells that can be mucin-type O-glycosylated, and there is now substantial evidence confirming that patients with various cardiovascular diseases (CVDs), such as heart failure, coronary artery disease, myocardial hypertrophy, and vascular calcification, exhibit abnormal changes in GalNAc-Ts. This review aims to highlight recent advances in GalNAc-Ts and their roles in the cardiovascular system, intending to provide evidence for clinical treatment and prevention of CVDs.

pH-responsive on-demand release of eugenol from metal-organic frameworks for synergistic bacterial killing.

Bacterial infections are a big challenge in clinical treatment, making it urgent to develop innovative antibacterial systems and therapies to combat bacterial infections. In this study, we developed a novel MOF-based synergistic antibacterial system (Eu@B-UiO-66/Zn) by loading a natural antibacterial substance (eugenol) with hierarchically porous MOF B-UiO-66 as a carrier and further complexing it with divalent zinc ions. Results indicate that the system achieved a controlled release of eugenol under pH responsive stimulation, with the complexation ability of eugenol and Zn2+ ions as a switch. Due to the destruction of a coordination bond between eugenol and Zn2+ ions by an acidic medium, the release of eugenol loaded in Eu@B-UiO-66/Zn reached 80% at pH 5.8, which was significantly higher than that under pH 8.0 (51%). Moreover, the inhibitory effect of Eu@B-UiO-66/Zn against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) after 24 h was 96.4% and 99.7%, respectively, owing to the synergistic antibacterial effect of eugenol and Zn2+ ions, which was significantly stronger than free eugenol and Eu@B-UiO-66. We hope that this strategy for constructing responsive MOF-based antibacterial carriers could have potential possibilities for the application of MOF materials in antibacterial fields.

PHLDA1 is a P53 target gene involved in P53-mediated cell apoptosis.

Pleckstrin homeolike domain, family A, member 1 (PHLDA1) is a multifunctional protein that plays diverse roles in A variety of biological processes, including cell death, and hence its altered expression has been found in different types of cancer. Although studies have shown a regulatory relationship between p53 and PHLDA1, the molecular mechanism is still unclear. Especially, the role of PHLDA1 in the process of apoptosis is still controversial. In this study, we found that the expression of PHLDA1 in human cervical cancer cell lines was correlated with the up-expression of p53 after treatment with apoptosis-inducing factors. Subsequently, the binding site and the binding effect of p53 on the promoter region of PHLDA1 were verified by our bioinformatics data analysis and luciferase reporter assay. Indeed, we used CRISPR-Cas9 to knockout the p53 gene in HeLa cells and further confirmed that p53 can bind to the promoter region of PHLDA1 gene, and then directly regulate the expression of PHLDA1 by recruiting P300 and CBP to change the acetylation and methylation levels in the promoter region. Finally, a series of gain-of-function experiments further confirmed that p53 re-expression in HeLap53-/- cell can up-regulate the reduction of PHLDA1 caused by p53 knockout, and affect cell apoptosis and proliferation. Our study is the first to explore the regulatory mechanism of p53 on PHLDA1 by using the p53 gene knockout cell model, which further proves that PHLDA1 is a target-gene in p53-mediated apoptosis, and reveals the important role of PHLDA1 in cell fate determination.

Protective effect of arctiin against Toxoplasma gondii HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of cytosolic phospholipase A2 and platelet-activating factor.

Toxoplasma gondii (T. gondii)-derived heat shock protein 70 (T.g.HSP70) is a toxic protein that downregulates host defense responses against T. gondii infection. T.g.HSP70 was proven to induce fatal anaphylaxis in T. gondii infected mice through cytosolic phospholipase A2 (cPLA2) activated-platelet-activating factor (PAF) production via Toll-like receptor 4 (TLR4)-mediated signaling. In this study, we investigated the effect of arctiin (ARC; a major lignan compound of Fructus arctii) on allergic liver injury using T.g.HSP70-stimulated murine liver cell line (NCTC 1469) and a mouse model of T. gondii infection. Localized surface plasmon resonance, ELISA, western blotting, co-immunoprecipitation, and immunofluorescence were used to investigate the underlying mechanisms of action of ARC on T. gondii-induced allergic acute liver injury. The results showed that ARC suppressed the T.g.HSP70-induced allergic liver injury in a dose-dependent manner. ARC could directly bind to T.g.HSP70 or TLR4, interfering with the interaction between these two factors, and inhibiting activation of the TLR4/mitogen-activated protein kinase/nuclear factor-kappa B signaling, thereby inhibiting the overproduction of cPLA2, PAF, and interferon-γ. This result suggested that ARC ameliorates T.g.HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of inflammatory mediators, providing a theoretical basis for ARC therapy to improve T.g.HSP70-induced allergic liver injury.

Cost Analysis of Remote Cardiac Rehabilitation Compared With Facility-Based Cardiac Rehabilitation for Coronary Artery Disease.

Remote cardiac rehabilitation (RCR) represents a promising, noninferior alternative to facility-based cardiac rehabilitation (FBCR). The comparable cost of RCR in US populations has yet to be extensively studied. The purpose of this prospective, patient-selected study of traditional FBCR versus a third-party asynchronous RCR platform was to assess whether RCR can be administered at a comparable cost and clinical efficacy to FBCR. Adult insured patients were eligible for enrollment after an admission for a coronary heart disease event. Patients selected either FBCR or Movn RCR, a 12-week telehealth intervention using an app-based platform and internet-capable medical devices. Clinical demographics, intervention adherence, cost-effectiveness, and hospitalizations at 1-year after enrollment were assessed from the Highmark claims database after propensity matching between groups. A total of 260 patients were included and 171 of those eligible (65.8%) received at least 1 cardiac rehabilitation session and half of the patients chose Movn RCR. The propensity matching produced a sample of 41 matched pairs. Movn RCR led to a faster enrollment and higher completion rates (80% vs 50%). The total medical costs were similar between Movn RCR and FBCR, although tended toward cost savings with Movn RCR ($10,574/patient). The cost of cardiac rehabilitation was lower in those enrolled in Movn RCR ($1,377/patient, p = 0.002). The all-cause and cardiovascular-related hospitalizations or emergency department visits in the year after enrollment in both groups were similar. In conclusion, this pragmatic study of patients after a coronary heart disease event led to equivalent total medical costs and lower intervention costs for an asynchronous RCR platform than traditional FBCR while maintaining similar clinically important outcomes.

An Improved Genetic Algorithm for the Recovery System of USVs Based on Stern Ramp Considering the Influence of Currents.

With the progression of marine exploration and exploitation, as well as the advancements in mechanical intelligence, the utilization of the unmanned surface vehicle (USV) and the design of their guidance system have become prominent areas of focus. However, the stern ramp recovery of the USV is still in its infancy due to its unique attitude requirements and automation design. Furthermore, few studies have addressed the impact of maritime disturbances, with most research limited to simulations. To enhance the efficiency and accuracy of stern ramp recovery, this paper presents the development and construction of a novel recovery system. By incorporating physical modeling of disturbance forces acting on USVs at sea, the practicality of the system is improved. Additionally, an optimized genetic algorithm is introduced in the navigation module to improve convergence rates and subsequently enhance recovery efficiency. A line-of-sight (LOS) algorithm based on average velocity is proposed in this paper to ensure the attainment of unique attitude requirements and to improve the effectiveness of stern chute recovery. This paper provides a detailed description of the independently designed USV hardware system. Moreover, simulations and practical experiments conducted using this experimental platform are presented, offering a new solution for the USV's stern ramp recovery.

A Single Carbon-Dot System Enabling Multiple Stimuli Activated Room-Temperature Phosphorescence.

Room-temperature phosphorescent carbon dots (RTPCDs) have attracted considerable interests due to their unique nanoluminescent characteristic with time resolution. However, it is still a formidable challenge to construct multiple stimuli-activated RTP behaviors on CDs. Since the address of this issue facilitates complex and high-regulatable phosphorescent applications, we here develop a novel strategy to achieve a multiple stimuli responsive phosphorescent activation on a single carbon-dot system (S-CDs), using persulfurated aromatic carboxylic acid as the precursor. The introduction of aromatic carbonyl groups and multiple S atoms can promote the intersystem crossing process to generate RTP characteristic of the produced CDs. Meanwhile, by introducing these functional surface groups into S-CDs, the RTP property can be activated by light, acid, and thermal stimuli in solution or in film state. In this way, multistimuli responsive and tunable RTP characteristics are realized in the single carbon-dot system. Based on this set of RTP properties, S-CDs is applied to photocontrolled imaging in living cells, anticounterfeit label, and multilevel information encryption. Our work will benefit the development of multifunctional nanomaterials together with extending their application scope.

Self-alkali-activated self-cementation achievement and mechanism exploration for the synergistic treatment of the municipal solid waste incineration fly ashes and the arsenic-contaminated soils.

The feasibility and potential mechanisms of the self-alkali activation brought by municipal solid waste incineration (MSWI) fly ashes to the self-cementation of arsenic-contaminated soils were quantitatively evaluated and comprehensively analyzed to avoid the additional application of the alkali activators and binder materials traditionally. The employment of the two kinds of precursor materials achieved the self-alkali-activated self-cementation ('double self') under ambient conditions. The largest compressive strength (MPa) of 25.64 and lowest leaching toxicities (mg/L) of 21.05, 2.86, 0.08, 0.02, 2.05, and 0.34 for Zn, Cu, Cr, Cd, Pb, and As were obtained in the solidified matrix. Geopolymerization kinetics of the 'double self' cementation can be mathematically fitted by the Johnson-Mehl-Avrami-Kolmogorov model. CaClOH and halite in the MSWI fly ashes set up the self-alkali activation by reacting with the kaolinite and quartz in soils contaminated with arsenic by forming layered hydration and three-dimensional geopolymerization products to push for self-cementation.

Synergistic influence of diatomite and MoS2 nanosheets on the self-alkali-activated cementation of the municipal solid waste incineration fly ash and mechanisms.

The solidification/stabilization technique recommended for the disposal of municipal solid waste incineration (MSWI) fly ashes in developed countries was inappropriate for the treatment in most developing counterparts. In this study, the diatomite and MoS2 nanosheets were synergistically employed to activate the self-alkali-activated cementation of the MSWI fly ashes to achieve efficient solidification, the immobilization of heavy metals (HMs), and the inhibition of chloride release. The compressive strength of 28.61 MPa and the leaching toxicities (mg/L) of Zn, Pb, Cu, Cd, and Cr of 2.26, 0.87, 0.5, 0.06, and 0.22 were obtained from the hardened mortars. Diatomite significantly influenced the self-alkali-activated cementation of the MSWI fly ashes while MoS2 nanosheets played both roles in intensifying the stabilization of HMs and strengthening the binding process by inducing the formation of sodalite and kaolinite, enhancing the growth rates of nucleation, and transforming the layered cementation to the partial and full three-dimensional cementation in the hardened matrix. This study not only verified the feasibility of diatomite and MoS2 in activating the self-alkali-activated cementation of the MSWI fly ashes but also supplied a reliable technique for the harmless disposal and efficient utilization of MSWI fly ashes in developing countries.

Self-cementation of gold tailings activated by nonthermal plasma irradiated calcium (hydro)oxide.

The alkalinity of CaO is commonly insufficient in alkali-activating raw soils or minerals for the formation of cementation or geopolymerization. In this study, nonthermal plasma (NTP) irradiation was employed to activate traditional CaO to enhance its efficacy in alkali activation and further intensify the self-cementation of gold tailings. The solidification/stabilization (S/S) of the gold tailings-based matrix activated by NTP-CaO was better than that of CaO. The NTP irradiation enhanced the surface hydroxyl groups and oxygen atoms, decreased the binding energy, formed nanoparticles, and significantly changed the morphologies of the calcium activator. The dosage of the NTP-irradiated CaO (NTP-CaO) directly affected the self-cemented solidification/stabilization of gold tailings. The Johnson-Mehl-Avrami-Kolmogorov model was appropriate for analysing the NTP-CaO-activated geopolymerization kinetics of gold tailings. Three-dimensional (3D) structural minerals covered with small pores were determined in the NTP-CaO-activated cemented samples. The employment of NTP-CaO facilitated the formation of aluminosilicate geopolymers during the self-cementation of gold tailings according to comprehensive characterization strategies. The study achieves the efficient self-remediation of gold tailings by activating calcium precursors, which further solves the contradiction between salinization and alkali activation in the field of noncalcined cementitious materials.

Regulatory effect of moderate Jiang-flavour baijiu (Chinese liquor) dosage on organ function and gut microbiota in mice.

Chinese baijiu, an ancient fermented alcoholic beverage, contains ethanol and a variety of compounds. One of the most popular types of Chinese baijiu is Jiang-flavor baijiu. To investigate the effects of Jiang-flavor baijiu on organ function and gut microbiota, we developed a moderate drinking mouse model and studied its effects on the liver, kidney biomarkers, memory function, and gut microbiota. The results showed that ethanol caused more hepatic steatosis, liver and kidney damage, and memory impairment than Jiang-flavour baijiu consumption. Furthermore, Jiang-flavor baijiu altered the gut microbiota by increasing the abundance of beneficial taxa such as Lactobacillus and Akkermansia, whereas ethanol increased the abundance of harmful bacteria such as Prevotella and Mucispirillum. Our findings provide preliminary evidence that moderate dose Jiang-flavor baijiu regulates gut microbiota and organ function and provide a theoretical foundation for future research on the positive health effects of particular varieties of Chinese baijiu.

Field-dependent deep learning enables high-throughput whole-cell 3D super-resolution imaging.

Single-molecule localization microscopy in a typical wide-field setup has been widely used for investigating subcellular structures with super resolution; however, field-dependent aberrations restrict the field of view (FOV) to only tens of micrometers. Here, we present a deep-learning method for precise localization of spatially variant point emitters (FD-DeepLoc) over a large FOV covering the full chip of a modern sCMOS camera. Using a graphic processing unit-based vectorial point spread function (PSF) fitter, we can fast and accurately model the spatially variant PSF of a high numerical aperture objective in the entire FOV. Combined with deformable mirror-based optimal PSF engineering, we demonstrate high-accuracy three-dimensional single-molecule localization microscopy over a volume of ~180 × 180 × 5 µm3, allowing us to image mitochondria and nuclear pore complexes in entire cells in a single imaging cycle without hardware scanning; a 100-fold increase in throughput compared to the state of the art.

A positive self-amplified H2O2 and acidity circulation for boosting CDT-PTT-starvation therapy.

The therapeutic application of chemodynamic therapy (CDT) is severely limited by the insufficient intracellular H2O2 and acidity in tumor. Herein, an acid-sensitive nanoplatform (ZIF67-ICG/TAM@GOx) to promote H2O2 and acidity enhancement through intracellular cyclic amplification for enhanced CDT is rationally designed. Notably, the acidic conditions of the tumor microenvironment (TME) can turn on the switch of the nanoplatform, setting free the loaded tamoxifen (TAM) and indocyanine green (ICG). The mitochondrial respiration inhibitor TAM and the superoxide dismutase-mimicking ZIF67 synergistically lead to an increase in the content of O2 and H2O2, accelerating the depletion of ß-d-glucose by GOx to generate gluconate and H2O2. The gluconate in turn boosts the acidity to facilitate the collapse of nanoparticles, further significantly promoting the accumulation of intracellular H2O2 through a positive circulation. Consequently, the amplificated endogenous H2O2 is catalyzed by Co2+ to liberate hydroxyl radicals (•OH). Besides, ICG-mediated photothermal therapy (PTT) and GOx-induced starvation therapy along with CDT realize the synergistic cancer treatment. Importantly, in vitro and in vivo experiments verified that the nanoplatform performed superior specificity and excellent therapeutic responses. The smart nanoplatform overcomes H2O2 and acidity deficiency simultaneously for intensive CDT, providing new prospects for the development of biocompatible cancer synergistic therapy strategies.

Promoting Molecular Exchange on Rare-Earth Oxycarbonate Surfaces to Catalyze the Water-Gas Shift Reaction.

It is highly desirable to fabricate an accessible catalyst surface that can efficiently activate reactants and desorb products to promote the local surface reaction equilibrium in heterogeneous catalysis. Herein, rare-earth oxycarbonates (Ln2O2CO3, where Ln = La and Sm), which have molecular-exchangeable (H2O and CO2) surface structures according to the ordered layered arrangement of Ln2O22+ and CO32- ions, are unearthed. On this basis, a series of Ln2O2CO3-supported Cu catalysts are prepared through the deposition precipitation method, which provides excellent catalytic activity and stability for the water-gas shift (WGS) reaction. Density functional theory calculations combined with systematic experimental characterizations verify that H2O spontaneously dissociates on the surface of Ln2O2CO3 to form hydroxyl by eliminating the carbonate through the release of CO2. This interchange efficiently promotes the WGS reaction equilibrium shift on the local surface and prevents the carbonate accumulation from hindering the active sites. The discovery of the unique layered structure provides a so-called "self-cleaning" active surface for the WGS reaction and opens new perspectives about the application of rare-earth oxycarbonate nanomaterials in C1 chemistry.

Combination of Biochar and Functional Bacteria Drives the Ecological Improvement of Saline-Alkali Soil.

The addition of functional bacteria (FB) is low-cost and is widely applied in saline-alkali soil remediation, which may gradually become ineffective due to inter-specific competition with indigenous bacteria. To improve the adaptability of FB, the target FB strains were isolated from local saline-alkali soil, and the combined effects of FB and biochar were explored. The results showed that FB isolated from local soil showed better growth than the purchased strains under high saline-alkali conditions. However, the indigenous community still weakened the function of added FB. Biochar addition provided a specific niche and increased the relative abundance of FB, especially for Proteobacteria and Bacteroidota. As a result, the co-addition of 10% biochar and FB significantly increased the soil available phosphorus (AP) by 74.85% and available nitrogen (AN) by 114.53%. Zea Mays's growth (in terms of height) was enhanced by 87.92% due to the decreased salinity stress and extra nutrients provided.