Development and application of a nitrogen oxides analyzer based on the cavity attenuated phase shift technique.

Nitrogen oxides (NOx) are crucial in tropospheric photochemical ozone (O3) production and oxidation capacity. Currently, the widely used NOx measurement technique is chemiluminescence (CL) (CL-NOx), which tends to overestimate NO2 due to atmospheric oxidation products of NOx (i.e., NOz). We developed and characterized a NOx measurement system using the cavity attenuated phase shift (CAPS) technique (CAPS-NOx), which is free from interferences with nitrogen-containing species. The NOx measured by the CAPS-NOx and CL-NOx analyzers were compared. Results show that both analyzers showed consistent measurement results for NO, but the NO2 measured by the CAPS-NOx analyzer (NO2_CAPS) was mostly lower than that measured by the CL-NOx analyzer (NO2_CL), which led to the deviations in O3 formation sensitivity regime and Ox (= O3 + NO2) sources (i.e., regional background and photochemically produced Ox) determined by the ozone production efficiencies (OPE) calculated from NO2_CL and NO2_CAPS. Overall, OPE_CL exceeded OPE_CAPS by 18.9%, which shifted 3 out of 13 observation days from the VOCs-limited to the transition regime when judging using OPE_CL, as compared to calculations using OPE_CAPS. During the observation period, days dominated by regional background Ox accounted for 46% and 62% when determined using NO2_CL and NO2_CAPS, respectively. These findings suggest that the use of the CL-NOx analyzer tends to underestimate both the VOCs-limited regime and the regional background Ox dominated days. The newly built CAPS-NOx analyzer here can promote the accurate measurement of NO2, which is meaningful for diagnosing O3 formation regimes and Ox sources.

Combining optical genome mapping and RNA-seq for structural variants detection and interpretation in unsolved neurodevelopmental disorders.

BACKGROUND: Structural variations (SVs) are key genetic contributors to neurodevelopmental disorders (NDDs). Exome sequencing (ES), the current first-line tool for genetic testing of NDDs, falls short in SVs detection. This diagnostic gap is being actively addressed by new methods such as optical genome mapping (OGM). METHODS: This study evaluated the utility of combining OGM and RNA-seq in the detection and interpretation of SVs in ES-negative NDDs. OGM was performed in 43 patients with NDDs with inconclusive ES results. Candidate SVs were selected based on disease association and pathogenicity evaluation, and further validated or reconstructed by alternative methods, including long-read sequencing for a complex rearrangement event. RNA-Seq was performed on blood samples from patients with candidate SVs to facilitate interpretation of pathogenicity. RESULTS: OGM detected four candidate SVs, and RNA-seq confirmed the pathogenicity of three SVs in the patient cohort. This combined approach solved three cases-two cases with de novo SVs in genes associated with autosomal dominant NDDs, including a deletion encompassing the promoter and 5'UTR of MBD5 and an intragenic duplication of PAFAH1B1, and a third case possessing an intragenic duplication in trans with a pathogenic single-nucleotide variant of PLA2G6, associated with autosomal recessive NDDs. The expression alteration of the affected genes and the tandem positioning of two intragenic duplications were confirmed by RNA-seq. In the fourth case, OGM detected a complex rearrangement involving chromosomes 2 and 6, much more complex than the de novo t(2:6)(q13;q15) indicated by conventional cytogenetic analysis. Reconstruction showed that 17 segments of 6q15 spanning 9.3 Mb were disarranged and joined 2q11.2, with four breakpoints detected in the 5' and 3' non-coding region of the NDD-associated gene SYNCRIP. RNA-seq revealed largely preserved SYNCRIP expression, leaving the pathogenicity of this complex rearrangement event uncertain. CONCLUSIONS: SVs in ES-negative NDDs can be identified by OGM, which is particularly useful for SVs in non-coding regions not covered by ES. OGM helps to construct complex SVs and provides information on the location and orientation of duplications, which is crucial for pathogenicity interpretation. The integration of RNA-seq facilitates the interpretation of the functional consequences of SVs at the transcriptional level. These findings demonstrate the utility and feasibility of combining OGM and RNA-seq in ES-negative cases with NDDs.

Single-nucleus RNA sequencing reveals cell types, genes, and regulatory factors influencing melanogenesis in the breast muscle of Xuefeng black-bone chicken.

The black-bone chicken, known for its high melanin content, holds significant economic value due to this unique trait. Particularly notable is the prominent melanin deposition observed in its breast muscle. However, the molecular mechanisms governing melanin synthesis and deposition in the breast muscle of black-bone chickens remain largely unknown. This study employed a single-nucleus transcriptome assay to identify genes associated with melanin deposition in the breast muscle of black-bone chickens, which are presumed to influence pigmentation levels. A comprehensive analysis of the nuclear transcriptome was conducted on the breast muscle of Xuefeng black-bone chickens, encompassing 18 distinct cell types, including melanocytes. Our findings revealed that STIMATE, LRRC7, ENSGALG00000049990, and GLDC play pivotal regulatory roles in melanin deposition within the breast muscle. Further exploration into the molecular mechanisms unveiled transcription factors and protein interactions suggesting that RARB, KLF15, and PRDM4 may be crucial regulators of melanin accumulation in the breast muscle. Additionally, HPGDS, GSTO1, and CYP1B1 may modulate melanin production and deposition in the breast muscle by influencing melanocyte metabolism. Our findings also suggest that melanocyte function in the breast muscle may be intertwined with intercellular signaling pathways such as PTPRK-WNT5A, NOTCH1-JAG1, IGF1R-IGF1, IDE-GCG, and ROR2-WNT5A. Leveraging advanced snRNA-seq technology, we generated a comprehensive single-cell nuclear transcriptome atlas of the breast muscle of Xuefeng black-bone chickens. This facilitated the identification of candidate genes, regulatory factors, and cellular signals potentially influencing melanin deposition and melanocyte function. Overall, our study provides crucial insights into the molecular basis of melanin deposition in chicken breast muscle, laying the groundwork for future breeding programs aimed at enhancing black-bone chicken cultivation.

Comparison of LVIS and Enterprise stent-assisted coiling embolization for ruptured intracranial aneurysms: a propensity score-matched cohort study.

The role of a low-profile visualized intraluminal support stent (LVIS) and Enterprise in the treatment of unruptured intracranial aneurysms is well established. Although previous studies have investigated one single type of stent for the treatment of ruptured intracranial aneurysms (RIA), the safety and efficacy between the two types of stents has not been fully explored. Herein we conducted a study to compare the outcomes of the two stents for treatment of RIA. This is a prospective registry database of aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to a single institution between 2018 and 2021. We collected patient baseline information, secondary complications, follow-up angiographic data, long-term prognostic outcomes, and conducted propensity score matching (PSM) analysis with 1:1 ratio and a multivariable logistic regression to compare the outcomes of the two types of stents. A total of 231 patients with RIAs were included in this study, with 108 treated using the LVIS device and 123 treated using the Enterprise device. Before PSM analysis, only the incidence of poor prognosis after 12 months was higher in the Enterprise group comparing to the LVIS group (20% vs. 10%, P = 0.049). After PSM analysis, there was a higher occurrence of delayed cerebral ischemia (DCI) in the Enterprise group compared to the LVIS group (odds ratio [OR] 3.95, 95% confidence interval [CI] [1.20-13.01], P = 0.024). However, no significant difference in prognosis was observed after PSM adjustment. Furthermore, subgroup analysis revealed that patients with female (P = 0.019), hypertension (P = 0.048), and anterior circulation aneurysms (P = 0.019) receiving the Enterprise device had a higher risk of DCI. The overall efficacy of LVIS and Enterprise in the treatment of RIA is comparable, while the incidence of DCI in the LVIS group is lower than that in the Enterprise group after PSM analysis. Registration number: NCT05738083 ( https://clinicaltrials.gov/ ).

Multiomics analysis reveal the impact of 17α-Ethinylestradiol on mortality in juvenile zebrafish.

17α-Ethinylestradiol (EE2) is known for its endocrine-disrupting effects on embryonic and adult fish. However, its impact on juvenile zebrafish has not been well established. In this study, juvenile zebrafish were exposed to EE2 at concentrations of 5 ng/L (low dose, L), 10 ng/L (medium dose, M), and 50 ng/L (high dose, H) from 21 days post-fertilization (dpf) to 49 dpf. We assessed their growth, development, behavior, transcriptome, and metabolome. The findings showed that the survival rate in the EE2-H group was 66.8 %, with all surviving fish displaying stunted growth and swollen, transparent abdomens by 49 dpf. Moreover, severe organ deformities were observed in the gills, kidneys, intestines, and heart of fish in both the EE2-H and EE2-M groups. Co-expression analysis of mRNA and lncRNA revealed that EE2 downregulated the transcription of key genes involved in the cell cycle, DNA replication, and Fanconi anemia signaling pathways. Additionally, metabolomic analysis indicated that EE2 influenced metabolism and development-related signaling pathways. These pathways were also significantly identified based on the genes regulated by lncRNA. Consequently, EE2 induced organ deformities and mortality in juvenile zebrafish by disrupting signaling pathways associated with development and metabolism. The results of this study offer new mechanistic insights into the adverse effects of EE2 on juvenile zebrafish based on multiomics analysis. The juvenile zebrafish are highly sensitive to EE2 exposure, which is not limited to adult and embryonic stages. It is a potential model for studying developmental toxicity.

A p21 Reporter iPSC Line for Evaluating CRISPR-Cas9 and Vector-Induced Stress Responses.

CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors (IDLVs) induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors.

Discovery of 2-Aryl-4-aminoquinazolin-Based LSD1 Inhibitors to Activate Immune Response in Gastric Cancer.

LSD1 (histone lysine-specific demethylase 1) has been gradually disclosed to act as an immunomodulator to enhance antitumor immune response. Despite the identification of numerous potent LSD1 inhibitors, there remains a lack of LSD1 inhibitors approved for marketing. Novel LSD1 inhibitors with different mechanisms are therefore needed. Herein, we reported a series of novel quinazoline-based LSD1 inhibitors. Among them, compound Z-1 exhibited the best LSD1 inhibitory activity (IC50 = 0.108 µM). Z-1 also acted as a selective and cellular active as an LSD1 inhibitor. Furthermore, Z-1 promoted response of gastric cancer cells to T-cell killing effect by decreasing PD-L1 expression and further attenuated the PD-1/PD-L1 interaction. In vivo, Z-1 exhibited significant suppression effect on the growth of gastric cancer cells without obvious toxicity. Therefore, Z-1 represents a potential novel immunomodulator that targets LSD1, providing a lead compound with new function mechanism for gastric cancer treatment.

Genetically predicted hypothyroidism, thyroid hormone treatment, and the risk of cardiovascular diseases: a mendelian randomization study.

BACKGROUND: In this study, we explored the impact of hypothyroidism and thyroid hormone replacement therapy on the risk of developing cardiovascular diseases, including myocardial infarction, heart failure, and cardiac death, via Mendelian randomization analysis. METHODS: Genetic instrumental variables related to hypothyroidism, levothyroxine treatment (refer to Participants were taking the medication levothyroxine sodium) and adverse cardiovascular events were obtained from a large publicly available genome-wide association study. Two-sample Mendelian randomization analysis was performed via inverse-variance weighting as the primary method. To ensure the reliability of our findings, we performed MR‒Egger regression, Cochran's Q statistic, and leave-one-out analysis. Additionally, multivariable Mendelian randomization was employed to regulate confounding factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), diabetes, cholesterol, low-density lipoprotein (LDL), triglycerides and metformin. A mediation analysis was conducted to assess the mediating effects on the association between exposure and outcome by treating atrial fibrillation and stroke as mediator variables of levothyroxine treatment and bradycardia as mediator variables of hypothyroidism. RESULTS: Genetically predicted hypothyroidism and levothyroxine treatment were significantly associated with the risk of experiencing myocardial infarction [levothyroxine: odds ratio (OR) 3.75, 95% confidence interval (CI): 1.80-7.80; hypothyroidism: OR: 15.11, 95% CI: 2.93-77.88]. Levothyroxine treatment was also significantly related to the risk of experiencing heart failure (OR: 2.16, 95% CI: 1.21-3.88). However, no associations were detected between hypothyroidism and the risk of experiencing heart failure or between hypothyroidism or levothyroxine treatment and the risk of experiencing cardiac death. After adjusting for confounding factors, the results remained stable. Additionally, mediation analysis indicated that atrial fibrillation and stroke may serve as potential mediators in the relationships between levothyroxine treatment and the risk of experiencing heart failure or myocardial infarction. CONCLUSION: The results of our study suggest a positive association between hypothyroidism and myocardial infarction and highlight the potential effects of levothyroxine treatment, the main thyroid hormone replacement therapy approach, on increasing the risk of experiencing myocardial infarction and heart failure.

In situ formed reactive oxygen species-responsive dipyridamole prodrug hydrogel: Spatiotemporal drug delivery for chemoimmunotherapy.

In the realm of combined cancer immunotherapy, the strategic combination of therapeutics targeting both cancer cells and macrophages holds immense potential. However, the major challenges remain on how to achieve facile spatiotemporal delivery of these therapies, allowing ease of manipulation and ensuring differential drug release for enhanced synergistic therapeutic effects. In the present study, we introduced a tumor microenvironment (TME)-adapted hydrogel with the phenylboronic acid-modified dipyridamole prodrug (DIPP) as a crosslinker. This prodrug hydrogel scaffold, 3BP@DIPPGel, could be formed in situ by a simple mixture of DIPP and poly(vinyl alcohol) (PVA), and loaded with a high ratio of 3-bromopyruvic acid (3BP). The 3BP@DIPPGel enables spatiotemporal localized delivery of dipyridamole (DIP) and 3BP with distinct release kinetics that effectively reshape the immunosuppressive TME. Upon reactive oxygen species (ROS) stimulation, 3BP@DIPPGel preferentially released 3BP, inducing tumor-specific pyroptosis via the ROS/BAX/caspase-3/GSDME signaling pathway and decreasing the secretion of chemokines such as CCL8 to counteract macrophage recruitment. Subsequently, the crosslinked DIP is released, triggering the tumor-associated macrophages (TAMs) polarization towards the immunostimulatory M1 phenotype via the CCR2/JAK2/STAT3 cascade signaling pathway. This dual action from 3BP@DIPPGel leads to the restoration of tumor cell immunogenicity with high efficacy and activation of immune cells. Furthermore, the 3BP@DIPPGel-based chemoimmunotherapy upregulates the expression of sialic-acid-binding Ig-like lectin 10 and hence sensitizing tumors to anti-CD24 therapy in the tumor-bearing mice. Therefore, this strategy can have significant potential in the prevention of tumor metastases and recurrence. To the best of our understanding, this study represents a pioneering showcase of tumor pyroptosis, induced by glycolytic inhibitors, which can be effectively coordinated with DIP-mediated TAM polarization for immune activation, offering a new paradigm for differentially sustained drug delivery to foster cancer immunotherapy.

Low-Dose Mildronate-Derived Lipidoids for Efficient mRNA Vaccine Delivery with Minimal Inflammation Side Effects.

mRNA vaccines have been revolutionizing disease prevention and treatment. However, their further application is hindered by inflammatory side effects, primarily caused by delivery systems such as lipid nanoparticles (LNPs). In response to this issue, we prepared cationic lipids (mLPs) derived from mildronate, a small-molecule drug, and subsequently developed the LNP (mLNP-69) comprising a low dose of mLP. Compared with the LNP (sLNP) based on SM-102, a commercially available ionizable lipid, mLNP-69 ensures effective mRNA delivery while significantly reducing local inflammation. In preclinical prophylactic and therapeutic B16-OVA melanoma models, mLNP-69 demonstrated successful mRNA cancer vaccine delivery in vivo, effectively preventing tumor occurrence or impeding tumor progression. The results suggest that the cationic lipids derived from mildronate, which exhibit efficient delivery capabilities and minimal inflammatory side effects, hold great promise for clinical application.

Intercomparison of measured and modelled photochemical ozone production rates: Suggestion of chemistry hypothesis regarding unmeasured VOCs.

Ozone (O3) pollution is a severe environmental problem in China. The incomplete understanding of atmospheric photochemical reaction mechanisms prevents us from accurately understanding the chemistry of O3 production. Here, we used an improved dual-channel reaction chamber technique to measure net photochemical O3 production rate (P(O3)net) directly in Dongguan, a typical industrial city in China. The maximum P(O3)net was 46.3 ppbv h-1 during the observation period, which is at a relatively high level compared to previous observations under different environment worldwide. We employed an observation-based box model coupled with the state-of-the-art atmospheric chemical mechanism (MCM v3.3.1) to investigate the chemistry of O3 production. Under the base scenario, the modelling underestimates P(O3)net by ~30 %. Additionally considering HO2 uptake by ambient aerosols, inorganic deposition, and Cl chemistry only caused a small change (< 13 %) in the simulation of P(O3)net. Further analysis indicates that unmeasured reactive volatile organic compounds (VOCs), such as oxygenated VOCs and branched alkenes are potential contributors to the underestimation of P(O3)net. This study underscores the underestimation of P(O3)net in conventional atmospheric modelling setups, providing a crucial scientific foundation for further investigation aimed at promoting our understanding of photochemical O3 formation.

DNA-Origami-Based Precise Molecule Assembly and Their Biological Applications.

Inspired by efficient natural biomolecule assembly with precise control on key parameters such as distance, number, orientation, and pattern, the constructions and applications of artificial precise molecule assembly are highly important in many research areas including chemistry, biology, and medicine. DNA origami, a sophisticated DNA nanotechnology with rational design, can offer a predictable, programmable, and addressable nanoscale scaffold for the precise assembly of various kinds of molecules. Herein, we summarize recent progress, particularly in the last three years, in DNA-origami-based precise molecule assembly and their emerging biological applications. We first introduce DNA origami and the progress on DNA-origami-based precise molecule assembly, including assembly of various kinds of molecules (e.g., nucleic acids, proteins, organic molecules, nanoparticles), and precise control of important parameters (e.g., distance, number, orientation, pattern). Their biological applications in sensing, imaging, therapy, bionics, biophysics, and chemical biology are then summarized, and current challenges and opportunities are finally discussed.

Engineering a Ce Promoter into a Three-Dimensional Porous Mo2C@NC Heterostructure for Hydrogen Evolution Electrocatalysis via Weakening the Mo-H Bond Strength.

The pursuit of highly efficient electrocatalysts for the alkaline hydrogen evolution reaction (HER) is of paramount importance for water splitting. However, it is still a formidable task in Mo2C-based materials because of the agglomeration and strong Mo-H binding of Mo2C units. Herein, a novel CeOCl-CeO2/Mo2C heterostructure nesting within a three-dimensional porous nitrogen-doped carbon matrix has been designed and used for catalyzing HER via simultaneous morphology and heterointerface engineering. As expected, the optimal CeOCl-CeO2(0.2)/Mo2C@3DNC exhibits impressive HER activity, with a low overpotential of 156 mV at a current density of 10 mA cm-2 coupled with a slight Tafel slope of 62.20 mV dec-1. Introducing a Ce promoter, that is CeOCl and CeO2, would endow the interface with an internal electric field and electron redistribution between CeOCl-CeO2 and Mo2C induced by the heterogeneous work function difference. Moreover, experimental investigation and density functional calculations confirm that the CeOCl-CeO2/Mo2C heterointerface can downshift the d-band center of the active Mo center, weakening the strength of the Mo-H coupling. This proposed concept, engineering Ce-based promoters into active entities involved in the heterostructure to modulate intermediate adsorption, offers a great opportunity for the design of superior electrocatalysts for energy conversion.

Single-cell dissection of the human blood-brain barrier and glioma blood-tumor barrier.

The blood-brain barrier (BBB) serves as a crucial vascular specialization, shielding and nourishing brain neurons and glia while impeding drug delivery. Here, we conducted single-cell mRNA sequencing of human cerebrovascular cells from 13 surgically resected glioma samples and adjacent normal brain tissue. The transcriptomes of 103,230 cells were mapped, including 57,324 endothelial cells (ECs) and 27,703 mural cells (MCs). Both EC and MC transcriptomes originating from lower-grade glioma were indistinguishable from those of normal brain tissue, whereas transcriptomes from glioblastoma (GBM) displayed a range of abnormalities. Among these, we identified LOXL2-dependent collagen modification as a common GBM-dependent trait and demonstrated that inhibiting LOXL2 enhanced chemotherapy efficacy in both murine and human patient-derived xenograft (PDX) GBM models. Our comprehensive single-cell RNA sequencing-based molecular atlas of the human BBB, coupled with insights into its perturbations in GBM, holds promise for guiding future investigations into brain health, pathology, and therapeutic strategies.

Simultaneous In Vivo Imaging of Neutrophil Elastase and Oxidative Stress in Atherosclerotic Plaques Using a Unimolecular Photoacoustic Probe.

Atherosclerosis is a primary global health concern due to its high morbidity and mortality. This disease is characterized by a complex interplay of chronic inflammation, oxidative stress, and proteolytic enzymes. Traditional imaging techniques struggle to capture the dynamic biochemical processes within atherosclerotic plaques. Herein, we have developed a novel unimolecular photoacoustic probe (UMAPP) that combines specific recognition sites for neutrophil elastase (NE) and the redox pair O2•‒/GSH into a cohesive molecular platform, allowing in vivo monitoring of oxidative stress and activated neutrophils within plaques. UMAPP features a boron-dipyrromethene (BODIPY) core linked to a hydrophilic NE-cleavable tetrapeptide, and dual oxidative stress-responsive catechol moieties, enabling NE-mediated modulation of photoinduced electron transfer, affecting the photoacoustic intensity at 685 nm (PA685), while oxidation and reduction of the catechol groups by O2•‒ and GSH lead to reversible, ratiometric changes in the photoacoustic spectrum. Preliminary applications of UMAPP have successfully differentiated between atherosclerotic and healthy mice, assessed the impact of pneumonia on plaque composition, and validated the probe's efficacy in drug-treatment studies, detecting molecular changes prior to observable histopathological alterations. UMAPP's integrated molecular imaging approach holds significant promise for advancing the diagnosis and management of atherosclerosis by enabling earlier and more precise detection of vulnerable plaques.

Activation of the G protein-coupled sulfakinin receptor inhibits blood meal intake in the mosquito Aedes aegypti.

Little is known about the blood-feeding physiology of arbovirus vector Aedes aegypti although this type of mosquito is known to transmit infectious diseases dengue, Zika, yellow fever, and chikungunya. Blood feeding in the female A. aegypti mosquito is essential for egg maturation and for transmission of disease agents between human subjects. Here, we identify the A. aegypti sulfakinin receptor gene SKR from the A. aegypti genome and show that SKR is expressed at different developmental stages and in varied anatomical localizations in the adult mosquito (at three days after eclosion), with particularly high expression in the CNS. Knockingdown sulfakinin and sulfakinin receptor gene expression in the female A. aegypti results in increased blood meal intake, but microinjection in the thorax of the sulfakinin peptide 1 and 2 both inhibits dose dependently blood meal intake (and delays the time course of blood intake), which is reversible with receptor antagonist. Sulfakinin receptor expressed ectopically in mammalian cells CHO-K1 responds to sulfakinin stimulation with persistent calcium spikes, blockable with receptor antagonist. These data together suggest that activation of the Gq protein-coupled (i.e., calcium-mobilizing) sulfakinin receptor inhibits blood meal intake in female A. aegypti mosquitoes and could serve as a strategic node for the future control of A. aegypti mosquito reproduction/population and disease transmission.

Lithium Orbital Hybridization Chemistry to Stimulate Oxygen Redox with Reversible Phase Evolution in Sodium-Layered Oxide Cathodes.

Searching for high energy-density electrode materials for sodium ion batteries has revealed Na-deficient intercalation compounds with lattice oxygen redox as promising high-capacity cathodes. However, anionic redox reactions commonly encountered poor electrochemical reversibility and unfavorable structural transformations during dynamic (de)sodiation processes. To address this issue, we employed lithium orbital hybridization chemistry to create Na-O-Li configuration in a prototype P2-layered Na43/60Li1/20Mg7/60Cu1/6Mn2/3O2 (P2-NaLMCM') cathode material. That Li+ ions, having low electronegativity, reside in the transition metal slabs serves to stimulate unhybridized O 2p orbitals to facilitate the stable capacity contribution of oxygen redox at high state of charge. The prismatic-type structure evolving to an intergrowth structure of the Z phase at high charging state could be simultaneously alleviated by reducing the electrostatic repulsion of O-O layers. As a consequence, P2-NaLMCM' delivers a high specific capacity of 183.8 mAh g-1 at 0.05 C and good cycling stability with a capacity retention of 80.2% over 200 cycles within the voltage range of 2.0-4.5 V. Our findings provide new insights into both tailoring oxygen redox chemistry and stabilizing dynamic structural evolution for high-energy battery cathode materials.

Cancer-Targeting and Viscosity-Activatable Near-Infrared Fluorescent Probe for Precise Cancer Cell Imaging.

Small-molecule fluorescent probes have emerged as potential tools for cancer cell imaging-based diagnostic and therapeutic applications, but their limited selectivity and poor imaging contrast hinder their broad applications. To address these problems, we present the design and construction of a novel near-infrared (NIR) biotin-conjugated and viscosity-activatable fluorescent probe, named as QL-VB, for selective recognition and imaging of cancer cells. The designed probe exhibited a NIR emission at 680 nm, with a substantial Stokes shift of 100 nm and remarkably sensitive responses toward viscosity changes in solution. Importantly, QL-VB provided an evidently enhanced signal-to-noise ratio (SNR: 6.2) for the discrimination of cancer cells/normal cells, as compared with the control probe without biotin conjugation (SNR: 1.8). Moreover, we validated the capability of QL-VB for dynamic monitoring of stimulated viscosity changes within cancer cells and employed QL-VB for distinguishing breast cancer tissues from normal tissues in live mice with improved accuracy (SNR: 2.5) in comparison with the control probe (SNR: 1.8). All these findings indicated that the cancer-targeting and viscosity-activatable NIR fluorescent probe not only enables the mechanistic investigations of mitochondrial viscosity alterations within cancer cells but also holds the potential as a robust tool for cancer cell imaging-based applications.

Chemical Recycling of Poly(cyclohexene carbonate)s via Synergistic Catalysis.

Chemical recycling of polymers to the corresponding monomers offers a valuable solution to address the current plastics crisis for creating an ideal and circular polymer economy. Here, we present a bimetallic synergistic depolymerization of the widely studied CO2-based polycarbonates, poly(cyclohexene carbonate)s, to epoxide monomers efficiently. The bimetallic CrIII-complex-mediated highly selective depolymerization and repolymerization was achieved via the regulation of reaction temperature, thus closing the circular loop of poly(cyclohexene carbonate)s in situ. Mechanistic investigation has revealed that the formation of epoxides undergoes a direct chain-end unzipping process. A bimetallic catalysis involving a nucleophilic attack of the metal-alkoxide species toward the methine carbon atom bound with an adjacent carbonyl that is activated by the other metal center features a lower energy barrier in DFT calculations, which promotes the epoxide extrusion.

Single-particle rotational microrheology enables pathological staging of macrophage foaming and antiatherosclerotic studies.

The formation of macrophage-derived foam cells has been recognized as the pathological hallmark of atherosclerotic diseases. However, the pathological evolution dynamics and underlying regulatory mechanisms remain largely unknown. Herein, we introduce a single-particle rotational microrheology method for pathological staging of macrophage foaming and antiatherosclerotic explorations by probing the dynamic changes of lysosomal viscous feature over the pathological evolution progression. The principle of this method involves continuous monitoring of out-of-plane rotation-caused scattering brightness fluctuations of the gold nanorod (AuNR) probe-based microrheometer and subsequent determination of rotational relaxation time to analyze the viscous feature in macrophage lysosomes. With this method, we demonstrated the lysosomal viscous feature as a robust pathological reporter and uncovered three distinct pathological stages underlying the evolution dynamics, which are highly correlated with a pathological stage-dependent activation of the NLRP3 inflammasome-involved positive feedback loop. We also validated the potential of this positive feedback loop as a promising therapeutic target and revealed the time window-dependent efficacy of NLRP3 inflammasome-targeted drugs against atherosclerotic diseases. To our knowledge, the pathological staging of macrophage foaming and the pathological stage-dependent activation of the NLRP3 inflammasome-involved positive feedback mechanism have not yet been reported. These findings provide insights into in-depth understanding of evolutionary features and regulatory mechanisms of macrophage foaming, which can benefit the analysis of effective therapeutical drugs as well as the time window of drug treatment against atherosclerotic diseases in preclinical studies.