Functional dissection of complex and molecular trait variants at single nucleotide resolution.

Identifying the causal variants and mechanisms that drive complex traits and diseases remains a core problem in human genetics. The majority of these variants have individually weak effects and lie in non-coding gene-regulatory elements where we lack a complete understanding of how single nucleotide alterations modulate transcriptional processes to affect human phenotypes. To address this, we measured the activity of 221,412 trait-associated variants that had been statistically fine-mapped using a Massively Parallel Reporter Assay (MPRA) in 5 diverse cell-types. We show that MPRA is able to discriminate between likely causal variants and controls, identifying 12,025 regulatory variants with high precision. Although the effects of these variants largely agree with orthogonal measures of function, only 69% can plausibly be explained by the disruption of a known transcription factor (TF) binding motif. We dissect the mechanisms of 136 variants using saturation mutagenesis and assign impacted TFs for 91% of variants without a clear canonical mechanism. Finally, we provide evidence that epistasis is prevalent for variants in close proximity and identify multiple functional variants on the same haplotype at a small, but important, subset of trait-associated loci. Overall, our study provides a systematic functional characterization of likely causal common variants underlying complex and molecular human traits, enabling new insights into the regulatory grammar underlying disease risk.

Improving Three-Photon Fluorescence of Near-Infrared Quantum Dots for Deep Brain Imaging by Suppressing Biexciton Decay.

Three-photon fluorescence microscopy (3PFM) is a promising brain research tool with submicrometer spatial resolution and high imaging depth. However, only limited materials have been developed for 3PFM owing to the rigorous requirement of the three-photon fluorescence (3PF) process. Herein, under the guidance of a band gap engineering strategy, CdTe/CdSe/ZnS quantum dots (QDs) emitting in the near-infrared window are designed for constructing 3PF probes. The formation of type II structure significantly increased the three-photon absorption cross section of QDs and caused the delocalization of electron-hole wave functions. The time-resolved transient absorption spectroscopy confirmed that the decay of biexcitons was significantly suppressed due to the appropriate band gap alignment, which further enhanced the 3PF efficiency of QDs. By utilizing QD-based 3PF probes, high-resolution 3PFM imaging of cerebral vasculature was realized excited by a 1600 nm femtosecond laser, indicating the possibility of deep brain imaging with these 3PF probes.

Biosynthesis of CuTe Nanorods with Large Molar Extinction Coefficients for NIR-II Photoacoustic Imaging.

Photoacoustic imaging (PAI) in the second near-infrared region (NIR-II), due to deeper tissue penetration and a lower background interference, has attracted widespread concern. However, the development of NIR-II nanoprobes with a large molar extinction coefficient and a high photothermal conversion efficiency (PCE) for PAI and photothermal therapy (PTT) is still a big challenge. In this work, the NIR-II CuTe nanorods (NRs) with large molar extinction coefficients ((1.31 ± 0.01) × 108 cm-1·M-1 at 808 nm, (7.00 ± 0.38) × 107 cm-1·M-1 at 1064 nm) and high PCEs (70% at 808 nm, 48% at 1064 nm) were synthesized by living Staphylococcus aureus (S. aureus) cells as biosynthesis factories. Due to the strong light-absorbing and high photothermal conversion ability, the in vitro PA signals of CuTe NRs were about 6 times that of indocyanine green (ICG) in both NIR-I and NIR-II. In addition, CuTe NRs could effectively inhibit tumor growth through PTT. This work provides a new strategy for developing NIR-II probes with large molar extinction coefficients and high PCEs for NIR-II PAI and PTT.

Correlation analysis and clinical significance of changes in upper thoracic vertebra tilt and clavicle angle pre- and post-operation.

The imbalance of the lateral shoulder is reflected by the clavicle angle (CA) in radiology. It remains unclear how to achieve postoperative lateral shoulder balance (LSB) after spinal deformity correction surgery. A retrospective analysis was conducted on AIS patients who underwent surgery by the same spine surgeon at our hospital from 2016 to 2020. A total of 110 patients with spinal deformity were included in the study to verify the correlation between the T1-T5 tilt angle and CA before and after surgery, as well as the relation-ship between the change in T1-T5 tilt angle before and after surgery and the change in CA before and after surgery. By comparing the correlation coefficients, it was found that there may not be a direct relationship between the pre- and postoperative tilt angles of T1-5 and CA, but their changes were closely related to the changes in CA. The change in T1 tilt angle after orthopaedic surgery was significantly correlated with the change in CA, with a correlation coefficient of 0.976, indicating a close relationship between T1 and the clavicle. As the vertebrae moved down, the correlation gradually decreased. In summary, this study suggests that there is a close relationship between T1-T5 and the clavicle and that the change in T1 tilt angle after spinal scoliosis correction surgery is significantly correlated with CA, which decreases as the vertebra moves down.

Biosynthesis of NIR-II Ag2 Se Quantum Dots with Bacterial Catalase for Photoacoustic Imaging and Alleviating-Hypoxia Photothermal Therapy.

Developing the second near-infrared (NIR-II) photoacoustic (PA) agent is of great interest in bioimaging. Ag2 Se quantum dots (QDs) are one kind of potential probe for applications in NIR-II photoacoustic imaging (PAI). However, the surfaces with excess anions of Ag2 Se QDs, which increase the probability of nonradiative transitions of excitons benefiting PA imaging, are not conducive to binding electron donor ligands for potential biolabeling and imaging. In this study, Staphylococcus aureus (S. aureus) cells are driven for the biosynthesis of Ag2 Se QDs with catalase (CAT). Biosynthesized Ag2 Se (bio-Ag2 Se-CAT) QDs are produced in Se-enriched environment of S. aureus and have a high Se-rich surface. The photothermal conversion efficiency of bio-Ag2 Se-CAT QDs at 808 and 1064 nm is calculated as 75.3% and 51.7%, respectively. Additionally, the PA signal responsiveness of bio-Ag2 Se-CAT QDs is ≈10 times that of the commercial PA contrast agent indocyanine green. In particular, the bacterial CAT is naturally attached to bio-Ag2 Se-CAT QDs surface, which can effectively relieve tumor hypoxia. The bio-Ag2 Se-CAT QDs can relieve heat-initiated oxidative stress while undergoing effective photothermal therapy (PTT). Such biosynthesis method of NIR-II bio-Ag2 Se-CAT QDs opens a new avenue for developing multifunctional nanomaterials, showing great promise for PAI, hypoxia alleviation, and PTT.

Improving fine-mapping by modeling infinitesimal effects.

Fine-mapping aims to identify causal genetic variants for phenotypes. Bayesian fine-mapping algorithms (for example, SuSiE, FINEMAP, ABF and COJO-ABF) are widely used, but assessing posterior probability calibration remains challenging in real data, where model misspecification probably exists, and true causal variants are unknown. We introduce replication failure rate (RFR), a metric to assess fine-mapping consistency by downsampling. SuSiE, FINEMAP and COJO-ABF show high RFR, indicating potential overconfidence in their output. Simulations reveal that nonsparse genetic architecture can lead to miscalibration, while imputation noise, nonuniform distribution of causal variants and quality control filters have minimal impact. Here we present SuSiE-inf and FINEMAP-inf, fine-mapping methods modeling infinitesimal effects alongside fewer larger causal effects. Our methods show improved calibration, RFR and functional enrichment, competitive recall and computational efficiency. Notably, using our methods' posterior effect sizes substantially increases polygenic risk score accuracy over SuSiE and FINEMAP. Our work improves causal variant identification for complex traits, a fundamental goal of human genetics.

SOD3 regulates FLT1 to affect bone metabolism by promoting osteogenesis and inhibiting adipogenesis through PI3K/AKT and MAPK pathways.

Osteoporosis is a chronic disease that seriously affects the quality of life and longevity of the elderly, so exploring the mechanism of osteoporosis is crucial for drug development and treatment. Bone marrow mesenchymal stem cells are stem cells with multiple differentiation potentials in bone marrow, and changing their differentiation direction can change bone mass. As an extracellular superoxide dismutase, Superoxide Dismutase 3 (SOD3) has been proved to play an important role in multiple organs, but the detailed mechanism of action in bone metabolism is still unclear. In this study, the results of clinical serum samples ELISA and single cell sequencing chip analysis proved that the expression of SOD3 was positively correlated with bone mass, and SOD3 was mainly expressed in osteoblasts and adipocytes and rarely expressed in osteoblasts in BMSCs. In vitro experiments showed that SOD3 can promote osteogenesis and inhibit adipogenesis. Compared with WT mice, the mice that were knocked out of SOD3 had a significant decrease in bone mineral density and significant changes in related parameters. The results of HE and IHC staining suggested that knocking out SOD3 would lead to fat accumulation in the bone marrow cavity and weakened osteogenesis. Both in vitro and in vivo experiments indicated that SOD3 affects bone metabolism by promoting osteogenesis and inhibiting adipogenesis. The results of transcriptome sequencing and revalidation showed that SOD3 can affect the expression of FLT1. Through in vitro experiments, we proved that FLT1 can also promote osteogenesis and inhibit adipogenesis. In addition, through the repeated experiments, the interaction between the two molecules (SOD3 and FLT1) was verified again. Finally, it was verified by WB that SOD3 regulates FLT1 to affect bone metabolism through PI3K/AKT and MAPK pathways.

Jointly Predicting Postprandial Hypoglycemia and Hyperglycemia Using Continuous Glucose Monitoring Data in Type 1 Diabetes.

The development of continuous glucose monitoring (CGM) systems has enabled people with type 1 diabetes mellitus (T1DM) to track their glucose trajectory in real-time and inspired research in personalised glucose prediction. In this paper, our aim is to predict postprandial abnormal-glycemia events. Different from prior research which focuses on hypoglycemia only, we make the first attempt to establish our problem as the joint prediction of hyperglycemia and hypoglycemia. On this basis, we propose a machine learning model that learns from the pattern of 1 hour past glucose and makes predictions for the two tasks simultaneously using a unified backbone. Key benefits of our methodology include 1) requiring only the CGM sequence as the input, thus making it more widely applicable than other counterparts using extra inputs such as the nutrition details, and 2) minimising the computational cost as the two tasks are unified into a single model. Our experiments on the openly available OhioT1DM dataset achieve state-of-the-art performance (Matthew's correlation coefficient of 0.61 for hyperglycemia and 0.48 for hypoglycemia). To encourage further study, we release our codes at https://github.com/r-cui/PostprandialHyperHypoPrediction under the MIT license.

Lenvatinib plus Immune Checkpoint Inhibitors versus Lenvatinib monotherapy as treatment for advanced hepatocellular carcinoma: a meta-analysis.

Lenvatinib, an FDA-approved first-line oral multi-kinase inhibitor for advanced hepatocellular carcinoma (aHCC), has demonstrated promise for treatment. Nevertheless, findings from the Leap-002 study suggest that the addition of anti-vascular drugs to Lenvatinib may not yield significant improvements in survival rate. This meta-analysis aims to comprehensively assess the effectiveness of Lenvatinib, both as a standalone treatment and in combination with immune checkpoint inhibitors (ICIs), in managing advanced aHCC patients. We retrieved relevant studies published up to March 1, 2023, from databases such as PubMed, the Cochrane Library, Web of Science, and Embase. Subsequently, we conducted an analysis using REVMAN 5.3 and Stata MP 14.0 software, following quality assessment and data extraction procedures. A random effects model was employed to calculate the risk ratio (HR) using a 95% confidence interval (CI). The initial literature search yielded 921 results. However, after multiple rounds of exclusion and the removal of unrelated studies, 26 papers met the screening criteria. After a thorough examination of the full texts, we found that 8 studies met the analysis criteria. The combination of Lenvatinib with ICIs demonstrated significant improvement in overall survival (OS) (HR=1.53, 95% CI: 1.34-1.74; P<0.001) and progression-free survival (PFS) (HR=1.51, 95% CI: 1.34-1.72; P<0.001). Furthermore, subgroup analysis, categorized by the duration of follow-up, revealed that for the 3-year combined OS (HR=2.21, 95% CI: 1.79-2.73; Z=7.40, P<0.05), the combination therapy significantly outperformed monotherapy, leading to a 2.21-fold increase in OS for patients during the 3-year follow-up period. Nevertheless, for non-3-year combinations (HR=1.206, 95% CI: 1.020-1.425; Z=2.19, P<0.05), there was merely a 1.206-fold increase in effectiveness compared to single therapy for follow-ups of both longer and shorter durations. This might be attributed to the insufficient representation of HBV-related aHCC cases and the Asian population in the study, along with the increased availability of second-line treatment options for advanced cancer, which can influence the observed effectiveness of immunotherapy.

[Analysis of Vegetation Change and Influencing Factors in Southwest Alpine Canyon Area].

The southwest alpine canyon area is a typical ecologically fragile area. Understanding the characteristics of vegetation change here and its influencing factors can provide a theoretical basis for formulating countermeasures for ecological environment construction in the southwest alpine canyon area and has practical significance for realizing the harmonious and unified development of the regional economy, environment, and ecology. Based on the data set of NDVI, socio-economic factors, and natural factors from 2000 to 2019, the spatial and temporal variation and stability characteristics of NDVI in the southwest alpine canyon area were analyzed by using the methods of unary linear regression, Hurst index, geographic detector model, and coefficient of variation, and the influencing factors of the spatial differentiation of NDVI were also discussed. The results showed that:① in terms of spatial distribution, the vegetation was high in the southeast and low in the northwest. The area covered by medium and high vegetation accounted for 71.71%, and the vegetation cover was at a relatively high level. From the perspective of time, the area of vegetation showing an improvement trend accounted for 85.90%, and the recovery effect was obvious, and the future vegetation change trend will continue to be improved. ② Elevation, vegetation type, and soil type were the main factors affecting the spatial differentiation of NDVI, and the q value was no less than 0.40. Temperature and rainfall were secondary factors, with q values of 0.274 and 0.225, respectively. The dual-factor interaction enhanced the single factor influence, which was manifested as the dual-factor enhancement and nonlinear enhancement relationship. The highest q value was 0.714 for the combination of altitude ∩ vegetation, followed by 0.688 for the combination of altitude ∩ soil. ③ The overall stability of NDVI during the study period was good, and the proportion of the regional area with low fluctuating changes and slightly low fluctuating changes was 89.95%. The area with moderate fluctuation accounted for 10.05%, concentrated in the relatively fragile ecological environment with factors such as high altitude, low temperature, little rainfall, barren soil, and sparse vegetation. Vegetation change is the result of a combination of multiple factors, so it is necessary to adapt to local conditions and adopt different strategies to restore the ecological environment of the southwest alpine canyon area.

Specific gastrointestinal microbiota profiles in Chinese Tan sheep are associated with lauric acid content in muscle.

The biological mechanisms underlying meat quality remain unclear. Currently, many studies report that the gastrointestinal microbiota is essential for animal growth and performance. However, it is uncertain which bacterial species are specifically associated with the meat quality traits. In this study, 16S rDNA and metagenomic sequencing were performed to explore the composition and function of microbes in various gastrointestinal segments of Tan sheep and Dorper sheep, as well as the relationship between microbiota and meat quality (specifically, the fatty acid content of the muscle). In the ruminal, duodenal, and colonic microbiome, several bacteria were uniquely identified in respective breeds, including Agrobacterium tumefaciens, Bacteroidales bacterium CF, and several members of the family Oscillospiraceae. The annotation of GO, KEGG, and CAZYme revealed that these different bacterial species were linked to the metabolism of glucose, lipids, and amino acids. Additionally, our findings suggested that 16 microbial species may be essential to the content of fatty acids in the muscle, especially C12:0 (lauric acid). 4 bacterial species, including Achromobacter xylosoxidans, Mageeibacillus indolicus, and Mycobacterium dioxanotrophicus, were positively correlated with C12:0, while 13 bacteria, including Methanobrevibacter millerae, Bacteroidales bacterium CF, and Bacteroides coprosuis were negatively correlated with C12:0. In a word, this study provides a basic data for better understanding the interaction between ruminant gastrointestinal microorganisms and the meat quality traits of hosts.

Expanding the role of combined immunochemotherapy and immunoradiotherapy in the management of head and neck cancer (Review).

Immunotherapy has become one of the most promising approaches in tumor therapy, and there are numerous associated clinical trials in China. As an immunosuppressive tumor, head and neck squamous cell carcinoma (HNSCC) carries a high mutation burden, making immune checkpoint inhibitors promising candidates in this field due to their unique mechanism of action. The present review outlines a comprehensive multidisciplinary cancer treatment approach and elaborates on how combining immunochemotherapy and immunoradiotherapy guidelines could enhance clinical efficacy in patients with HNSCC. Furthermore, the present review explores the immunology of HNSCC, current immunotherapeutic strategies to enhance antitumor activity, ongoing clinical trials and the future direction of the current immune landscape in HNSCC. Advanced-stage HNSCC presents with a poor prognosis, low survival rates and minimal improvement in patient survival trends over time. Understanding the potential of immunotherapy and ways to combine it with surgery, chemotherapy and radiotherapy confers good prospects for the management of human papillomavirus (HPV)-positive HNSCC, as well as other HPV-positive malignancies. Understanding the immune system and its effect on HNSCC progression and metastasis will help to uncover novel biomarkers for the selection of patients and to enhance the efficacy of treatments. Further research on why current immune checkpoint inhibitors and targeted drugs are only effective for some patients in the clinic is needed; therefore, further research is required to improve the overall survival of affected patients.

Band Gap Engineering Improves Three-Photon Luminescence of Quantum Dots for Deep Brain Imaging.

Three-photon fluorescence microscopy (3PFM) has emerged as a promising tool in monitoring the structures and functions of the brain. Compared to the various imaging technologies, 3PFM enables a deep-penetrating depth attributed to tighter excitation confinement and suppressed photon scattering. However, the shortage of three-photon probes with a large absorption cross section (σ3) substantially limits its uses. Herein, CdSe/CdS/ZnS quantum dots (QDs) with enhanced 3PF performance were synthesized via the band gap engineering strategy. The introduction of a CdS interlayer with optimized thickness between the emitting CdSe core and the ZnS shell significantly enhanced the 3P absorption cross section of QDs, which originated from the intrinsic piezoelectric polarization effect and the change of the core/shell structure from type-I to quasi-type-II. In addition, the outer ZnS layer compensated the poor electronic passivation of CdS, providing a high level of passivation for the improvement of quantum yield as well as the 3P action cross section of QDs. Under the excitation of a 1600 nm femtosecond laser, PEGylated CdSe/CdS/ZnS QDs were used for in vivo 3PFM imaging of cerebral vessels with high resolution. A tiny capillary with a diameter of 0.8 µm could be resolved at the imaging depth of 1550 µm in a mouse brain with an opened skull. A penetration depth of 850 µm beneath the skull was also achieved using a mouse model with an intact skull.

Prevalence of psoriatic arthritis in Chinese population with psoriasis: A multicenter study conducted by experienced rheumatologists.

BACKGROUND: Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis. METHODS: Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists. RESULTS: A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%). CONCLUSION: The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.

Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study.

A balanced vaginal microbiome dominated by Lactobacillus can help promote women's reproductive health, with Lactobacillus crispatus showing the most beneficial effect. However, the potential role of vaginal microbiomes in hypertensive disorders of pregnancy (HDP) development is not thoroughly explored. In this nested case-control study based on an assisted reproductive technology follow-up cohort, we prospectively assessed the association between pregestational vaginal microbiomes with HDP by collecting vaginal swabs from 75 HDP cases (HDP group) and 150 controls (NP group) and using 16S amplicon sequencing for bacterial identification. The vaginal microbial composition of the HDP group significantly differed from that of the NP group. The abundance of L. crispatus was significantly lower, and the abundances of Gardnerella vaginalis was significantly higher, in the HDP group than in the NP group. Of note, L. crispatus-dominated vaginal community state type was associated with a decreased risk for HDP (odds ratio = 0.436; 95% confidence interval, 0.229 to 0.831) compared with others. Additionally, network analysis revealed different bacterial interactions with 61 and 57 exclusive edges in the NP and HDP groups, respectively. Compared with the HDP group, the NP group showed a higher weighted degree and closeness centrality. Several taxa, including G. vaginalis, L. iners, and bacterial vaginosis-associated bacteria (Prevotella, Megasphaera, Finegoldia, and Porphyromonas), were identified as "drivers" for network rewiring. Notable alterations of predicted pathways involved in amino acid, cofactor, and vitamin metabolism; membrane transport; and bacterial toxins were observed in the HDP group. IMPORTANCE The etiology of HDP remains unclear to date. Effective methods for the individualized prediction and prevention are lacking. Pregestational vaginal dysbiosis precedes the diagnosis of HDP, providing a novel perspective on the etiology of HDP. Early pregnancy is the critical period of placental development, and abnormal placentation initiates HDP development. Thus, disease prevention should be considered before pregnancy. Vaginal microbiome characterization and probiotic interventions before pregnancy are preferred because of their safety and potential for early prevention. This study is the first to prospectively assess associations between pregestational vaginal microbiome and HDP. L. crispatus-dominated vaginal community state type is linked to a reduced risk for HDP. These findings suggest that vaginal microbiome characterization may help identify individuals at high risk for HDP and offer potential targets for the development of novel pregestational intervention methods.

Fasting produces antidepressant-like effects via activating mammalian target of rapamycin complex 1 signaling pathway in ovariectomized mice.

Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test. However, whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established. Therefore, in this study, we simulated perimenopausal depression via an ovariectomy in mice, and subjected them to a single 9-hour fasting 7 days later. We found that the ovariectomy increased the time spent immobile in the forced swimming test, inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefrontal cortex, and decreased the density of dendritic spines in the hippocampus. The 9-hour acute fasting alleviated the above-mentioned phenomena. Furthermore, all of the antidepressant-like effects of 9-hour fasting were reversed by an inhibitor of the mammalian target of rapamycin complex 1. Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting. These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus. Thus, fasting may be a potential treatment for depression.

Encapsulating Semiconductor Quantum Dots in Supramolecular Cages Enables Ultrafast Guest-Host Electron and Vibrational Energy Transfer.

In the field of supramolecular chemistry, host-guest systems have been extensively explored to encapsulate a wide range of substrates, owing to emerging functionalities in nanoconfined space that cannot be achieved in dilute solutions. However, host-guest chemistry is still limited to encapsulation of small guests. Herein, we construct a water-soluble metallo-supramolecular hexagonal prism with a large hydrophobic cavity by anchoring multiple polyethylene glycol chains onto the building blocks. Then, assembled prisms are able to encapsulate quantum dots (QDs) with diameters of less than 5.0 nm. Furthermore, we find that the supramolecular cage around each QD strongly modifies the photophysics of the QD by universally increasing the rates of QD relaxation processes via ultrafast electron and vibrational energy transfer. Taken together, these efforts expand the scope of substrates in host-guest systems and provide a new approach to tune the optical properties of QDs.

Activatable Lanthanide Nanoprobes with Dye-Sensitized Second Near-Infrared Luminescence for in Vivo Inflammation Imaging.

Lanthanide nanoparticles exhibit unique photophysical properties and thus emerge as promising second near-infrared (NIR-II) optical agents. However, the limited luminescence brightness hampers their construction of activatable NIR-II probes. Herein, we report the synthesis of dye-sensitized lanthanide nanoprobes (NaGdF4:Nd/ICG; indocyanine green (ICG)) and their further development for in vivo activatable imaging of hypochlorite (ClO-). Dye sensitization using ICG not only shifts the optimal doping concentration of Nd3+ from 5 to 20 mol % but also leads to a 5-fold NIR-II enhancement relative to the ICG-free counterpart. Mechanistic studies reveal that such a luminescence enhancement of NaGdF4:Nd at high Nd3+ concentration is ascribed to an alleviated cross-relaxation effect due to the broad absorption of ICG and faster energy transfer process. Taking advantage of dye oxidation, the nanoprobes enable activatable NIR-II imaging of hypochlorous acid (ClO-) in a drug-induced lymphatic inflammation mouse model. This work thus provides a simple, yet effective luminescence enhancement strategy for constructing lanthanide nanoprobes at higher activator doping concentration toward activatable NIR-II molecular imaging.

Near-infrared-IIb emitting single-atom catalyst for imaging-guided therapy of blood-brain barrier breakdown after traumatic brain injury.

The blood-brain barrier breakdown, as a prominent feature after traumatic brain injury, always triggers a cascade of biochemical events like inflammatory response and free radical-mediated oxidative damage, leading to neurological dysfunction. The dynamic monitoring the status of blood-brain barrier will provide potent guidance for adopting appropriate clinical intervention. Here, we engineer a near-infrared-IIb Ag2Te quantum dot-based Mn single-atom catalyst for imaging-guided therapy of blood-brain barrier breakdown of mice after traumatic brain injury. The dynamic change of blood-brain barrier, including the transient cerebral hypoperfusion and cerebrovascular damage, could be resolved with high spatiotemporal resolution (150 ms and ~ 9.6 µm). Notably, the isolated single Mn atoms on the surface of Ag2Te exhibited excellent catalytic activity for scavenging reactive oxygen species to alleviate neuroinflammation in brains. The timely injection of Mn single-atom catalyst guided by imaging significantly promoted the reconstruction of blood-brain barrier and recovery of neurological function after traumatic brain injury.