In-situ activation of biomimetic single-site bioorthogonal nanozyme for tumor-specific combination therapy.

Copper-catalyzed click chemistry offers creative strategies for activation of therapeutics without disrupting biological processes. Despite tremendous efforts, current copper catalysts face fundamental challenges in achieving high efficiency, atom economy, and tissue-specific selectivity. Herein, we develop a facile "mix-and-match synthetic strategy" to fabricate a biomimetic single-site copper-bipyridine-based cerium metal-organic framework (Cu/Ce-MOF@M) for efficient and tumor cell-specific bioorthogonal catalysis. This elegant methodology achieves isolated single-Cu-site within the MOF architecture, resulting in exceptionally high catalytic performance. Cu/Ce-MOF@M favors a 32.1-fold higher catalytic activity than the widely used MOF-supported copper nanoparticles at single-particle level, as first evidenced by single-molecule fluorescence microscopy. Furthermore, with cancer cell-membrane camouflage, Cu/Ce-MOF@M demonstrates preferential tropism for its parent cells. Simultaneously, the single-site CuII species within Cu/Ce-MOF@M are reduced by upregulated glutathione in cancerous cells to CuI for catalyzing the click reaction, enabling homotypic cancer cell-activated in situ drug synthesis. Additionally, Cu/Ce-MOF@M exhibits oxidase and peroxidase mimicking activities, further enhancing catalytic cancer therapy. This study guides the reasonable design of highly active heterogeneous transition-metal catalysts for targeted bioorthogonal reactions.

Bimetal-Biligand Frameworks for Spatiotemporal Nitric Oxide-Enhanced Sono-Immunotherapy.

Sonodynamic therapy can trigger immunogenic cell death to augment immunotherapy, benefiting from its superior spatiotemporal selectivity and non-invasiveness. However, the practical applications of sonosensitizers are hindered by their low efficacy in killing cancer cells and activating immune responses. Here, two US Food and Drug Administration-approved drug ligands (ferricyanide and nitroprusside) and two types of metals (copper/iron) are selected to construct a bimetal-biligand framework (Cu[PBA-NO]). Through elaborate regulation of multiple metal/ligand coordination, the systemically administered Cu[PBA-NO] nanoagent shows sono-catalytic and NO release ability under ultrasound irradiation, which can be used for effective sono-immunotherapy. Moreover, Cu[PBA-NO] can downregulate intracellular glutathione levels that would destroy intracellular redox homeostasis and facilitate reactive oxygen species accumulation. The released tumor-associated antigens subsequently facilitate dendritic cell maturation within the tumor-draining lymph node, effectively initiating a T cell-mediated immune response and thereby bolstering the capacity to identify and combat cancer cells. This study paves a new avenue for the efficient cancer sono-immunotherapy.

Development of a cost-effective confocal Raman microscopy with high sensitivity.

Confocal Raman microscopy is a powerful technique for identifying materials and molecular species; however, the signal from Raman scattering is extremely weak. Typically, handheld Raman instruments are cost-effective but less sensitive, while high-end scientific-grade Raman instruments are highly sensitive but extremely expensive. This limits the widespread use of Raman technique in our daily life. To bridge this gap, we explored and developed a cost-effective yet highly sensitive confocal Raman microscopy system. The key components of the system include an excitation laser based on readily available laser diode, a lens-grating-lens type spectrometer with high throughput and image quality, and a sensitive detector based on a linear charge-coupled device (CCD) that can be cooled down to -30 °C. The developed compact Raman instrument can provide high-quality Raman spectra with good spectral resolution. The 3rd order 1450 cm-1 peak of Si (111) wafer shows a signal-to-noise ratio (SNR) better than 10:1, demonstrating high sensitivity comparable to high-end scientific-grade Raman instruments. We also tested a wide range of different samples (organic molecules, minerals and polymers) to demonstrate its universal application capability.

Rationally Integrating Charge-Transfer Cocrystal and Ni(II) Organometallics for Visualized Photo/Thermochromic Sensors.

Smart materials demonstrate fascinating responses to environmental physical/chemical stimuli, including thermal, photonic, electronic, humidity, or magnetic stimuli, which have attracted intensive interest in material chemistry. However, their limited/harsh stimuli-responsive behavior or sophisticated postprocessing leads to enormous challenges for practical applications. Herein, we rationally designed and synthesized thermochromic Ni(II) organometallic [(C2H5)2NH2]2NiCl4-xBrx via a facile mechanochemical strategy, which demonstrated a reversible switch from yellow to blue color with a tunable phase-transition temperature from 75.6 to 61.7 °C. The simple electrospinning technology was applied to fabricate thermochromic Ni(II) organometallic-based nanofiber membranes for temperature monitoring. Furthermore, the organic charge-transfer cocrystal with a wide spectral absorption of 300-1950 nm and a high-efficiency photothermal conversion was combined with thermochromic Ni(II) organometallics for the desired dual-stimuli photo/thermochromism. This work supplies a new strategy for realizing multiple stimuli-responsive applications, such as thermal/light sensor displays and information storage.

Endovascular Treatment With or Without Intravenous Thrombolysis for Acute Ischemic Stroke Due to Tandem Occlusion: A Systematic Review and Meta-Analysis.

BACKGROUND: Endovascular treatment (EVT) has been demonstrated to be effective for patients with tandem occlusion. The efficacy and safety of intravenous thrombolysis before EVT in patients with tandem occlusion remain debatable. METHODS AND RESULTS: We conducted a systematic review and meta-analysis with PubMed, EMBASE, and the Cochrane Library from inception to September 2023. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2 at 90 days. The secondary outcomes included the successful recanalization rate, symptomatic intracerebral hemorrhage, and mortality at 90 days. In total, 9 studies with 1838 enrolled participants were identified. Our results showed that, compared with treatment with EVT alone, intravenous thrombolysis before EVT was associated with a greater proportion of functional independence at 90 days (odds ratio [OR], 1.39 [95% CI, 1.14-1.69]; P=0.001), a greater rate of successful recanalization (OR, 1.45 [95% CI, 1.11-1.89]; P=0.007) and decreased mortality (OR, 0.68 [95% CI, 0.50-0.93]; P=0.02). Furthermore, there was no significant difference in symptomatic intracerebral hemorrhage between the intravenous thrombolysis plus EVT group and the EVT alone group (OR, 1.16 [95% CI, 0.79-1.70]; P=0.45). CONCLUSIONS: In patients with acute ischemic stroke and tandem occlusion, intravenous thrombolysis before EVT was associated with a greater rate of favorable functional outcomes and successful recanalization and a lower mortality rate without an increased risk of symptomatic intracerebral hemorrhage compared with patients receiving EVT alone.

Real-space imaging for discovering a rotated node structure in metal-organic framework.

Resolving the detailed structures of metal organic frameworks is of great significance for understanding their structure-property relation. Real-space imaging methods could exhibit superiority in revealing not only the local structure but also the bulk symmetry of these complex porous materials, compared to reciprocal-space diffraction methods, despite the technical challenges. Here we apply a low-dose imaging technique to clearly resolve the atomic structures of building units in a metal-organic framework, MIL-125. An unexpected node structure is discovered by directly imaging the rotation of Ti-O nodes, different from the unrotated structure predicted by previous X-ray diffraction. The imaged structure and symmetry can be confirmed by the structural simulations and energy calculations. Then, the distribution of node rotation from the edge to the center of a MIL-125 particle is revealed by the image analysis of Ti-O rotation. The related defects and surface terminations in MIL-125 are also investigated in the real-space images. These results not only unraveled the node symmetry in MIL-125 with atomic resolution but also inspired further studies on discovering more unpredicted structural changes in other porous materials by real-space imaging methods.

[Behavioral treatment of functional anejaculation and factors influencing the therapeutic effect].

OBJECTIVE: To study the effect of a modified behavioral treatment (MBT) on functional anejaculation and analyze the factors influencing the therapeutic efficacy. METHODS: We enrolled in this study 59 men aged 24－45 years visiting the Andrology Clinic of Shanghai First Maternity and Infant Hospital from August 2019 to May 2021 and complaining of aejaculation in sexual intercourse but normally ejaculating during masturbation. Thirty-nine of the patients underwent conventional behavioral treatment (the CBT group) and the other 20 received MBT, namely, changing the masturbation method combined with audiovisual stimulation during sexual intercourse (the MBT group). We compared the therapeutic effects between the two groups of patients, and analyzed the correlation of the outcomes of MBT with age, abstinence duration, use of audiovisual stimulation, change of the sexual position, mean bilateral testis volume and sex hormone levels. RESULTS: After treatment, 22 (37.29%) of the patients achieved successful ejaculation at least once in sexual intercourse, 11 (55.00%) in the MBT group, and the other 11 (28.21) in the CBT group, with a significantly higher effectiveness rate in the former than in the latter (P<0.05). The effectiveness rate was significantly correlated to the method of standing-position masturbation plus sexual intercourse and reduction in the frequency of masturbation among various strategies of behavioral treatment (P<0.05). CONCLUSION: MBT has a certain effect on functional anejaculation, and targeting the previous events of the patient is the key to the therapeutic efficacy. Further exploration of more effective strategies of behavioral treatment will become the trend of development in the management of functional anejaculation.

Polyoxometalates: metallodrug agents for combating amyloid aggregation.

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects ∼50 million people globally. The accumulation of amyloid-ß (Aß) plaques, a predominant pathological feature of AD, plays a crucial role in AD pathogenesis. In this respect, Aß has been regarded as a highly promising therapeutic target for AD treatment. Polyoxometalates (POMs) are a novel class of metallodrugs being developed as modulators of Aß aggregation, owing to their negative charge, polarity, and three-dimensional structure. Unlike traditional discrete inorganic complexes, POMs contain tens to hundreds of metal atoms, showcasing remarkable tunability and diversity in nuclearities, sizes, and shapes. The easily adjustable and structurally variable nature of POMs allows for their favorable interactions with Aß. This mini-review presents a balanced overview of recent progress in using POMs to mitigate amyloidosis. Clear correlations between anti-amyloid activities and structural features of POMs are also elaborated in detail. Finally, we discuss the current challenges and future prospects of POMs in combating AD.

MIKC type MADS-box transcription factor LcSVP2 is involved in dormancy regulation of the terminal buds in evergreen perennial litchi (Litchi chinensis Sonn.).

SHORT VEGETATIVE PHASE (SVP), a member of the MADS-box transcription factor family, has been reported to regulate bud dormancy in deciduous perennial plants. Previously, three LcSVPs (LcSVP1, LcSVP2 and LcSVP3) were identified from litchi genome, and LcSVP2 was highly expressed in the terminal buds of litchi during growth cessation or dormancy stages and down-regulated during growth stages. In this study, the role of LcSVP2 in governing litchi bud dormancy was examined. LcSVP2 was highly expressed in the shoots, especially in the terminal buds at growth cessation stage, whereas low expression was showed in roots, female flowers and seeds. LcSVP2 was found to be located in the nucleus and have transcription inhibitory activity. Overexpression of LcSVP2 in Arabidopsis thaliana resulted in a later flowering phenotype compared to the wild-type control. Silencing LcSVP2 in growing litchi terminal buds delayed re-entry of dormancy, resulting in significantly lower dormancy rate. The treatment also significantly up-regulated litchi FLOWERING LOCUS T2 (LcFT2). Further study indicates that LcSVP2 interacts with an AP2-type transcription factor, SMALL ORGAN SIZE1 (LcSMOS1). Silencing LcSMOS1 promoted budbreak and delayed bud dormancy. Abscisic acid (200 mg/L), which enforced bud dormancy, induced a short-term increase in the expression of LcSVP2 and LcSMOS1. Our study reveals that LcSVP2 may play a crucial role, likely together with LcSMOS1, in dormancy onset of the terminal bud and may also serve as a flowering repressor in evergreen perennial litchi.

Interleukin-11 Is Involved in Hyperoxia-induced Bronchopulmonary Dysplasia in Newborn Mice by Mediating Epithelium-Fibroblast Cross-talk.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disorder predominantly affecting preterm infants. Oxygen therapy, a common treatment for BPD, often leads to hyperoxia-induced pulmonary damage, particularly targeting alveolar epithelial cells (AECs). Crucially, disrupted lung epithelium-fibroblast interactions significantly contribute to BPD's pathogenesis. Previous studies on interleukin-11 (IL-11) in lung diseases have yielded conflicting results. Recent research, however, highlights IL-11 as a key regulator of fibrosis, stromal inflammation, and epithelial dysfunction. Despite this, the specific role of IL-11 in BPD remains underexplored. Our transcriptome analysis of normal and hyperoxia-exposed murine lung tissues revealed an increased expression of IL-11 RNA. This study aimed to investigate IL-11's role in modulating the disrupted interactions between AECs and fibroblasts in BPD. METHODS: BPD was modeled in vivo by exposing C57BL/6J neonatal mice to hyperoxia. Histopathological changes in lung tissue were evaluated with hematoxylin-eosin staining, while lung fibrosis was assessed using Masson staining and immunohistochemistry (IHC). To investigate IL-11's role in pulmonary injury contributing to BPD, IL-11 levels were reduced through intraperitoneal administration of IL-11RαFc in hyperoxia-exposed mice. Additionally, MLE-12 cells subjected to 95% oxygen were collected and co-cultured with mouse pulmonary fibroblasts (MPFs) to measure α-SMA and Collagen I expression levels. IL-11 levels in the supernatants were quantified using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Both IHC and Masson staining revealed that inhibiting IL-11 expression alleviated pulmonary fibrosis in neonatal mice induced by hyperoxia, along with reducing the expression of fibrosis markers α-SMA and collagen I in lung tissue. In vitro analysis showed a significant increase in IL-11 levels in the supernatant of MLE-12 cells treated with hyperoxia. Silencing IL-11 expression in MLE-12 cells reduced α-SMA and collagen I concentrations in MPFs co-cultured with the supernatant of hyperoxia-treated MLE-12 cells. Additionally, ERK inhibitors decreased α-SMA and collagen I levels in MPFs co-cultured with the supernatant of hyperoxia-treated MLE-12 cells. Clinical studies found increased IL-11 levels in tracheal aspirates (TA) of infants with BPD. CONCLUSION: This research reveals that hyperoxia induces IL-11 secretion in lung epithelium. Additionally, IL-11 derived from lung epithelium emerged as a crucial mediator in myofibroblast differentiation via the ERK signaling pathway, highlighting its potential therapeutic value in BPD treatment.

Deficiency of Secreted Phosphoprotein 1 Alleviates Hyperoxia-induced Bronchopulmonary Dysplasia in Neonatal Mice.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disorder characterized by impaired proximal airway and bronchoalveolar development in premature births. Secreted phosphoprotein 1 (SPP1) is involved in lung development and lung injury events, while its role was not explored in BPD. For establishing the in vivo models of BPD, a mouse model of hyperoxia-induced lung injury was generated by exposing neonatal mice to hyperoxia for 7 days after birth. Alveolar myofibroblasts (AMYFs) were treated with hyperoxia to establish the in vitro models of BPD. Based on the scRNA-seq analysis of lungs of mice housed under normoxia or hyperoxia conditions, mouse macrophages and fibroblasts were main different cell clusters between the two groups, and differentially expressed genes in fibroblasts were screened. Further GO and KEGG enrichment analysis revealed that these differentially expressed genes were mainly enriched in the pathways related to cell proliferation, apoptosis as well as the PI3K-AKT and ERK/MAPK pathways. SPP1 was found up-regulated in the lung tissues of hyperoxia mice. We also demonstrated the up-regulation of SPP1 in the BPD patients, the mouse model of hyperoxia-induced lung injury, and hyperoxia-induced cells. SPP1 deficiency was revealed to reduce the hyperoxia-induced apoptosis, oxidative stress and inflammation and increase the viability of AMYFs. In the mouse model of hyperoxia induced lung injury, SPP1 deficiency was demonstrated to reverse the hyperoxia-induced alveolar growth disruption, oxidative stress and inflammation. Overall, SPP1 exacerbates BPD progression in vitro and in vivo by regulating oxidative stress and inflammatory response via the PI3K-AKT and ERK/MAPK pathways, which might provide novel therapeutic target for BPD therapy.

Development and validation of a novel nomogram model predicting the unfavorable outcome based on NAR and collaterals status for patients with AIS.

INTRODUCTION: Stroke is a leading cause of disability and mortality globally. This study aimed to develop a prognostic nomogram based on neutrophil-to-albumin ratio (NAR) and collateral status in acute ischemic stroke (AIS) patients with anterior large vessel occlusion (LVO). MATERIAL & METHOD: 590 AIS patients with LVO assessed for regional leptomeningeal collateral (rLMC) were retrospectively enrolled, and randomly divided into a training set (n = 414) and a testing set (n = 176). Unfavorable functional outcome was defined as a modified Rankin scale (mRS) score of 3 to 6 at 3 months. We assessed the accuracy and clinical utility of the nomogram using calibration plots, area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS: Both NAR and rLMC were independently associated with unfavorable outcome at 3 months (OR=8.96, p=0.0341; OR=0.89, p=0.0002, respectively). The developed nomogram (akaike information criterion (AIC)=398.77), which included NAR, rLMC and other factors, showed good performance (the AUC for the development and validation cohorts was 0.848 and 0.840 respectively) and improved the predictive value compared to a model without NAR and rLMC, according to an overall NRI of 3.27% (p=0.2401), overall IDI of 3.27% (p=0.2414), and a higher AUC (0.848 vs 0.831). CONCLUSIONS: NAR can serve as an independent predictor in AIS patients with anterior LVO, and the nomogram incorporating NAR and rLMC is reliable in predicting unfavorable outcome. Further studies with larger sample sizes are needed to validate and extend these findings.

The gut microbial composition in polycystic ovary syndrome with hyperandrogenemia and its association with steroid hormones.

Background: Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory dysfunction, and polycystic ovaries. The mechanisms underlying ovulatory and metabolic disorders in PCOS remain elusive, hampering therapeutic development. Enhanced metabolic health correlates with increased microbiota gene content and microbial diversity. We aimed to explore the impact of gut microbiota and serum steroids on PCOS regulation associated with androgen excess. Methods: The fecal samples of patients with hyperandrogenic PCOS (n = 14) and control group with PCOS (n = 14) were analyzed by 16S rRNA gene sequencing. The peripheral venous blood of all subjects was collected to detect serum hormones. The association between gut microbiota and serum hormones was analyzed with the R language. Results: Our findings reveal that the hyperandrogenic PCOS group exhibits lower richness and diversity of gut microbiota compared to the control group. Characteristic genera in PCOS patients with hyperandrogenism include Bifidobacterium, Enterobacteriaceae_unclassified, Streptococcus, Saccharimonadaceae, Enterococcus, and Eubacterium_nodatum_group. Five hormones, including 5ß-androsterone, deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, and cortexolone, emerge as potential serum biomarkers for identifying patients with hyperandrogenic-PCOS (HA-PCOS). Furthermore, a lower vitamin D3 level may act as a susceptibility factor, suggesting that vitamin D3 supplementation could serve as a potential intervention for PCOS with hyperandrogenism. Conclusion: Specific fecal microbiota and serum steroids may be used as characteristic markers for clinical diagnosis of hyperandrogenic-PCOS. This research enhances our understanding of the intricate interplay among hormones, gut microbiota, and hyperandrogenemia in patients with PCOS.

Neutrophil-to-albumin Ratio as a Prognostic Factor in Patients with Acute Ischemic Stroke.

BACKGROUND: Neutrophil-To-Albumin Ratio (NAR) is a novel inflammatory biomarker. However, the potential prognostic value of NAR in acute ischemic stroke (AIS) remains unclear. This study aimed to evaluate whether NAR levels correlated with the 3-month modified Rankin scale (mRS) in patients with AIS. METHODS: AIS patients were included in this retrospective study. NAR was calculated as the ratio of absolute neutrophil count to serum albumin level. Logistic regression analyses were used to investigate the effect of NAR on 3-month mRS of AIS. The predictive values of NAR, albumin level, and neutrophil count were compared utilizing receiver operating characteristic (ROC) curves. Moreover, subgroup analyses and interaction tests were conducted to evaluate the consistency of NAR's effect on AIS prognosis. RESULTS: Of the 780 patients included, 403 (51.67%) had a poor clinical outcome (mRS 3-6) at 3 months. NAR was independently correlated to 3-month poor functional outcome after adjusting for confounders (Odds ratios (OR), 9.34; 95% confidence intervals (CI), 1.09 to 80.13; p =0.0417). Subgroup analysis showed a relative effect consistent with the overall population results, and no statistical interactions were found in the subgroups (all p for interaction > 0.05). The ROC curve showed that the prognosis-related cutoff value for NAR was 0.123, with corresponding specificity and sensitivity of 53.55% and 63.94%, respectively. When comparing the predictive power, NAR (0.590; 95%CI 0.549-0.630) exhibited the highest area under the curve (AUC) of ROC compared to neutrophils (0.584; 95%CI 0.543-0.624) and albumin (0.540; 95%CI 0.500-0.581). CONCLUSION: There is a positive relationship between NAR levels and 3-month poor functional outcomes in AIS patients, supporting the potential of NAR as a readily available and economic serum biomarker for the early identification of AIS prognosis. Further studies are required to validate the prognostic value and clinical utility of the NAR.

Phosphine-Catalyzed Domino Annulation of γ-Vinyl Allenoates: Synthesis of Tetrahydrofuro[3,2-c]quinoline Derivatives.

A novel phosphine-catalyzed domino annulation reaction of γ-vinyl allenoates and o-aminotrifluoacetophenones for the construction of terahydrofuro[3,2-c]quinoline derivatives has been developed. In this domino reaction, two kinds of terahydrofuro[3,2-c]quinoline compounds containing CF3 groups were obtained with good yields under mild conditions, three new C-N, C-C, and C-O bonds can be built in one step, and the reaction selectivity is achieved by adjusting the reaction conditions. Furthermore, preliminary studies on an asymmetric variant of this reaction proceeded with moderate enantioselectivity.

Outcomes and risk factors for infection after endovascular treatment in patients with acute ischemic stroke.

AIMS: Infection is a common complication following acute ischemic stroke (AIS) and significantly contributes to poor functional outcomes after stroke. This study aimed to investigate the effects of infection after endovascular treatment (post-EVT infection) on clinical outcomes and risk factors in patients with AIS. METHODS: We retrospectively analyzed AIS patients treated with endovascular treatment (EVT) between January 2016 and December 2022. A post-EVT infection was defined as any infection diagnosed within 7 days after EVT. The primary outcome was functional independence, defined as a modified Rankin scale (mRS) score of 0-2 at 90 days. A multivariable logistic regression analysis was conducted to determine independent predictors of post-EVT infection and the associations between post-EVT infection and clinical outcomes. RESULTS: A total of 675 patients were included in the analysis; 306 (45.3%) of them had post-EVT infections. Patients with post-EVT infection had a lower rate of functional independence than patients without infection (31% vs 65%, p = 0.006). In addition, patients with post-EVT infection achieved less early neurological improvement (ENI) after EVT (25.8% vs 47.4%, p < 0.001). For safety outcomes, the infection group had a higher incidence of any intracranial hemorrhage (23.9% vs 15.7%, p = 0.01) and symptomatic intracranial hemorrhage (10.1% vs 5.1%, p = 0.01). Unsuccessful recanalization (aOR 1.87, 95% CI 1.11-3.13; p = 0.02) and general anesthesia (aOR 2.22, 95% CI 1.25-3.95; p = 0.01) were identified as independent predictors for post-EVT infection in logistic regression analysis. CONCLUSION: AIS patients who develop post-EVT infections are more likely to experience poor clinical outcomes. Unsuccessful recanalization and general anesthesia were independent risk factors for the development of post-EVT infection.

Activable Nano-Immunomodulator Assembled from π-Extended Naphthalenediimide for Precision Photothermal Immunotherapy.

A nano-immunomodulator (R-NPT NP) comprising a tumor microenvironment (TME) activable resiquimod (R848) and a π-extended NIR-absorbing naphthophenanthrolinetetraone (NPT) has been engineered for spatiotemporal controlled photothermal immunotherapy. R-NPT NP demonstrated excellent photostability, while R848 promoted synergistic immunity as a toll-like receptor 7/8 (TLR7/8) agonist. Upon accumulation at the tumor site, R-NPT NP released R848 in response to redox metabolite glutathione (GSH), triggering dendritic cell (DC) activation. The photothermal effect endowed by R-NPT NP can ablate tumors directly and trigger immunogenic cell death to augment immunity after photoirradiation. The synergistic effect of GSH-liable TLR7/8 agonist and released immunogenic factors leads to a robust evocation of systematic immunity through promoted DC maturation and T cell infiltration. Thus, R-NPT NP with photoirradiation achieved 99.3 % and 98.2 % growth inhibition against primary and distal tumors, respectively.

Atomic Imaging of Multi-Dimensional Ruddlesden-Popper Interfaces in Lead-Halide Perovskites.

Ruddlesden-Popper (RP) interface with defined stacking structure will fundamentally influence the optoelectronic performances of lead-halide perovskite (LHP) materials and devices. However, it remains challenging to observe the atomic local structures in LHPs, especially for multi-dimensional RP interface hidden inside the nanocrystal. In this work, the advantages of two imaging modes in scanning transmission electron microscopy (STEM), including high-angle annular dark field (HAADF) and integrated differential phase contrast (iDPC) STEM, are successfully combined to study the bulk and local structures of inorganic and organic/inorganic hybrid LHP nanocrystals. Then, the multi-dimensional RP interfaces in these LHPs are atomically resolved with clear gap and blurred transition region, respectively. In particular, the complex interface by the RP stacking in 3D directions can be analyzed in 2D projected image. Finally, the phase transition, ion missing, and electronic structures related to this interface are investigated. These results provide real-space evidence for observing and analyzing atomic multi-dimensional RP interfaces, which may help to better understand the structure-property relation of LHPs, especially their complex local structures.

Unraveling the Molecular Size Effect on Surface Engineering of Perovskite Solar Cells.

Surface engineering in perovskite solar cells, especially for the upper surface of perovskite, is widely studied. However, most of these studies have primarily focused on the interaction between additive functional groups and perovskite point defects, neglecting the influence of other parts of additive molecules. Herein, additives with -NH3 + functional group are introduced at the perovskite surface to suppress surface defects. The chain lengths of these additives vary to conduct a detailed investigation into the impact of molecular size. The results indicate that the propane-1,3-diamine dihydroiodide (PDAI2 ), which possesses the most suitable size, exhibited obvious optimization effects. Whereas the molecules, methylenediamine dihydroiodide (MDAI2 ) and pentane-1,5-diamine dihydroiodide (PentDAI2 ) with unsuitable size, lead to a deterioration in device performance. The PDAI2 -treated devices achieved a certified power conversion efficiency (PCE) of 25.81% and the unencapsulated devices retained over 80% of their initial PCE after 600 h AM1.5 illumination.

Implication of m6A Methylation Regulators in the Immune Microenvironment of Bronchopulmonary Dysplasia.

N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of bronchopulmonary dysplasia (BPD) remains poorly characterized. Thus, the purpose of this investigation was to evaluate the effects of m6A RNA methylation regulators on the development of BPD. BPD-related transcriptome data were downloaded from the GEO database. Differentially expressed m6A methylation regulators between BPD and control group were identified. Consensus clustering was conducted for the classification of BPD and association between clusters and BPD phenotypes were explored. Analysis of differentially expressed genes (DEGs) and immune-related DEGs was performed. The GSEA, GO and KEGG analyses were used to interpret the functional enrichments. The composition of immune cell subtypes in BPD subsets was predicted by CIBERSORT analysis. Compared with the control group, expression of most m6A regulators showed significant alteration, especially for IGF2BP1/2/3. BPD was classified into 2 subsets, and cluster 1 was correlated with severe BPD. Furthermore, the results of functional enrichment analyses showed a disturbed immune-related signaling pathway. Based on CIBERSORT analysis, we found that the proportion of immune cell subsets changed between cluster 1 and cluster 2. Our study revealed the implication of m6A methylation regulators in the development of BPD, which might provide a novel insight for the diagnosis and treatment of BPD.