Search

Abstract Photothermal immunotherapy is regarded as the ideal cancer therapeutic modality to against malignant solid tumors; however, its therapeutic benefits are often modest and require improvement. In this study, a thermoresponsive nanoparticle (BTN@LND) composed of a photothermal agent (PTA) and pyroptosis inducer (lonidamine) were developed to enhance immunotherapy applications. Specifically, our “two-step” donor engineering strategy produced the strong NIR-II-absorbing organic small-molecule PTA (BTN) that exhibited high NIR-II photothermal performance (ε1064 = 1.51 × 104 M−1 cm−1, η = 75.8%), and this facilitates the diagnosis and treatment of deep tumor tissue. Moreover, the fabricated thermally responsive lipid nanoplatform based on BTN efficiently delivered lonidamine to the tumor site and achieved spatiotemporal release triggered by the NIR-II photothermal effect. In vitro and in vivo experiments demonstrated that the NIR-II photothermal therapy (PTT)-mediated on-demand release of cargo effectively faciliated tumor cell pyroptosis, thereby intensifying the immunogenic cell death (ICD) process to promote antitumor immunotherapy. As a result, this intelligent component bearing photothermal and chemotherapy can maximally suppress the growth of tumors, thus providing a promising approach for pyroptosis/NIR-II PTT synergistic therapy against tumors. Graphical Abstract

Abstract To investigate the sex differences in disability-adjusted life years (DALYs) due to ischemic stroke (IS) by year, location and age. We extracted sex-specific data on DALYs number, age-standardized DALYs rate (ASDR) and all-age DALYs rate of IS by year, location and age from the Global Burden of Diseases study 2019. The estimated annual percentage changes (EAPC) were calculated to evaluate the temporal trend of ASDR. For both sexes, although the ASDR of IS slightly decreased from 1990 to 2019, there has been an 60.3% increase in DALYs number worldwide. Sex difference in DALYs number (men minus women) decreased from − 2.83 million in 1990 to 0.14 million in 2019, while the men to women’s ASDR ratio slightly increased from 1.10 in 1990 to 1.21 in 2019. The sex differences in IS DALYs showed remarkable regional variation. The largest sex differences in DALYs number and ASDR were in China and Vietnam. Middle-aged men had a higher IS DALYs than their age-matched counterparts. High systolic blood pressure accounted for the highest DALYs number in 2019, but the top three attributable risk factors that had the greatest sex differences were tobacco, dietary risk, and alcohol use. Sex differences in IS DALYs varied by year, location and age, mostly attributed to the disproportion of cardiovascular risk factors between sexes. Considering the population growth and aging, it is necessary to monitor the sex difference in IS DALYs in different populations and thus provide evidence for local administration to improve current preventive and management strategies of IS.

Histomonas meleagridis is a protozoan parasite that causes histomonosis in gallinaceous birds such as turkeys and chickens. Since the banning and restricted usage of effective drugs such as nitarsone, 80–100% morbidity and mortality occur in turkeys and 20–30% mortality in chickens. New ideas are needed to resolve the re-emergence of histomonosis in poultry. In this study, the α-actinin encoding gene from H. meleagridis was cloned. The 1839-bp gene encoding 612 amnio acids showed close phylogenetic relationships with Trichomonas vaginalis and Tritrichomonas foetus. It was then inserted into the prokaryotic expression vector pET28a(+) and induced with isopropyl-β-D-thiogalactopyranoside. A 73 kDa recombinant protein rHmα-actinin 1 was obtained and purified with a Ni-NTA chromatography column. rHmα-actinin 1 was recognized by mouse anti-rHmα-actinin 1 polyclonal antibody, mouse anti-rHmα-actinin 1 monoclonal antibody, and rehabilitation sera from H. meleagridis infected chickens. Native α-actinin 1 in the total proteins of H. meleagridis can also be detected with mouse anti-rHmα-actinin monoclonal antibody. Immunolocalization assays showed that Hmα-actinin 1 was mainly distributed in the cytoplasm of virulent histomonads JSYZ-D9 and in the peripheral regions (near the plasma membrane) of attenuated histomonads JSYZ-D195. Based on in vivo experiment, when chickens were subcutaneously immunized with rHmα-actinin 1 at 5 and 12 days old and then challenged with H. meleagridis at 19 days old, rHmα-actinin 1 reduced the lesion scores 12 days after infection (31 days old) and increased the body weight gain during the challenged period (19–31 days old). Furthermore, it also strengthened the cellular and humoral immune responses 7 days after the second immunization (19 days old). In conclusion, Hmα-actinin 1 could be used as a candidate antigen to develop vaccines against chicken histomonosis.

The syntheses of two triads are reported. Each triad is composed of two perylene-monoimides linked to a porphyrin via an ethyne unit, which bridges the perylene 9-position and a porphyrin 5- or 15-position. Each triad also contains a single tether composed of an alkynoic acid or an isophthalate unit. Each triad provides panchromatic absorption (350–700 nm) with fluorescence emission in the near-infrared region (733 or 743 nm; fluorescence quantum yield ~0.2). The syntheses rely on the preparation of trans-AB-porphyrins bearing one site for tether attachment (A), an aryl group (B), and two open meso-positions. The AB-porphyrins were prepared by the condensation of a 1,9-diformyldipyrromethane and a dipyrromethane. The installation of the two perylene-monoimide groups was achieved upon the 5,15-dibromination of the porphyrin and the subsequent copper-free Sonogashira coupling, which was accomplished before or after the attachment of the tether. The syntheses provide relatively straightforward access to a panchromatic absorber for use in bioconjugation or surface-attachment processes.

Renal function estimated by various biomarkers predicting for adverse cardiovascular events has not been well-identified in received percutaneous coronary intervention (PCI) for chronic total occlusion (CTO), the advanced stages of atherosclerosis. We aim to determine whether the serum cystatin C-based-estimated glomerular filtration rate (eGFR) can have an improved predictive value in patients with CTO lesions undergoing PCI as compared with multiple creatinine-based estimates of kidney function. Six hundred and seventy-one patients received CTO PCI were retrospectively included in the study. The eGFR was calculated by modification of diet in renal disease equation for Chinese (cMDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations at baseline, respectively. Then, the cohort was categorized into three groups according to standard KDIGO kidney stages based on eGFR. The primary endpoint was all-cause mortality, and the secondary endpoint was cardiac death. Strikingly, cystatin C-based eGFR showed a better performance with the greater area being under the receiver operating characteristic (ROC) curve (0.73 for all-cause mortality and 0.73 for cardiac death, separately) and a better assessment for survival free from adverse event across renal levels among four eGFR equations. Compared with eGFR calculated by other formulas, serum cystatin C-based eGFR showed the highest prognostic value for both all-cause mortality (adjusted HR 3.6, 95% CI 1.6–8.1, P = 0.002) and cardiac death (adjusted HR 2.9, 95% CI 1.0–8.1, P = 0.028). Moreover, cystatin C-based eGFR significantly improved the risk reclassification of event with a high value of net reclassification improvement and integrated discrimination improvement. This study may prove that cystatin C-based eGFR is a better predictor of both all-cause mortality and cardiac death than other equations in populations with CTO undergoing PCI.

Streptococcus suis type 2 (SS2) is an important swine pathogen and zoonosis agent. A/J mice are significantly more susceptible than C57BL/6 (B6) mice to SS2 infection, but the genetic basis is largely unknown. Here, alterations in gene expression in SS2 (strain HA9801)-infected mice were identified using Illumina mouse BeadChips. Microarray analysis revealed 3,692 genes differentially expressed in peritoneal macrophages between A/J and B6 mice due to SS2 infection. Between SS2-infected A/J and control A/J mice, 2646 genes were differentially expressed (1469 upregulated; 1177 downregulated). Between SS2-infected B6 and control B6 mice, 1449 genes were differentially expressed (778 upregulated; 671 downregulated). These genes were analyzed for significant Gene Ontology (GO) categories and signaling pathways using the Kyoto Encylopedia of Genes and Genomes (KEGG) database to generate a signaling network. Upregulated genes in A/J and B6 mice were related to response to bacteria, immune response, positive regulation of B cell receptor signaling pathway, type I interferon biosynthesis, defense and inflammatory responses. Additionally, upregulated genes in SS2-infected B6 mice were involved in antigen processing and presentation of exogenous peptides, peptide antigen stabilization, lymphocyte differentiation regulation, positive regulation of monocyte differentiation, antigen receptor-mediated signaling pathway and positive regulation of phagocytosis. Downregulated genes in SS2-infected B6 mice played roles in glycolysis, carbohydrate metabolic process, amino acid metabolism, behavior and muscle regulation. Microarray results were verified by quantitative real-time PCR (qRT-PCR) of 14 representative deregulated genes. Four genes differentially expressed between SS2-infected A/J and B6 mice, toll-like receptor 2 (Tlr2), tumor necrosis factor (Tnf), matrix metalloproteinase 9 (Mmp9) and pentraxin 3 (Ptx3), were previously implicated in the response to S. suis infection. This study identified candidate genes that may influence susceptibility or resistance to SS2 infection in A/J and B6 mice, providing further validation of these models and contributing to understanding of S. suis pathogenic mechanisms.

Alzheimer's disease is characterized by the accumulation of amyloid-[beta] plaques, aggregation of hyperphosphorylated tau (pTau), and microglia activation. Galectin-3 (Gal3) is a [beta]-galactoside- binding protein that has been implicated in amyloid pathology. Its role in tauopathy remains enigmatic. Here, we showed that Gal3 was upregulated in the microglia of humans and mice with tauopathy. pTau triggered the release of Gal3 from human induced pluripotent stem cell-derived microglia in both its free and extracellular vesicular-associated (EV-associated) forms. Both forms of Gal3 increased the accumulation of pathogenic tau in recipient cells. Binding of Gal3 to pTau greatly enhanced tau fibrillation. Besides Gal3, pTau was sorted into EVs for transmission. Moreover, pTau markedly enhanced the number of EVs released by iMGL in a Gal3-dependent manner, suggesting a role of Gal3 in biogenesis of EVs. Single-cell RNA-Seq analysis of the hippocampus of a mouse model of tauopathy (THY-Tau22) revealed a group of pathogenic tau-evoked, Gal3- associated microglia with altered cellular machineries implicated in neurodegeneration, including enhanced immune and inflammatory responses. Genetic removal of Gal3 in THY-Tau22 mice suppressed microglia activation, reduced the level of pTau and synaptic loss in neurons, and rescued memory impairment. Collectively, Gal3 is a potential therapeutic target for tauopathy., Introduction Neuronal inclusions consisting of the microtubule-associated protein tau are found in various neurodegenerative diseases known as tauopathies. Alzheimer's disease (AD) is the most prevalent tauopathy and is characterized by [...]

Deep‐blue multi‐resonance (MR) emitters with stable and narrow full‐width‐at‐half‐maximum (FWHM) are of great importance for widening the color gamut of organic light‐emitting diodes (OLEDs). However, most planar MR emitters are vulnerable to intermolecular interactions from both the host and guest, causing spectral broadening and exciton quenching in thin films. Their emission in the solid state is environmentally sensitive, and the color purity is often inferior to that in solutions. Herein, a molecular design strategy is presented that simultaneously narrows the FWHM and suppresses intermolecular interactions by combining intramolecular locking and peripheral shielding within a carbonyl/nitrogen‐based MR core. Intramolecularly locking carbonyl/nitrogen‐based bears narrower emission of 2,10‐dimethyl‐12,12‐diphenyl‐4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐4,8(12H)‐dione in solution and further with peripheral‐shielding groups, deep‐blue emitter (12,12‐diphenyl‐2,10‐bis(9‐phenyl‐9H‐fluoren‐9‐yl)−4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐4,8(12H)‐dione, DPQAO‐F) exhibits ultra‐pure emission with narrow FWHM (c.a., 24 nm) with minimal variations (∆FWHM ≤ 3 nm) from solution to thin films over a wide doping range. An OLED based on DPQAO‐F presents a maximum external quantum efficiency (EQEmax) of 19.9% and color index of (0.134, 0.118). Furthermore, the hyper‐device of DPQAO‐F exhibits a record‐high EQEmax of 32.7% in the deep‐blue region, representing the first example of carbonyl/nitrogen‐based OLED that can concurrently achieve narrow bandwidth in the deep‐blue region and a high electroluminescent efficiency surpassing 30%. [ABSTRACT FROM AUTHOR]

Solar-driven CO2 reduction to yield high-value chemicals presents an appealing avenue for combating climate change, yet achieving selective production of specific products remains a significant challenge. We showcase two osmium complexes, przpOs, and trzpOs, as CO2 reduction catalysts for selective CO2-to-methane conversion. Kinetically, the przpOs and trzpOs exhibit high CO2 reduction catalytic rate constants of 0.544 and 6.41 s−1, respectively. Under AM1.5 G irradiation, the optimal Si/TiO2/trzpOs have CH4 as the main product and >90% Faradaic efficiency, reaching −14.11 mA cm−2 photocurrent density at 0.0 VRHE. Density functional theory calculations reveal that the N atoms on the bipyrazole and triazole ligands effectively stabilize the CO2-adduct intermediates, which tend to be further hydrogenated to produce CH4, leading to their ultrahigh CO2-to-CH4 selectivity. These results are comparable to cutting-edge Si-based photocathodes for CO2 reduction, revealing a vast research potential in employing molecular catalysts for the photoelectrochemical conversion of CO2 to methane. Solar-driven CO2 conversion to produce solar fuels is an attractive way to harness solar energy and reduce carbon emissions. Here, the authors report two osmium complexes as highly active and selective CO2 reduction catalysts for selective CO2-to-methane conversion on Si-based photocathodes. [ABSTRACT FROM AUTHOR]

Magnetic Weyl semimetal shows intriguing properties in both fundamental physics and potential applications. However, the complex relationship between nonreciprocal transmission and magnetic field manipulation in magnetic Weyl semimetal systems has not been generally clarified and fully utilized. Here, a universal Chirality–Wavevector–Magnetic field (C‐K‐B) relation is established in the magnetic Weyl semimetal system, which completely describes the spin topological band and its intrinsic polarization output in full space orientation under an arbitrary magnetic vector. This relation can provide complete guidance for the device design of nonreciprocal spin manipulation. Coupling this nonreciprocal mechanism with the photonic spin Hall effect of the geometric phased metasurface, a magnetic Weyl semimetal metasurface is constructed in the terahertz (THz) range, The experiments demonstrate the flexible THz beam steerings in a broad spatial dispersion range of ±25–±55° with four different working modes by only altering the biased magnetic vectors. Moreover, all these beam steering processes are accompanied by nonreciprocal isolating transmission with the isolation ratio reaching 27 dB. This C‐K‐B relation and active nonreciprocal beam steering devices are expected to prompt magneto‐optical devices and systems combined with echo isolation function in beam scanning, wavelength division multiplexing, and spin multiplexing. [ABSTRACT FROM AUTHOR]