Ultrathin and Biodegradable Bismuth Oxycarbonate Nanosheets with Massive Oxygen Vacancies for Highly Efficient Tumor Therapy.

Nanomaterials doped with high atom number elements can improve the efficacy of cancer radiotherapy, but their clinical application faces obstacles, such as being difficult to degrade in vivo, or still requiring relatively high radiation dose. In this work, a bismuth oxycarbonate-based ultrathin nanosheet with the thickness of 2.8 nm for safe and efficient tumor radiotherapy under low dose of X-ray irradiation is proposed. The high oxygen content (62.5% at%) and selective exposure of the facets of ultrathin 2D nanostrusctures facilitate the escape of large amounts of oxygen atoms on bismuth nanosheets from surface, forming massive oxygen vacancies and generating reactive oxygen species that explode under the action of X-rays. Moreover, the exposure of almost all atoms to environmental factors and the nature of oxycarbonates makes the nanosheets easily degrade into biocompatible species. In vivo studies demonstrate that nanosheets could induce apoptosis in cancer cells after low dose of X-ray irradiation without causing any damage to the liver or kidney. The tumor growth inhibition effect of radiotherapy increases from 49.88% to 90.76% with the help of bismuth oxycarbonate nanosheets. This work offers a promising future for nanosheet-based clinical radiotherapies of malignant cancers.

The Snf5-Hsf1 transcription module synergistically regulates stress responses and pathogenicity by maintaining ROS homeostasis in Sclerotinia sclerotiorum.

The SWI/SNF complex is guided to the promoters of designated genes by its co-operator to activate transcription in a timely and appropriate manner to govern development, pathogenesis, and stress responses in fungi. Nevertheless, knowledge of the complexes and their co-operator in phytopathogenic fungi is still fragmented. We demonstrate that the heat shock transcription factor SsHsf1 guides the SWI/SNF complex to promoters of heat shock protein (hsp) genes and antioxidant enzyme genes using biochemistry and pharmacology. This is accomplished through direct interaction with the complex subunit SsSnf5 under heat shock and oxidative stress. This results in the activation of their transcription and mediates histone displacement to maintain reactive oxygen species (ROS) homeostasis. Genetic results demonstrate that the transcription module formed by SsSnf5 and SsHsf1 is responsible for regulating morphogenesis, stress tolerance, and pathogenicity in Sclerotinia sclerotiorum, especially by directly activating the transcription of hsp genes and antioxidant enzyme genes counteracting plant-derived ROS. Furthermore, we show that stress-induced phosphorylation of SsSnf5 is necessary for the formation of the transcription module. This study establishes that the SWI/SNF complex and its co-operator cooperatively regulate the transcription of hsp genes and antioxidant enzyme genes to respond to host and environmental stress in the devastating phytopathogenic fungi.

1 H-NMR revealed pyruvate as a differentially abundant metabolite in the venom glands of Apis cerana and Apis mellifera.

As a common defense mechanism in Hymenoptera, bee venom has complex components. Systematic and comprehensive analysis of bee venom components can aid in early evaluation, accurate diagnosis, and protection of organ function in humans in cases of bee stings. To determine the differences in bee venom composition and metabolic pathways between Apis cerana and Apis mellifera, proton nuclear magnetic resonance (1 H-NMR) technology was used to detect the metabolites in venom samples. A total of 74 metabolites were identified and structurally analyzed in the venom of A. cerana and A. mellifera. Differences in the composition and abundance of major components of bee venom from A. cerana and A. mellifera were mapped to four main metabolic pathways: valine, leucine and isoleucine biosynthesis; glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; and the tricarboxylic acid cycle. These findings indicated that the synthesis and metabolic activities of proteins or polypeptides in bee venom glands were different between A. cerana and A. mellifera. Pyruvate was highly activated in 3 selected metabolic pathways in A. mellifera, being much more dominant in A. mellifera venom than in A. cerana venom. These findings indicated that pyruvate in bee venom glands is involved in various life activities, such as biosynthesis and energy metabolism, by acting as a precursor substance or intermediate product.

Anti-stokes luminescent organic nanoparticles for frequency upconversion biomedical imaging.

Frequency upconversion optical imaging has attracted great attention due to its remarkable advantages over traditional down-conversion optical imaging. However, the development of frequency upconversion optical imaging is extremely limited. Herein, five derivatives with BODIPY structure (B1-B5) were developed to investigate its frequency upconversion luminescence (FUCL) performance by introducing electron-donating and electron-withdrawing groups. Except for the nitro group decorated derivative, the other derivatives have strong and stable FUCL around 520 nm under 635 nm light excitation. More importantly, B5 retains FUCL ability after self-assembly. When applied to FUCL imaging of cells, B5 nanoparticles can be enriched in the cytoplasm and show a good signal-to-noise ratio. Meanwhile, FUCL tumor imaging can be achieved after 1 h of injection. This study not only provides a potential agent for FUCL biomedical imaging but also develops a new strategy for designing FUCL agents that exhibit excellent performance.

Comparison of spatiotemporal burial and contamination of heavy metals in core sediments of two plateau lakes with contrasting environments: implication for anthropogenic-driven processes.

Investigating the impacts of climatic factors and human activities on sedimentary records of heavy metal (HM) contamination in lakes is essential for decision-making in global environmental monitoring and assessment. Spatiotemporal distributions of grain size (GS) and HM (Al, Cr, Mn, Ni, Cu, Zn, As, and Pb) concentrations have been conducted in core sediments that are collected from two adjacent plateau fault-bound lakes in southwest China with contrasting environments, i.e., deep oligotrophic Lake Fuxian (FX) and shallow hypertrophic Lake Xingyun (XY). Results showed that the average value of d50 in FX (4.61 µm) was lower than that in XY (8.35 µm), but the average concentrations of HMs (except Cr and Mn) in XY were higher than those in FX. Heavy metal burial rates (HMBR) were mainly controlled by sediment accumulation rates (SARs) rather than HM concentrations. The correlation coefficients between GS and HM concentrations became strong as the increasing water depths were associated with a stable sedimentary environment. Time-integrated enrichment factors (EF) and source identification of HMs between FX and XY represented that Cr, Ni, and Cu originated from natural sources but Mn, Zn, As, and Pb from anthropogenic sources, respectively. Regardless of FX and XY, the transition times of HMs from natural to anthropogenic sources occurred in the mid-1960s. Comparison of qualification impacts of climatic factors and human-induced factors on increased anthropogenic HMBR by the partial least squares path modeling (PLS-PM) implied that socio-economic activities, such as population density (PD) and gross domestic product (GDP), provided higher contributors to increased anthropogenic HMBR in XY (0.23/0.71) than FX (0.11/0.18). The comparative results of this study provided new insights into environmental monitoring and management of HM contamination for adjacent lakes with contrasting environments.

Shedding Light on Luminescent Janus Nanoparticles: From Synthesis to Photoluminescence and Applications.

Luminescent Janus nanoparticles refer to a special category of Janus-based nanomaterials that not only exhibit dual-asymmetric surface nature but also attractive optical properties. The introduction of luminescence has endowed conventional Janus nanoparticles with many alluring light-responsive functionalities and broadens their applications in imaging, sensing, nanomotors, photo-based therapy, etc. The past few decades have witnessed significant achievements in this field. This review first summarizes well-established strategies to design and prepare luminescent Janus nanoparticles and then discusses optical properties of luminescent Janus nanoparticles based on downconversion and upconversion photoluminescence mechanisms. Various emerging applications of luminescent Janus nanoparticles are also introduced. Finally, opportunities and future challenges are highlighted with respect to the development of next-generation luminescent Janus nanoparticles with diverse applications.

N-myc and STAT interactor is a novel biomarker of severity in community-acquired pneumonia: a prospective study.

OBJECTIVES: To tested the ability of N-myc and STAT interactor (NMI) levels in patients with community-acquired pneumonia (CAP) to predict the severity of the disease. METHODS: Prospective observational analysis of patients with CAP was performed. The NMI levels in serum of 394 CAP patients on admission were measured by immunoassay. Thirty-day mortality and intensive care unit (ICU) admission were set as clinical outcomes. The predicting value of NMI for clinical outcomes was determined by receiver operating characteristic curve and logistic regression analysis. The internal validity was assessed using cross-validation with bootstrap resampling. RESULTS: NMI was an independent risk factor for both 30-day mortality and admission to ICU for CAP patients. The area under curve (AUC) of NMI to predict mortality was 0.91 (95% CI: 0.86-0.96), and that to predict ICU admission was 0.92 (95% CI: 0.88-0.97), significantly higher than that of other biomarkers including procalcitonin and C-reactive protein. The proportion of clinical outcomes notably rose as NMI levels elevated (P < 0.001). The AUCs of the new score systems including NMI (N-PSI and N-CURB65 score) to predict outcomes were significantly higher than the original score systems. CONCLUSIONS: NMI is a novel biomarker for predicting CAP severity superior to former biomarkers in 30-day mortality and ICU admission.

Sensitivity and Resistance Risk Assessment of Fusarium graminearum from Wheat to Prothioconazole.

Fusarium head blight (FHB), caused mainly by Fusarium graminearum, is one of the most devastating diseases of wheat. Prothioconazole is a broad-spectrum demethylation inhibitor fungicide with excellent efficacy against FHB. In this study, 235 strains of F. graminearum collected from different regions of Henan Province of China in 2016, 2017, and 2018 were randomly selected. The sensitivity of F. graminearum to prothioconazole was determined by the mycelial growth inhibition method. The results showed that the half maximal effective concentration (EC50) values of F. graminearum to prothioconazole ranged from 0.4742 to 3.4403 µg/ml, and the average EC50 value was 1.7758 ± 0.6667 µg/ml. The sensitivity frequency distribution presented a consequent unimodal curve, and thus the average EC50 value can be established as the baseline sensitivity of F. graminearum to prothioconazole. Ten strains of prothioconazole-resistant mutants were obtained by fungicide taming, and the resistance factor of the mutants ranged from 5.71 to 12.32. The genetic stability assay showed that resistance can be inherited stably for 10 generations. All mutants displayed different degrees of defects in vegetative growth, conidia formation, and pathogenicity compared with the parental strain. These results indicated that F. graminearum has a low risk of resistance to prothioconazole. Cross-resistance assay showed that no cross-resistance was found between prothioconazole and carbendazim, tebuconazole, phenamacril, and pydiflumetofen. Among all mutants, sequence analysis showed that no mutation site was found in cyp51A and cyp51B. Real-time PCR assays showed that the expression levels of cyp51A and cyp51B of the mutants were significantly increased after prothioconazole treatment for 24 h. In summary, our study provided a theoretical basis for the resistance risk assessment of F. graminearum to prothioconazole and scientific application of prothioconazole in controlling FHB.

Engineered lanthanide-doped upconversion nanoparticles for biosensing and bioimaging application.

Various fluctuations of intracellular ions, biomolecules, and other conditions in the physiological environment play crucial roles in fundamental biological processes. These factors are of great importance for analysis in biomedical detection. Nevertheless, developments of the simple, rapid, and accurate proof for specific detection still encounter major challenges. Upconversion nanoparticles (UCNPs), which could absorb multiple low-energy near-infrared light (NIR) photon excitation and emits high-energy photons caused by anti-Stokes shift, show unique upconversion luminescence (UCL) properties, for example, sharp emission band, high physicochemical stability like near-zero photobleaching, photo blinking in biological tissues, and long luminescence lifetime. Furthermore, the NIR used for the light source to excite UCNPs enable lower photo-damage effect and deeper penetration of tissue, and in the meantime, it can avoid the auto-fluorescence and light scattering from biological tissue interference. Thus, the lanthanide-doped UCNP-based functional platform with controlled structure, crystalline phase, size, and multicolor emission has become an appropriate nanomaterial for bioapplications such as biosensing, bioimaging, drug release, and therapies. In this review, the recent progress about synthesis and biomedical applications of UCNPs related to sensing and bioimaging is summarized. Firstly, the different luminescence mechanisms of the upconversion process are presented. Secondly, four of the most common methods for synthesizing UCNPs are compared as well as the advantages and disadvantages of these synthetic routes. Meanwhile, the surface modification of lanthanide-doped UCNPs was introduced to pave the way for their biochemistry applications. Next, this review detailed the biological applications of lanthanide-doped UCNPs, particularly in bioimaging, including UCL and multi-modal imaging and biosensing (monitoring intracellular ions and biomolecules). Finally, the challenges and future perspectives in materials science and biomedical fields of UCNPs are concluded: the low quantum yield of the upconversion process should be considered when they are executed as imaging contrast agents. And the biosafety of lanthanide-doped UCNPs needs to be evaluated.

A novel dual-flux immunochromatographic test strip based on luminescence resonance energy transfer for simultaneous detection of ochratoxin A and deoxynivalenol.

Mycotoxins are secondary metabolites of fungi, which seriously threaten human health. Among them, ochratoxin A (OTA) and deoxynivalenol (DON) have become the main factors that pollute cereals and by-products. In order to achieve simultaneous detection of OTA and DON quantitatively, a novel dual-flux immunochromatographic assay (dICA) was established. The dual-flux assay is based on upconversion nanoparticles (UCNPs) as fluorescence tags to label antigens and gold nanoparticles (AuNPs) as fluorescence quencher to label monoclonal antibodies (mAbs). The intensity of the green fluorescence (540 nm) of UCNPs can be used as an analytical signal, indicating the formation of antigen-antibody immune complexes, thereby indicating the presence or absence of the target analyte. The intensity of the red fluorescence (660 nm) of UCNPs is not affected and can be used as a quality control signal, and the dual-flux bidirectional single-line labeling mode allows for the simultaneous detection of two different mycotoxins on two test lines. This work indicated that the developed dICA provided a sensitive, rapid, and reliable on-site simultaneous detection of multiple mycotoxins.

Single-Line Flow Assay Platform Based on Orthogonal Emissive Upconversion Nanoparticles.

Lateral flow assay (LFA) has played pivotal roles in many emergency public safety incidents, such as coronavirus disease diagnostics; however, the present double-line (test and control line) design strategy for LFA strips greatly restricts their applications in high-throughput quantitative analysis because the limited sample diffusion distance on the strips constrains the number of test/control lines. Herein, a novel single-line-based LFA (sLFA) strip, which combines test and control line, is developed by exploiting an orthogonal emissive upconversion nanoparticle (UCNP) as a signal reporter on the test line, where one emission can be used as a reporting signal and the other as a calibrating signal. This UCNP-based test line with an interior reference also can play a validating role as a control line, and hence capturing antibodies are not needed for control lines, greatly saving fabrication costs. As a proof-of-concept, this novel sLFA strip is successfully explored to accurately and rapidly detect aflatoxin B1. Moreover, due to the removal of control lines, such a novel strategy greatly reduces the strip size, facilitating the design of a testing array for multiple detections of different samples. The test line herein is designed in a ring shape, and several test rings are assembled to be a chip for the testing of multiple samples. To our knowledge, this is the first demonstration of single-line-based LFA strips, which will significantly improve the detection capacities and accuracies and reduce the testing costs of LFA strips in real sample applications ranging from food analysis to in vitro diagnostics.

Tumor Microenvironment Modulation Platform Based on Composite Biodegradable Bismuth-Manganese Radiosensitizer for Inhibiting Radioresistant Hypoxic Tumors.

Solid tumors possess a unique internal environment with high-level thiols (mainly glutathione), over-expressed H2 O2 , and low oxygen partial pressure, which severely restrict the radiotherapy (RT) efficacy. To overcome the imperfections of RT alone, there is vital to design a multifunctional radiosensitizer that simultaneously achieves multimodal therapy and tumor microenvironment (TME) regulation. Bismuth (Bi)-based nanospheres are wrapped in the MnO2 layer to form core-shell-structured radiosensitizer (Bi@Mn) that can effectively load docetaxel (DTX). The solubility of Bi@Mn-DTX is further improved via folic acid-modified amphiphilic polyethylene glycol (PFA). Bi@Mn-DTX-PFA can specifically respond to the TME to realize multimodal therapy. Primarily, the outer MnO2 layer responds with H2 O2 and glutathione to release oxygen and generate •OH, thereby alleviating hypoxia and achieving chemodynamic therapy (CDT). Afterward, the strong coordination between Bi3+ and deprotonated thiol groups in glutathione allows the mesoporous Bi-containing core bonding with glutathione to form a water-soluble complex. These actions conduce Bi@Mn-DTX-PFA degradation, further releasing DTX to implement chemotherapy (CHT). In addition, the degradation in vivo and tumor enrichment of Bi@Mn-PFA are explored via T1 -weighted magnetic resonance and computed tomography imaging. The biodegradable composite Bi@Mn-DTX-PFA can simultaneously modulate the TME and achieve multimodal treatment (RT/CDT/CHT) for hypoxic tumors.

Improved light output from thick ß-Ga2O3 scintillation crystals via graded-refractive-index photonic crystals.

ß-Ga2O3 is a promising candidate as a fast scintillation crystal for radiation detection in fast X-ray imaging and high-energy physics experiments. However, total internal reflection severely limits its light output. Conventional photonic crystals can improve the light output, but such improvement decreases dramatically with increased scintillator thickness due to the strong backward reflection by the photonic crystals. Here, graded-refractive-index photonic crystals composed of nanocone arrays are designed and fabricated on the surfaces of ß-Ga2O3 crystals with various thicknesses. Compared to the conventional photonic crystals, there is still an obvious light output improvement by using the graded-refractive-index photonic crystals when the thickness of the crystals is increased by three times. The effect of thickness on the improved light output is investigated with numerical simulations and experiments. Overall, the graded-refractive-index photonic crystals are beneficial to the improvement of light output from thick scintillators.

Light output enhancement of scintillators by using mixed-scale microstructures.

Scintillators play an important role in the field of nuclear radiation detection. However, the light output of the scintillators is often limited by total internal reflection due to the high refractive indices of the scintillators. Furthermore, the light emission from scintillators typically has an approximately Lambertian profile, which is detrimental to the collection of the light. In this paper, we demonstrate a promising method to achieve enhancement of the light output from scintillators through use of mixed-scale microstructures that are composed of a photonic crystal slab and a microlens array. Simulations and experimental results both show significant improvements in the scintillator light output. The X-ray imaging characteristics of scintillators are improved by the application of the mixed-scale microstructures. The results presented here suggest that the application of the proposed mixed-scale microstructures to scintillators will be beneficial in the nuclear radiation detection field.

Lanthanide-Doped Nanoparticles for Near-Infrared Light Activation of Photopolymerization: Fundamentals, Optimization and Applications.

Photopolymerization refers to a type of polymerization process in which light is utilized as excitation source to initiate polymerization of monomers and oligomers. Despite great progress, photopolymerization is typically induced by ultraviolet or visible light, which still greatly restrains its applications. Upconversion nanoparticles (UCNPs) represent a class of optical nanomaterials that are able to convert low-energy near-infrared (NIR) light into high-energy ultraviolet (or visible light) emissions. In this context, UCNP-assisted photopolymerization has recently attracted extensive attentions due to its unique advantages. In this account, recent advances in the fundamentals, optimization and emerging applications of UCNP-based photopolymerization are reviewed. Fundamental theories of upconversion luminescence and photopolymerization will be introduced first. Various optimization approaches to improve UCNP-assisted photopolymerization are then summarized, followed by diverse emerging applications. Challenges and future perspectives in this area will be provided as a conclusion.

FGFF Descriptor and Modified Hu Moment-Based Hand Gesture Recognition.

Gesture recognition has been studied for decades and still remains an open problem. One important reason is that the features representing those gestures are not sufficient, which may lead to poor performance and weak robustness. Therefore, this work aims at a comprehensive and discriminative feature for hand gesture recognition. Here, a distinctive Fingertip Gradient orientation with Finger Fourier (FGFF) descriptor and modified Hu moments are suggested on the platform of a Kinect sensor. Firstly, two algorithms are designed to extract the fingertip-emphasized features, including palm center, fingertips, and their gradient orientations, followed by the finger-emphasized Fourier descriptor to construct the FGFF descriptors. Then, the modified Hu moment invariants with much lower exponents are discussed to encode contour-emphasized structure in the hand region. Finally, a weighted AdaBoost classifier is built based on finger-earth mover's distance and SVM models to realize the hand gesture recognition. Extensive experiments on a ten-gesture dataset were carried out and compared the proposed algorithm with three benchmark methods to validate its performance. Encouraging results were obtained considering recognition accuracy and efficiency.

Convenient method for improving the light output of scintillators by using buffer layers coated with photonic crystals.

The low light-extraction efficiency of scintillators is due to total internal reflection and has led to the extensive use of photonic crystals to improve the light output. However, in some applications, photonic crystals cannot be fabricated directly on scintillators. Here, we demonstrate a promising method to improve the light output of scintillators by using a buffer layer coated with photonic crystals and then fixed to the scintillator. Through both numerical simulations and experiments, we investigate how the refractive indexes of the buffer layer and photonic crystal affect the light output from scintillators. The experimental results indicate that the light output of (Lu,Y)2SiO5:Ce scintillators is enhanced 1.9 times by using a sapphire buffer layer coated with an array of polystyrene nanospheres. This method can be used to improve the detection efficiency of radiation-detection systems when photonic crystals cannot be fabricated directly on the scintillator.

Fabrication of 2D-2D Heterojunction Catalyst with Covalent Organic Framework (COF) and MoS2 for Highly Efficient Photocatalytic Degradation of Organic Pollutants.

In this work, for the first time, we fabricated a novel covalent organic framework (COF)-based 2D-2D heterojunction composite MoS2/COF by a facile hydrothermal method. The results of photocatalytic degradation of TC and RhB under simulated solar light irradiation showed that the as-prepared composite exhibited outstanding catalytic efficiency compared with pristine COFs and MoS2. The significantly enhanced catalytic efficiency can be ascribed to the formation of 2D-2D heterojunction with a well-matched band position between COF and MoS2, which can effectively restrain the recombination of charge carriers and increase the light absorption as well as the specific surface area. Moreover, the fabricated 2D-2D layered structure can effectively increase the contact area with an intimate interface contact, which greatly facilitates the charge mobility and transfer in the interfaces. This study reveals that artful integration of organic (COFs) and inorganic materials into a single hybrid with a 2D-2D interface is an effective strategy to fabricate highly efficient photocatalysts.

Fabrication of Hierarchical Co9S8@ZnAgInS Heterostructured Cages for Highly Efficient Photocatalytic Hydrogen Generation and Pollutants Degradation.

In the present study, a hierarchical Co9S8@ZnAgInS heterostructural cage was developed for the first time which can photocatalytically produce hydrogen and degrade organic pollutants with high efficiency. First, the Co9S8 dodecahedron was synthesized using a metal-organic framework (MOFs) material, ZIF-67, as a precursor, then two kinds of metal sulfide semiconductors were elaborately integrated into a hierarchical hollow heterostructural cage with coupled heterogeneous shells and 2D nanosheet subunits. The artfully designed hollow heterostructural composite exhibited remarkable photocatalytic activity without using any cocatalysts, with a 9395.3 µmol g-1 h-1 H2 evolution rate and high degradation efficiency for RhB. The significantly enhanced photocatalytic activity can be attributed to the unique architecture and intimate-contact interface between Co9S8 and ZnAgInS, which promote the transfer and separation of the photogenerated charges, increase light absorption, and offer large surface area and active sites. This work presents a new strategy to design highly active semiconductor photocatalysts by using MOF materials as precursors and coupling of metal sulfide semiconductors to form hollow architecture dodecahedron cages with an intimate interface.

A Hypothesis-Generating Study of the Combination of Aspirin plus Macrolides in Patients with Severe Community-Acquired Pneumonia.

While the inflammatory response to severe pneumonia is paramount in limiting and resolving the infection, excessive inflammation can lead to deleterious effects. We theorized that patients with severe community-acquired pneumonia (CAP) who were treated with macrolides and aspirin would receive benefit beyond that of conventional antibiotic therapy. An observational study was conducted with patients with severe CAP. All patients were admitted to 5 teaching hospitals (in Italy, the United States, Japan, and China), and data were gathered from their electronic medical records. Severe pneumonia was defined according to Infectious Diseases Society of America/American Thoracic Society criteria. Patients were divided into 4 groups, i.e., (i) the aspirin-only group (ASG), (ii) the macrolide-only group (MG), (iii) the aspirin plus macrolide group (ASMG), or (iv) the neither aspirin nor macrolide group (NASMG). Survival rates for the 4 groups were evaluated after adjustment for confounders and after weighting by propensity score. A total of 1,295 patients were included in the analysis. There were 237 patients (18.3%) in the ASG, 294 (22.7%) in the MG, 148 (11.4%) in the ASMG, and 616 (47.6%) in the NASMG. The mortality rate at 30 days was 15.5% in the ASMG, compared to 28.2% in the NASMG, 23.8% in the MG, and 21.1% in the ASG. After propensity score analysis, receipt of aspirin plus macrolide (hazard ratio, 0.71 [95% confidence interval, 0.58 to 0.88]; P = 0.002) was associated with a higher 30-day survival rate. This is a hypothesis-generating study in which data suggest that the combination of aspirin plus a macrolide improves 30-day survival rates for patients with severe CAP. Further randomized studies will need to be undertaken to confirm this phenomenon.