High-temperature bulk metallic glasses developed by combinatorial methods.

Since their discovery in 19601, metallic glasses based on a wide range of elements have been developed2. However, the theoretical prediction of glass-forming compositions is challenging and the discovery of alloys with specific properties has so far largely been the result of trial and error3-8. Bulk metallic glasses can exhibit strength and elasticity surpassing those of conventional structural alloys9-11, but the mechanical properties of these glasses are critically dependent on the glass transition temperature. At temperatures approaching the glass transition, bulk metallic glasses undergo plastic flow, resulting in a substantial decrease in quasi-static strength. Bulk metallic glasses with glass transition temperatures greater than 1,000 kelvin have been developed, but the supercooled liquid region (between the glass transition and the crystallization temperature) is narrow, resulting in very little thermoplastic formability, which limits their practical applicability. Here we report the design of iridium/nickel/tantalum metallic glasses (and others also containing boron) with a glass transition temperature of up to 1,162 kelvin and a supercooled liquid region of 136 kelvin that is wider than that of most existing metallic glasses12. Our Ir-Ni-Ta-(B) glasses exhibit high strength at high temperatures compared to existing alloys: 3.7 gigapascals at 1,000 kelvin9,13. Their glass-forming ability is characterized by a critical casting thickness of three millimetres, suggesting that small-scale components for applications at high temperatures or in harsh environments can readily be obtained by thermoplastic forming14. To identify alloys of interest, we used a simplified combinatorial approach6-8 harnessing a previously reported correlation between glass-forming ability and electrical resistivity15-17. This method is non-destructive, allowing subsequent testing of a range of physical properties on the same library of samples. The practicality of our design and discovery approach, exemplified by the identification of high-strength, high-temperature bulk metallic glasses, bodes well for enabling the discovery of other glassy alloys with exciting properties.

Atomic-Scale In Situ Observations of Reversible Phase Transformation Assisted Twinning in a CrCoNi Medium-Entropy Alloy.

Twinning is an important deformation mode of face-centered-cubic (FCC) medium- and high-entropy alloys, especially under extreme loading conditions. However, the twinning mechanism in these alloys that have a low or even negative stacking fault energy remains debated. Here, we report atomic-scale in situ observations of the deformation process of a prototypical CrCoNi medium-entropy alloy under tension. We found that the parent FCC phase first transforms into a hexagonal close-packed (HCP) phase through Shockley partial dislocations slipping on the alternate {111} planes. Subsequently, the HCP phase rapidly changes to an FCC twin band. Such reversible phase transformation assisted twinning is greatly promoted by external tensile loads, as elucidated by geometric phase analysis. These results indicate the previously underestimated role of the metastable HCP phase in nanotwin nucleation and early plastic deformations of CrCoNi alloys and shed light on microstructure regulation of medium-entropy alloys with enhanced mechanical properties.

Tuning Electrocatalytic Activities of Dealloyed Nanoporous Catalysts by Macroscopic Strain Engineering.

It is technically challenging to quantitatively apply strains to tune catalysis because most heterogeneous catalysts are nanoparticles, and lattice strains can only be applied indirectly via core-shell structures or crystal defects. Herein, we report quantitative relations between macroscopic strains and hydrogen evolution reaction (HER) activities of dealloyed nanoporous gold (NPG) by directly applying macroscopic strains upon bulk NPG. It was found that macroscopic compressive strains lead to a decrease, while macroscopic tensile strains improve the HER activity of NPG, which is in line with the d-band center model. The overpotential and onset potential of HER display approximately a linear relation with applied macroscopic strains, revealing an ∼2.9 meV decrease of the binding energy per 0.1% lattice strains from compressive to tensile. The methodology with the high strain sensitivity of electrocatalysis, developed in this study, paves a new way to investigate the insights of strain-dependent electrocatalysis with high precision.

Melatonin suppresses TLR4-mediated RSV infection in the central nervous cells by inhibiting NLRP3 inflammasome formation and autophagy.

Respiratory syncytial virus (RSV) infects neuronal cells in the central nervous system (CNS), resulting in neurological symptoms. In the present study, we intended to explore the mechanism of RSV infection-induced neuroinflammatory injury from the perspective of the immune response and sought to identify effective protective measures against the injury. The findings showed that toll-like receptor 4 (TLR4) was activated after RSV infection in human neuronal SY5Y cells. Furthermore, TLR4 activation induced autophagy and apoptosis in neuronal cells, promoted the formation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and increased the secretion of downstream inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-18 (IL-18) and tumour necrosis factor-α (TNF-α). Interestingly, blockade of TLR4 or treatment with exogenous melatonin significantly suppressed TLR4 activation as well as TLR4-mediated apoptosis, autophagy and immune responses. Therefore, we infer that melatonin may act on the TLR4 to ameliorate RSV-induced neuronal injury, which provides a new therapeutic target for RSV infection.

Plasma genome-wide mendelian randomization identifies potentially causal genes in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease with a very poor prognosis. Existing drugs for the treatment of IPF are still insufficient. Therefore, there is still a need to explore new drug targets for preventing and treating IPF. METHODS: We included quantitative trait loci (QTL) for genes, DNA methylation, and proteins in plasma, as well as the summary statistics for IPF. Genetic variants located within 500 kb of the gene and strongly associated with plasma exposure were used as instrumental variables. The causal association between plasma exposures and IPF was primarily estimated using summary-data-based Mendelian randomization (SMR) analysis. Five other MR methods and sensitivity analyses were employed to validate the SMR results. Bayesian tests for colocalization between QTL and IPF risk loci further strengthen the MR results. RESULTS: We identified three genes and five DNA methylation sites causally associated with IPF by SMR analysis, validation of MR analysis, sensitivity analysis, and colocalization analysis. BTRC and LINC01252 were negatively associated with IPF risk (OR: 0.30, 95% CI: 0.17-0.54, FDRSMR = 0.029; OR: 0.85, 95% CI: 0.78-0.92, FDRSMR = 0.043), and RIPK4 was positively associated with IPF risk (OR: 2.60, 95% CI: 1.64-4.12, FDRSMR = 0.031). cg00045227 (OR8U8, OR: 1.16, 95% CI: 1.08-1.24, FDRSMR = 0.010), cg00577578 (GBAP1, OR: 1.23, 95% CI: 1.12-1.36, FDRSMR = 0.014), cg14222479 (ARPM1, OR: 3.17, 95% CI: 1.98-5.08, FDRSMR = 0.001), and cg19263494 (PMF1, OR: 1.20, 95% CI: 1.10-1.30, FDRSMR = 0.012) were positively associated with the risk of IPF, whereas cg07163735 (MAPT, OR: 0.22, 95% CI: 0.11-0.45, FDRSMR = 0.013) was negatively correlated with the risk of IPF. CONCLUSIONS: This study demonstrated that genetically determined plasma levels of the BTRC, RIPK4, and LINC01252 genes, as well as methylation levels of cg00045227 (OR8U8), cg00577578 (GBAP1), cg07163735 (MAPT), cg14222479 (ARPM1), and cg19263494 (PMF1), have causal influences on the risk of IPF.

Highly diverse sputum microbiota correlates with the disease severity in patients with community-acquired pneumonia: a longitudinal cohort study.

BACKGROUND: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. METHODS: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. RESULTS: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. CONCLUSION: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

MTF1 genetic variants are associated with lung cancer risk in the Chinese Han population.

BACKGROUND: Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored. METHODS: The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk. RESULTS: MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers. CONCLUSIONS: We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.

Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial.

AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.

Association between body roundness index and prevalence of kidney stone in the U.S: a study based on the NHANES database.

OBJECTIVE: This study aimed to evaluate the potential association between the body roundness index (BRI) and kidney stone prevalence in adults in the United States. METHODS: A cohort of participants from the National Health and Nutrition Examination Survey (NHANES) database spanning 2007-2018 were gathered for analysis. Logistic regression analyses, subgroup assessments, and calculations were employed to examine the potential link between BRI and kidney stone prevalence. RESULTS: The study included 30,990 participants aged > 20 years, of which 2,891 declared a kidney stone history. After modulating all relevant confounding factors, each unit increase in the BRI was linked to a 65% increase in kidney stone prevalence (OR = 1.65, 95% CI: 1.47, 1.85). Sensitivity analyses conducted by categorizing the BRI into three groups revealed a 59% increase in kidney stone prevalence in the highest tertile BRI group compared to the lowest one (OR = 1.59, 95% CI: 1.42, 1.79). Furthermore, dose-response curves depicted a positive near-linear correlation between the BRI and the risk of kidney stone prevalence. CONCLUSION: These findings suggest a clinically noteworthy positive correlation between higher BRI values and kidney stone prevalence among the studied US adult population. However, it is essential to acknowledge that the observed relationship does not establish a causal link.

Decoupling between Shockley partials and stacking faults strengthens multiprincipal element alloys.

Mechanical properties are fundamental to structural materials, where dislocations play a decisive role in describing their mechanical behavior. Although the high-yield stresses of multiprincipal element alloys (MPEAs) have received extensive attention in the last decade, the relation between their mechanistic origins remains elusive. Our multiscale study of density functional theory, atomistic simulations, and high-resolution microscopy shows that the excellent mechanical properties of MPEAs have diverse origins. The strengthening effects through Shockley partials and stacking faults can be decoupled in MPEAs, breaking the conventional wisdom that low stacking fault energies are coupled with wide partial dislocations. This study clarifies the mechanistic origins for the strengthening effects, laying the foundation for physics-informed predictive models for materials design.

Homogeneous antibody and CAR-T cells with improved effector functions targeting SSEA-4 glycan on pancreatic cancer.

Pancreatic cancer is usually asymptomatic in the early stages; the 5-y survival rate is around 9%; and there is a lack of effective treatment. Here we show that SSEA-4 is more expressed in all pancreatic cancer cell lines examined but not detectable in normal pancreatic cells; and high expression of SSEA-4 or the key enzymes B3GALT5 + ST3GAL2 associated with SSEA-4 biosynthesis significantly lowers the overall survival rate. To evaluate potential new treatments for pancreatic cancer, homogeneous antibodies with a well-defined Fc glycan for optimal effector functions and CAR-T cells with scFv construct designed to target SSEA-4 were shown highly effective against pancreatic cancer in vitro and in vivo. This was further supported by the finding that a subpopulation of natural killer (NK) cells isolated by the homogeneous antibody exhibited enhancement in cancer-cell killing activity compared to the unseparated NK cells. These results indicate that targeting SSEA-4 by homologous antibodies or CAR-T strategies can effectively inhibit cancer growth, suggesting SSEA-4 as a potential immunotherapy target for treating pancreatic disease.

Deciphering evolutionary dynamics of WRKY genes in Arachis species.

BACKGROUND: Cultivated peanut (Arachis hypogaea), a progeny of the cross between A. duranensis and A. ipaensis, is an important oil and protein crop from South America. To date, at least six Arachis genomes have been sequenced. WRKY transcription factors (TFs) play crucial roles in plant growth, development, and response to abiotic and biotic stresses. WRKY TFs have been identified in A. duranensis, A. ipaensis, and A. hypogaea cv. Tifrunner; however, variations in their number and evolutionary patterns across various Arachis spp. remain unclear. RESULTS: WRKY TFs were identified and compared across different Arachis species, including A. duranensis, A. ipaensis, A. monticola, A. hypogaea cultivars (cv.) Fuhuasheng, A. hypogaea cv. Shitouqi, and A. hypogaea cv. Tifrunner. The results showed that the WRKY TFs underwent dynamic equilibrium between diploid and tetraploid peanut species, characterized by the loss of old WRKY TFs and retention of the new ones. Notably, cultivated peanuts inherited more conserved WRKY orthologs from wild tetraploid peanuts than their wild diploid donors. Analysis of the W-box elements and protein-protein interactions revealed that different domestication processes affected WRKY evolution across cultivated peanut varieties. WRKY TFs of A. hypogaea cv. Fuhuasheng and Shitouqi exhibited a similar domestication process, while those of cv. Tifrunner of the same species underwent a different domestication process based on protein-protein interaction analysis. CONCLUSIONS: This study provides new insights into the evolution of WRKY TFs in Arachis spp.

Lateral metabolome study reveals the molecular mechanism of cytoplasmic male sterility (CMS) in Chinese cabbage.

BACKGROUND: Chinese cabbage is one of the most widely grown leafy vegetables in China. Cytoplasmic male sterility (CMS) is a maternally inherited trait that produces abnormal pollen during anther development, which is commonly seen in cruciferous vegetables. However, the molecular mechanism of Chinese cabbage CMS is not clear. In this study, the metabolome and hormone profiles of Chinese cabbage male sterile line (CCR20000) and sterile maintainer line (CCR20001) were analyzed in flower buds during normal stamen development and abnormal stamen development, respectively. RESULTS: A total of 556 metabolites were detected based on UPLC-MS/MS detection platform and database search, and the changes of hormones such as auxin, cytokinins, abscisic acid, jasmonates, salicylic acid, gibberellin acid and ethylene were analyzed. The results showed that compared with the male fertile line (MF), the male sterile line (MS) significantly decreased the content of flavonoids and phenolamides metabolites in the stamen dysplasia stage, accompanied by a large accumulation of glucosinolate metabolites. Meanwhile, the contents of GA9, GA20, IBA, tZ and other hormones in MS were significantly lower than those in MF strains. Further, by comparing the metabolome changes of MF and MS during stamen dysplasia, it was found that flavonoid metabolites and amino acid metabolites were distinctly different. CONCLUSIONS: These results suggest that flavonoids, phenolamides and glucosinolate metabolites may be closely related to the sterility of MS strains. This study provides an effective basis for further research on the molecular mechanism of CMS in Chinese cabbage.

Stereolithography 3D Printed Carbon Microlattices with Hierarchical Porosity for Structural and Functional Applications.

Hierarchically porous carbon microlattices (HPCMLs) fabricated by using a composite photoresin and stereolithography (SLA) 3D printing is reported. Containing magnesium oxide nanoparticles (MgO NPs) as porogens and multilayer graphene nanosheets as UV-scattering inhibitors, the composite photoresin is formed to simple cubic microlattices with digitally designed porosity of 50%. After carbonization in vacuum at 1000 °C and chemical removal of MgO NPs, it is realized that carbon microlattices possessing hierarchical porosity are composed of the lattice architecture (≈100 µm), macropores (≈5 µm), mesopores (≈50 nm), and micropores (≈1 nm). The linear shrinkage after pyrolysis is as small as 33%. Compressive strength of 7.45 to 10.45 MPa and Young's modulus of 375 to 736 MPa are achieved, proving HPCMLs a robust mechanical component among reported carbon materials with a random pore structure. Having a few millimeters in thickness, the HPCMLs can serve as thick supercapacitor electrodes that demonstrate gravimetric capacitances 105 and 13.8 F g-1 in aqueous and organic electrolyte, reaching footprint areal capacitances beyond 10 and 1 F cm-2 , respectively. The results present that the composite photoresin for SLA can yield carbon microarchitectures that integrate structural and functional properties for structural energy storages .

Universal scaling law of glass rheology.

The similarity in atomic/molecular structure between liquids and glasses has stimulated a long-standing hypothesis that the nature of glasses may be more fluid-like, rather than the apparent solid. In principle, the nature of glasses can be characterized by the dynamic response of their rheology in a wide rate range, but this has not been realized experimentally, to the best of our knowledge. Here we report the dynamic response of shear stress to the shear strain rate of metallic glasses over a timescale of nine orders of magnitude, equivalent to hundreds of years, by broadband stress relaxation experiments. The dynamic response of the metallic glasses, together with other 'glasses', follows a universal scaling law within the framework of fluid dynamics. The universal scaling law provides comprehensive validation of the conjecture on the jamming (dynamic) phase diagram by which the dynamic behaviours of a wide variety of 'glasses' can be unified under one rubric parameterized by the thermodynamic variables of temperature, volume and stress in the trajectory space.

Genetic association of circulating C-reactive protein levels with idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study.

BACKGROUND: Several observational studies have found that idiopathic pulmonary fibrosis (IPF) is often accompanied by elevated circulating C-reactive protein (CRP) levels. However, the causal relationship between them remains to be determined. Therefore, our study aimed to explore the causal effect of circulating CRP levels on IPF risk by the two-sample Mendelian randomization (MR) analysis. METHODS: We analyzed the data from two genome-wide association studies (GWAS) of European ancestry, including circulating CRP levels (204,402 individuals) and IPF (1028 cases and 196,986 controls). We primarily used inverse variance weighted (IVW) to assess the causal effect of circulating CRP levels on IPF risk. MR-Egger regression and MR-PRESSO global test were used to determine pleiotropy. Heterogeneity was examined with Cochran's Q test. The leave-one-out analysis tested the robustness of the results. RESULTS: We obtained 54 SNPs as instrumental variables (IVs) for circulating CRP levels, and these IVs had no significant horizontal pleiotropy, heterogeneity, or bias. MR analysis revealed a causal effect between elevated circulating CRP levels and increased risk of IPF (ORIVW = 1.446, 95% CI 1.128-1.854, P = 0.004). CONCLUSIONS: The present study indicated that elevated circulating CRP levels could increase the risk of developing IPF in people of European ancestry.

Identification of priority pathogens for aetiological diagnosis in adults with community-acquired pneumonia in China: a multicentre prospective study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. METHODS: A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. RESULTS: Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP. CONCLUSIONS: The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.

Ultrastrong steel via minimal lattice misfit and high-density nanoprecipitation.

Next-generation high-performance structural materials are required for lightweight design strategies and advanced energy applications. Maraging steels, combining a martensite matrix with nanoprecipitates, are a class of high-strength materials with the potential for matching these demands. Their outstanding strength originates from semi-coherent precipitates, which unavoidably exhibit a heterogeneous distribution that creates large coherency strains, which in turn may promote crack initiation under load. Here we report a counterintuitive strategy for the design of ultrastrong steel alloys by high-density nanoprecipitation with minimal lattice misfit. We found that these highly dispersed, fully coherent precipitates (that is, the crystal lattice of the precipitates is almost the same as that of the surrounding matrix), showing very low lattice misfit with the matrix and high anti-phase boundary energy, strengthen alloys without sacrificing ductility. Such low lattice misfit (0.03 ± 0.04 per cent) decreases the nucleation barrier for precipitation, thus enabling and stabilizing nanoprecipitates with an extremely high number density (more than 1024 per cubic metre) and small size (about 2.7 ± 0.2 nanometres). The minimized elastic misfit strain around the particles does not contribute much to the dislocation interaction, which is typically needed for strength increase. Instead, our strengthening mechanism exploits the chemical ordering effect that creates backstresses (the forces opposing deformation) when precipitates are cut by dislocations. We create a class of steels, strengthened by Ni(Al,Fe) precipitates, with a strength of up to 2.2 gigapascals and good ductility (about 8.2 per cent). The chemical composition of the precipitates enables a substantial reduction in cost compared to conventional maraging steels owing to the replacement of the essential but high-cost alloying elements cobalt and titanium with inexpensive and lightweight aluminium. Strengthening of this class of steel alloy is based on minimal lattice misfit to achieve maximal precipitate dispersion and high cutting stress (the stress required for dislocations to cut through coherent precipitates and thus produce plastic deformation), and we envisage that this lattice misfit design concept may be applied to many other metallic alloys.

Hyperpolarized Xe NMR signal advancement by metal-organic framework entrapment in aqueous solution.

We report hyperpolarized Xe signal advancement by metal-organic framework (MOF) entrapment (Hyper-SAME) in aqueous solution. The 129Xe NMR signal is drastically promoted by entrapping the Xe into the pores of MOFs. The chemical shift of entrapped 129Xe is clearly distinguishable from that of free 129Xe in water, due to the surface and pore environment of MOFs. The influences from the crystal size of MOFs and their concentration in water are studied. A zinc imidazole MOF, zeolitic imidazole framework-8 (ZIF-8), with particle size of 110 nm at a concentration of 100 mg/mL, was used to give an NMR signal with intensity four times that of free 129Xe in water. Additionally, Hyper-SAME is compatible with hyperpolarized 129Xe chemical exchange saturation transfer. The 129Xe NMR signal can be amplified further by combining the two techniques. More importantly, Hyper-SAME provides a way to make detection of hyperpolarized 129Xe in aqueous solution convenient and broadens the application area of MOFs.