Superior mechanical properties of multilayer covalent-organic frameworks enabled by rationally tuning molecular interlayer interactions.

Two-dimensional (2D) covalent-organic frameworks (COFs) with a well-defined and tunable periodic porous skeleton are emerging candidates for lightweight and strong 2D polymeric materials. It remains challenging, however, to retain the superior mechanical properties of monolayer COFs in a multilayer stack. Here, we successfully demonstrated a precise layer control in synthesizing atomically thin COFs, enabling a systematic study of layer-dependent mechanical properties of 2D COFs with two different interlayer interactions. It was shown that the methoxy groups in COFTAPB-DMTP provided enhanced interlayer interactions, leading to layer-independent mechanical properties. In sharp contrast, mechanical properties of COFTAPB-PDA decreased significantly as the layer number increased. We attributed these results to higher energy barriers against interlayer sliding due to the presence of interlayer hydrogen bonds and possible mechanical interlocking in COFTAPB-DMTP, as revealed by density functional theory calculations.

Toward Controlled Synthesis of 2D Crystals by CVD: Learning from the Real-Time Crystal Morphology Evolutions.

The rich morphology of 2D materials grown through chemical vapor deposition (CVD), is a distinctive feature. However, understanding the complex growth of 2D crystals under practical CVD conditions remains a challenge due to various intertwined factors. Real-time monitoring is crucial to providing essential data and enabling the use of advanced tools like machine learning for unraveling these complexities. In this study, we present a custom-built miniaturized CVD system capable of observing and recording 2D MoS2 crystal growth in real time. Image processing converts the real-time footage into digital data, and machine learning algorithms (ML) unveil the significant factors influencing growth. The machine learning model successfully predicts CVD growth parameters for synthesizing ultralarge monolayer MoS2 crystals. It also demonstrates the potential to reverse engineer CVD growth parameters by analyzing the as-grown 2D crystal morphology. This interdisciplinary approach can be integrated to enhance our understanding of controlled 2D crystal synthesis through CVD.

Spatially Resolved Anion Diffusion and Tunable Waveguides in Bismuth Halide Perovskites.

Bismuth halide perovskites are widely regarded as nontoxic alternatives to lead halide perovskites for optoelectronics and solar energy harvesting applications. With a tailorable composition and intriguing optical properties, bismuth halide perovskites are also promising candidates for tunable photonic devices. However, robust control of the anion composition in bismuth halide perovskites remains elusive. Here, we established chemical vapor deposition and anion exchange protocols to synthesize bismuth halide perovskite nanoflakes with controlled dimensions and variable compositions. In particular, we demonstrated the gradient bromide distribution by controlling the anion exchange and diffusion processes, which is spatially resolved by time-of-flight secondary ion mass spectrometry. Moreover, the optical waveguiding properties of bismuth halide perovskites can be modulated by flake thicknesses and anion compositions. With a unique gradient anion distribution and controllable optical properties, bismuth halide perovskites provide new possibilities for applications in optoelectronic devices and integrated photonics.

Tuning Local Atomic Structures in MoS2 Based Catalysts for Electrochemical Nitrate Reduction.

In recent years, there has been a substantial surge in the investigation of transition-metal dichalcogenides such as MoS2 as a promising electrochemical catalyst. Inspired by denitrification enzymes such as nitrate reductase and nitrite reductase, the electrochemical nitrate reduction catalyzed by MoS2 with varying local atomic structures is reported. It is demonstrated that the hydrothermally synthesized MoS2 containing sulfur vacancies behaves as promising catalysts for electrochemical denitrification. With copper doping at less than 9% atomic ratio, the selectivity of denitrification to dinitrogen in the products can be effectively improved. X-ray absorption characterizations suggest that two sulfur vacancies are associated with one copper dopant in the MoS2 skeleton. DFT calculation confirms that copper dopants replace three adjacent Mo atoms to form a trigonal defect-enriched region, introducing an exposed Mo reaction center that coordinates with Cu atom to increase N2 selectivity. Apart from the higher activity and selectivity, the Cu-doped MoS2 also demonstrates remarkably improved tolerance toward oxygen poisoning at high oxygen concentration. Finally, Cu-doped MoS2 based catalysts exhibit very low specific energy consumption during the electrochemical denitrification process, paving the way for potential scale-up operations.

Tuning the Surface Electron Accumulation Layer of In2 O3 by Adsorption of Molecular Electron Donors and Acceptors.

In2 O3 , an n-type semiconducting transparent transition metal oxide, possesses a surface electron accumulation layer (SEAL) resulting from downward surface band bending due to the presence of ubiquitous oxygen vacancies. Upon annealing In2 O3 in ultrahigh vacuum or in the presence of oxygen, the SEAL can be enhanced or depleted, as governed by the resulting density of oxygen vacancies at the surface. In this work, an alternative route to tune the SEAL by adsorption of strong molecular electron donors (specifically here ruthenium pentamethylcyclopentadienyl mesitylene dimer, [RuCp*mes]2 ) and acceptors (here 2,2'-(1,3,4,5,7,8-hexafluoro-2,6-naphthalene-diylidene)bis-propanedinitrile, F6 TCNNQ) is demonstrated. Starting from an electron-depleted In2 O3 surface after annealing in oxygen, the deposition of [RuCp*mes]2 restores the accumulation layer as a result of electron transfer from the donor molecules to In2 O3 , as evidenced by the observation of (partially) filled conduction sub-bands near the Fermi level via angle-resolved photoemission spectroscopy, indicating the formation of a 2D electron gas due to the SEAL. In contrast, when F6 TCNNQ is deposited on a surface annealed without oxygen, the electron accumulation layer vanishes and an upward band bending is generated at the In2 O3 surface due to electron depletion by the acceptor molecules. Hence, further opportunities to expand the application of In2 O3 in electronic devices are revealed.

A broadly neutralizing monoclonal antibody induces broad protection against heterogeneous PRRSV strains in piglets.

Neutralizing antibodies (NAbs) have attracted attention as tools for achieving PRRSV control and prevention, but viral antigenic variation undermines the abilities of NAbs elicited by attenuated PRRSV vaccines to confer full protection against heterogeneous PRRSV field isolates. As demonstrated in this study, the monoclonal antibody (mAb) mAb-PN9cx3 exhibited broad-spectrum recognition and neutralizing activities against PRRSV-1 and PRRSV-2 strains in vitro. Furthermore, in vivo experiments revealed that the administration of two 10-mg doses of mAb-PN9cx3 before and after the inoculation of piglets with heterologous PRRSV isolates (HP-PRRSV-JXA1 or PRRSV NADC30-like strain HNhx) resulted in significant reduction of the PRRSV-induced pulmonary pathological changes and virus loads in porcine alveolar macrophages (PAMs) compared with the results obtained with mAb-treated isotype controls. Moreover, minimal hilar lymph node PRRSV antigen levels were observed in mAb-PN9cx3-treated piglets. A transcriptome profile analysis of PAMs extracted from lung tissues of piglets belonging to different groups (except for antibody-isotype controls) indicated that mAb-PN9cx3 treatment reversed the PRRSV infection-induced alterations in expression profiles. A gene ontology (GO) enrichment analysis of these genes traced their functions to pathways that included the immune response, inflammatory response, and response to steroid hormone, and their functions in oogenesis and positive regulation of angiogenesis have been implicated in PRRSV pathogenesis. Overall, NADC30-like HNhx infection affected more gene pathways than HP-PRRSV infection. In conclusion, our research describes a novel immunologic approach involving the use of mAbs that confer cross-protection against serious illness resulting from infection with heterogeneous PRRSV-2 isolates, which is a feat that has not yet been achieved through vaccination. Ultimately, mAb-PN9cx3 will be a powerful addition to our current arsenal for achieving PRRSV prevention and eradication.

Identification of U-shaped curve relation between proneurotensin and risk of coronary artery disease (CAD) in patients with premature CAD.

BACKGROUND AND AIMS: Neurotensin (NT) is a gut hormone with broad effects on the cardiovascular system. Recent data suggested that circulating proneurotensin (pro-NT)-the stable precursor fragment of NT-could independently predict cardiovascular artery disease (CAD) development. However, serum pro-NT levels in patients with premature cardiovascular artery disease (PCAD) are still unknown. This study aims to determine serum pro-NT levels in patients with PCAD and investigate its relationship with PCAD risk. METHODS AND RESULTS: A total of 490 subjects, including 364 with PCAD and 126 without PCAD (NPCAD), and 182 controls were enrolled in the study. Data of baseline clinical parameters and biochemical variables were collected. Serum pro-NT levels were measured by ELISA. Serum pro-NT levels were higher in patients with PCAD than in controls (59.42 ± 66.66 vs. 38.07 ± 48.48 pg/mL, P < 0.05), especially in patients with BMI<25 kg/m2. Serum pro-NT levels were independently related to PCAD (ß = 0.349, P < 0.001), and the association revealed a U-shaped curve characteristic between pro-NT tertiles and CAD risk in patients with premature CAD and controls. Subjects with low and high tertiles of pro-NT levels had 1.79-fold and 2.23-fold higher risks of PCAD, respectively, than subjects with median pro-NT levels (P < 0.05). After adjusting for age, gender, and BMI in Model 1 and other confounders in Model 2 and Model 3, the U-shaped relationship remained significant. CONCLUSION: Serum pro-NT levels were significantly increased in patients with PCAD. The association between pro-NT levels and PCAD risk presents a U-shaped curve characteristic, which demonstrated that subjects with lower and higher pro-NT levels both were more likely to have PCAD.

High serum clusterin levels are associated with premature coronary artery disease in a Chinese population.

BACKGROUND: Clusterin plays an important role in the cardiovascular system, and serum levels of clusterin are higher in coronary artery disease patients. Here, we measured serum clusterin levels in premature coronary artery disease (PCAD) patients and explored the association of these levels with PCAD risk. METHODS: Serum samples and general clinical information were obtained from 672 subjects including 364 PCAD subjects, 126 non-PCAD subjects, and 182 controls. RESULTS: Serum clusterin levels were higher in PCAD patients than in controls, particularly in males with body mass index (BMI) < 25 kg/m2 (P < 0.0001). Compared with the lowest tertile of clusterin, the odds ratio of PCAD in the highest tertile was higher in both a univariate and three adjustment models, and it was 3.146-fold higher in Model 3. This association was especially significant in subgroups with BMI < 25 kg/m2 , total cholesterol < 5.7 mmol/L, high-density lipoprotein cholesterol ≥ 1.0 mmol/L, Urea < 7.14 mmol/L, and estimated glomerular filtration rate < 90 mL/min/1.73 m2 . Serum clusterin may be a potential diagnostic biomarker for PCAD (sensitivity 60.7%, specificity 51.6%, area under the curve 0.595 [95% CI, 0.544-0.647], P < 0.0001), and a combination of clusterin with clinical variables in Model 3 resulted in improved diagnostic accuracy (sensitivity 86.3%, specificity 64.2%, area under the curve 0.829 [95% CI, 0.782-0.877], P < 0.0001). CONCLUSIONS: Serum clusterin levels were increased in PCAD patients, especially for males with BMI < 25 kg/m2 . Higher clusterin levels were independently associated with the presence of PCAD, particularly in subjects with normal BMI, lower total cholesterol, urea, estimated glomerular filtration rate, and higher high-density lipoprotein cholesterol. Clusterin might be a potential diagnostic biomarker for PCAD patients, especially in combination with clinical variables.

Sclerosing Stromal Ovarian Tumor Combined with Early Onset Severe Preeclampsia. A Case Report.

BACKGROUND: Sclerosing stromal tumor (SST) of the ovary is an extremely rare, benign, sex cord-stromal tumor. The tumor consists of cells with the multilineage potential of undifferentiated mesenchymal cells and the ability to secrete estrogen or androgen. Current research suggests that the tumor originates in the ovarian cortex. SSTs of the ovary are predominantly found in young women aged 20-30 years; information describing SST during pregnancy is limited. CASE: We report a case of SST of the ovary combined with early onset severe preeclampsia. CONCLUSION: We document the clinical and pathological characteristics of the patient's disease, including the effects on the pregnancy and fetus.

Spin-Phonon Coupling in Iron-Doped Ultrathin Bismuth Halide Perovskite Derivatives.

Spin in semiconductors facilitates magnetically controlled optoelectronic and spintronic devices. In metal halide perovskites (MHPs), doping magnetic ions is proven to be a simple and efficient approach to introducing a spin magnetic momentum. In this work, we present a facile metal ion doping protocol through the vapor-phase metal halide insertion reaction to the chemical vapor deposition (CVD)-grown ultrathin Cs3BiBr6 perovskites. The Fe-doped bismuth halide (Fe:CBBr) perovskites demonstrate that the iron spins are successfully incorporated into the lattice, as revealed by the spin-phonon coupling below the critical temperature Tc around 50 K observed through temperature-dependent Raman spectroscopy. Furthermore, the phonons exhibit significant softening under an applied magnetic field, possibly originating from magnetostriction and spin exchange interaction. The spin-phonon coupling in Fe:CBBr potentially provides an efficient way to tune the spin and lattice parameters for halide perovskite-based spintronics.

Clinical characteristics and outcomes of immunocompromised patients with severe community-acquired pneumonia: A single-center retrospective cohort study.

Background: Immunocompromised patients with severe community-acquired pneumonia (SCAP) warrant special attention because they comprise a growing proportion of patients and tend to have poor clinical outcomes. The objective of this study was to compare the characteristics and outcomes of immunocompromised and immunocompetent patients with SCAP, and to investigate the risk factors for mortality in these patients. Methods: We conducted retrospective observational cohort study of patients aged ≥18 years admitted to the intensive care unit (ICU) of an academic tertiary hospital with SCAP between January 2017 and December 2019 and compared the clinical characteristics and outcomes of immunocompromised and immunocompetent patients. Results: Among the 393 patients, 119 (30.3%) were immunocompromised. Corticosteroid (51.2%) and immunosuppressive drug (23.5%) therapies were the most common causes. Compared to immunocompetent patients, immunocompromised patients had a higher frequency of polymicrobial infection (56.6 vs. 27.5%, P < 0.001), early mortality (within 7 days) (26.1 vs. 13.1%, P = 0.002), and ICU mortality (49.6 vs. 37.6%, P = 0.027). The pathogen distributions differed between immunocompromised and immunocompetent patients. Among immunocompromised patients, Pneumocystis jirovecii and cytomegalovirus were the most common pathogens. Immunocompromised status (OR: 2.043, 95% CI: 1.114-3.748, P = 0.021) was an independent risk factor for ICU mortality. Independent risk factors for ICU mortality in immunocompromised patients included age ≥ 65 years (odds ratio [OR]: 9.098, 95% confidence interval [CI]: 1.472-56.234, P = 0.018), SOFA score [OR: 1.338, 95% CI: 1.048-1.708, P = 0.019), lymphocyte count < 0.8 × 109/L (OR: 6.640, 95% CI: 1.463-30.141, P = 0.014), D-dimer level (OR: 1.160, 95% CI: 1.013-1.329, P = 0.032), FiO2 > 0.7 (OR: 10.228, 95% CI: 1.992-52.531, P = 0.005), and lactate level (OR: 4.849, 95% CI: 1.701-13.825, P = 0.003). Conclusions: Immunocompromised patients with SCAP have distinct clinical characteristics and risk factors that should be considered in their clinical evaluation and management.

Clinical characteristics and prognosis of pneumonia-related bloodstream infections in the intensive care unit: a single-center retrospective study.

Background: Bloodstream infections (BSI) are one of the most severe healthcare-associated infections in intensive care units (ICU). However, there are few studies on pneumonia-related BSI (PRBSI) in the ICU. This study aimed to investigate the clinical and prognostic characteristics of patients with PRBSI in the ICU and to provide a clinical basis for early clinical identification. Methods: We retrospectively collected data from patients with bacterial BSI in a single-center ICU between January 1, 2017, and August 31, 2020. Clinical diagnosis combined with whole-genome sequencing (WGS) was used to clarify the diagnosis of PRBSI, and patients with PRBSI and non-PRBSI were analyzed for clinical features, prognosis, imaging presentation, and distribution of pathogenic microorganisms. Results: Of the 2,240 patients admitted to the MICU, 120 with bacterial BSI were included in this study. Thirty-two (26.7%) patients were identified as having PRBSI based on the clinical diagnosis combined with WGS. Compared to patients without PRBSI, those with PRBSI had higher 28-day mortality (81.3 vs.51.1%, p = 0.003), a higher total mortality rate (93.8 vs. 64.8%, p = 0.002), longer duration of invasive mechanical ventilation (median 16 vs. 6 days, p = 0.037), and prolonged duration of ICU stay (median 21 vs. 10 days, p = 0.004). There were no differences in other baseline data between the two groups, but patients with PRBSI had extensive consolidation on chest radiographs and significantly higher Radiographic Assessment of Lung Edema scores (mean 35 vs. 24, p < 0.001). The most common causative organisms isolated in the PRBSI group were gram-negative bacteria (n = 31, 96.9%), with carbapenem-resistant gram-negative bacteria accounting for 68.8% (n = 22) and multidrug-resistant bacteria accounting for 81.3% (n = 26). Conclusion: Pneumonia-related BSI is an important component of ICU-BSI and has a poor prognosis. Compared to non-PRBSI, patients with PRBSI do not have typical clinical features but have more severe lung consolidation lesions, and should be alerted to the possibility of their occurrence when combined with pulmonary gram-negative bacterial infections, especially carbapenem-resistant bacteria. Further multicenter, large-sample studies are needed to identify the risk factors for the development of PRBSI and prevention and treatment strategies.

Identification of avian polyomavirus and its pathogenicity to SPF chickens.

The research aimed to study an Avian polyomavirus strain that was isolated in Shandong, China. To study the pathogenicity of APV in SPF chickens, and provide references for epidemiological research and disease prevention and control of APV. The genetic characterization of APV strain (termed APV-20) was analyzed and the pathogenicity of APV was investigated from two aspects: different age SPF chickens, and different infection doses. The results revealed that the APV-20 exhibits a nucleotide homology of 99% with the other three APV strains, and the evolution of APV In China was slow. In addition, the APV-20 infection in chickens caused depression, drowsiness, clustering, and fluffy feathers, but no deaths occurred in the infected chickens. The main manifestations of necropsy, and Hematoxylin and Eosin staining (HE) showed that one-day-old SPF chickens were the most susceptible, and there was a positive correlation between viral load and infection dose in the same tissue. This study showed that SPF chickens were susceptible to APV, and an experimental animal model was established. This study can provide a reference for the pathogenic mechanism of immune prevention and control of APV.

Prognostic Value of Syndecan-1 in the Prediction of Sepsis-Related Complications and Mortality: A Meta-Analysis.

Aim: Syndecan-1 (SDC-1) has been shown to have a high predictive value for sepsis development, though uncertainty around these results exists. The aim of this meta-analysis was to assess the prognostic ability of SDC-1 in predicting sepsis-related complications and mortality. Methods: We searched PubMed, EMBASE, Cochrane Library, and Google Scholar databases from January 01, 1990, to March 17, 2021, to identify eligible studies. The search terms used were "SDC-1," "sepsis," "severe sepsis," and "septic shock," and a meta-analysis was performed using the RevMan 5.4 software. Results: Eleven studies with a total of 2,318 enrolled patients were included. SDC-1 concentrations were significantly higher in the composite poor outcome group [standardized mean difference (SMD) = 0.55; 95% CI: 0.38-0.72; P < 0.001] as well as in deceased patients (SMD = 0.53; 95% CI: 0.40-0.67; P < 0.001), patients with septic shock (SMD = 0.81; 95% CI: 0.36-1.25; P < 0.001), and patients with acute kidney injury (SMD = 0.48; 95% CI: 0.33-0.62; P < 0.001). Statistical significance was also found in the subgroup analysis when stratified by different sepsis diagnostic criteria. Conclusion: Baseline SDC-1 levels may be a useful predictor of sepsis-related complications and mortality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246344, PROSPERO, identifier: CRD42021246344.

Risk factors for intracranial hemorrhage and mortality in adult patients with severe respiratory failure managed using veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Intracerebral hemorrhage (ICH) is one of the most severe complications during veno-venous extracorporeal membrane oxygenation (VV-ECMO). This study aimed to determine the risk factors for ICH and mortality in such patients. METHODS: We analyzed the clinical data of 77 patients who received VV-ECMO due to severe respiratory failure from July 2013 to May 2019 at China-Japan Friendship Hospital. Demographical data, laboratory indices, imaging characteristics, and other clinical information were collected. Multivariable logistic regression analyses were performed to identify risk factors for ICH and mortality. RESULTS: Of 77 patients, 11 (14.3%) suffered from ICH, and 36 (46.8%) survived. The survival rate was significantly lower (18.2% [2/11] vs. 51.5% [34/66], P = 0.040) in patients with ICH than in those without ICH. Multivariable analysis revealed that factors independently associated with ICH were diabetes mellitus (adjusted odds ratio [aOR]: 12.848, 95% confidence interval [CI]: 1.129-146.188, P = 0.040) and minimum fibrinogen during ECMO (aOR: 2.557, 95% CI: 1.244-5.252, P = 0.011). Multivariable analysis showed that factors independently associated with mortality were acute hepatic failure during ECMO (aOR: 9.205, 95% CI: 1.375-61.604, P = 0.022), CO2 retention before ECMO (aOR: 7.602, 95% CI: 1.514-38.188, P = 0.014), and minimum platelet concentration during ECMO (aOR: 0.130, 95% CI: 0.029-0.577, P = 0.007). CONCLUSIONS: Diabetes mellitus and minimum fibrinogen concentration during ECMO are risk factors for ICH in patients with severe respiratory failure managed using VV-ECMO. This indicated that anticoagulants use and nervous system monitoring should be performed more carefully in patients with diabetes when treated with VV-ECMO due to severe respiratory failure.

A Paired Comparison of Plasma and Bronchoalveolar Lavage Fluid for Metagenomic Next-Generation Sequencing in Critically Ill Patients with Suspected Severe Pneumonia.

Purpose: Plasma metagenomic next-generation sequencing (mNGS) has emerged as an attractive and minimally invasive technique for pathogen detection. However, few studies have demonstrated the need for simultaneous plasma and bronchoalveolar lavage fluid (BALF) mNGS in patients with severe pneumonia. Patients and Methods: This study retrospectively performed a paired comparison of BALF and plasma mNGS in critically ill patients with suspected severe pneumonia from April 2019 to December 2020. The diagnostic performance of BALF and plasma mNGS was compared using the clinical composite diagnosis as the reference standard. Results: In total, 57 patients were included in this study. Patients with positive plasma mNGS had shorter hospital stay days at the time of specimen acquisition (4.5 vs 11, P = 0.028) and a higher positivity rate of BALF culture (50% vs 22.9%, P = 0.033) than patients with negative plasma mNGS. Fifty-three patients (93%) were finally diagnosed with severe pneumonia. Significant differences were observed in the sensitivity of BALF and plasma mNGS (100% vs 42%, P < 0.001), and the diagnostic accuracy was 96% and 46%, respectively. The proportion of virus in positive plasma mNGS results was higher than that in BALF mNGS (23% vs 11%, P = 0.173) without significant difference. Although plasma mNGS detected additional microorganisms in 11/53 patients, the beneficial effect was observed in only 5/53 (9%) patients. Conclusion: In this study, the clinical effect of simultaneously conducting mNGS of BALF and plasma samples was found to be limited. For patients with the suspected virus infection, plasma mNGS may be a supplementary test. Further studies are needed to identify the optimal indications for plasma mNGS.

Mucus-permeable polymyxin B-hyaluronic acid/ poly (lactic-co-glycolic acid) nanoparticle platform for the nebulized treatment of lung infections.

The aim of this study was to improve the bioavailability of polymyxin B (PMB) in pulmonary nebulized drug delivery. To this end, we developed a nano-delivery system that penetrates the mucus barrier of the lung. Hydrophilic hyaluronic acid (HA) was combined with a water-in-oil system containing a poly (lactic acid)-glycolic acid copolymer of PMB to prepare HA@PLGA-PMB nanoparticles (NPs) with good surface properties. HA@PLGA-PMB NPs with suitable electrical properties, particle size, and good hydrophilicity prevented strong interactions between the NPs and mucus, thereby allowing more drugs to enter deeper into the lung. Compared to the free drug PMB, NPs had more than 2-fold higher mucus penetration efficiency in vitro and better delivery to infected alveolar cells during in vivo nebulization. NPs had better biocompatibility, which further reduced the drug toxicity. More importantly, NPs showed better antimicrobial therapeutic efficacy in the treatment of lung infections in mice. These findings may provide support for the clinical application of nebulized pulmonary antibiotics.

An inflammation-targeted nanoparticle with bacteria forced release of polymyxin B for pneumonia therapy.

The epidemic of multidrug-resistant Gram-negative bacteria is an ever-growing global concern. Polymyxin B (PMB), a kind of "old fashioned" antibiotic, has been revived in clinical practice and mainly used as last-line antibiotics for otherwise untreatable serious infections because the incidence of the resistance to PMB is currently relatively low in comparison with other antibiotics in vivo owing to the unique bactericidal mechanism of PMB. However, serious adverse side effects, including nephrotoxicity and neurotoxicity, hamper its clinical application. Herein, we describe the development of a nanoparticle that can target sites of inflammation and forcedly release PMB specifically in the area of Gram-negative bacteria. This particle was constructed through the electrostatic self-assembly of hyaluronic acid (HA) and PMB molecules in order to realize the safe and effective treatment of pneumonia. After systemic administration, PMB-HA nanoparticles were found to actively accumulate in the lungs, precisely target the CD44 receptors over-expressed on the membrane of activated endothelial cells in inflammatory sites, and then come into contact with the bacteria resident in the damaged alveolar-capillary membrane. Due to the electrostatic and hydrophobic interactions between PMB and the lipopolysaccharide (LPS) in the outer membranes of bacteria, the PMB molecules in the PMB-HA nanoparticles are expected to escape from the nanoparticles to insert into the bacteria via competitive binding with LPS. Through shielding the cationic nature of PMB, PMB-HA nanoparticles also possess outstanding biosafety performance in comparison to free PMB. It is thus believed that this smart delivery system may pave a new way for the resurrection of PMB in the future clinical treatment of bacterial inflammatory diseases.

Ultrahigh resistance of hexagonal boron nitride to mineral scale formation.

Formation of mineral scale on a material surface has profound impact on a wide range of natural processes as well as industrial applications. However, how specific material surface characteristics affect the mineral-surface interactions and subsequent mineral scale formation is not well understood. Here we report the superior resistance of hexagonal boron nitride (hBN) to mineral scale formation compared to not only common metal and polymer surfaces but also the highly scaling-resistant graphene, making hBN possibly the most scaling resistant material reported to date. Experimental and simulation results reveal that this ultrahigh scaling-resistance is attributed to the combination of hBN's atomically-smooth surface, in-plane atomic energy corrugation due to the polar boron-nitrogen bond, and the close match between its interatomic spacing and the size of water molecules. The latter two properties lead to strong polar interactions with water and hence the formation of a dense hydration layer, which strongly hinders the approach of mineral ions and crystals, decreasing both surface heterogeneous nucleation and crystal attachment.

Metagenomic Next-Generation Sequencing for Pathogenic Diagnosis and Antibiotic Management of Severe Community-Acquired Pneumonia in Immunocompromised Adults.

Background: Metagenomic next-generation sequencing (mNGS) is a promising technique for pathogens diagnosis. However, application of mNGS in immunocompromised adults with severe community-acquired pneumonia (SCAP) is relatively limited. Methods: We retrospectively reviewed 23 immunocompromised and 21 immunocompetent SCAP patients with mNGS detection from April 2019 to December 2019. The performances of pathogenic diagnosis and subsequently antibiotic adjustment in immunocompromised SCAP patients were compared to immunocompetent SCAP patients. The defined by days of therapy (DOT) method was used for estimate daily antibiotic use. Results: There was a significant difference in the diagnostic positivity rate between mNGS and conventional test in both groups (P<0.001). Compared to immunocompetent patients, more mixed pathogens in immunocompromised patients were found (P=0.023). Before the availability of mNGS, the DOTs in immunocompromise patients were higher than immunocompetent patients (3.0 [3.0, 4.0] vs. 3.0 [2.0, 3.0], P=0.013). Compared to immunocompetent patients, immunocompromised patients had fewer full pathogen covered empirical antibiotic therapy (14.7% vs. 57.1%, P=0.022), more adjustments of antibiotic treatment (87.0%) vs. 57.1%, P=0.027). More than a half (13 of 23) SCAP patients in immunosuppressed group had reduced or downgraded antibiotic adjustments based on the results. Conclusions: mNGS may be a useful technique for detecting mixed pathogens and personalized antibiotic treatment in immunocompromised SCAP patients.