Expanded CURB-65: A new score system predicts severity of community-acquired pneumonia with superior efficiency

Aim of this study was to develop a new simpler and more effective severity score for communityacquired pneumonia (CAP) patients. A total of 1640 consecutive hospitalized CAP patients in Second Affiliated Hospital of Zhejiang University were included. The effectiveness of different pneumonia severity scores to predict mortality was compared, and the performance of the new score was validated on an external cohort of 1164 patients with pneumonia admitted to a teaching hospital in Italy. Using age≥ 65 years, LDH>230u/L, albumin<3.5g/dL, platelet count<100×109/L, confusion, urea>7mmol/L, respiratory rate≥30/min, low blood pressure, we assembled a new severity score named as expanded-CURB-65. The 30-day mortality and length of stay were increased along with increased risk score. The AUCs in the prediction of 30-day mortality in the main cohort were 0.826 (95%CI, 0.807–0.844), 0.801 (95%CI, 0.781–0.820), 0.756 (95%CI, 0.735–0.777), 0.793 (95%CI, 0.773–0.813) and 0.759 (95%CI, 0.737–0.779) for the expanded-CURB-65, PSI, CURB-65, SMART-COP and A-DROP, respectively. The performance of this bedside score was confirmed in CAP patients of the validation cohort although calibration was not successful in patients with health care-associated pneumonia (HCAP). The expanded CURB-65 is objective, simpler and more accurate scoring system for evaluation of CAP severity, and the predictive efficiency was better than other score systems

Droplets as Carriers for Flexible Electronic Devices

Coupling soft bodies and dynamic motions with multifunctional flexible electronics is challenging, but is essential in satisfying the urgent and soaring demands of fully soft and comprehensive robotic systems that can perform tasks in spite of rigorous spatial constraints. Here, the mobility and adaptability of liquid droplets with the functionality of flexible electronics, and techniques to use droplets as carriers for flexible devices are combined. The resulting active droplets (ADs) with volumes ranging from 150 to 600 µL can conduct programmable functions, such as sensing, actuation, and energy harvesting defined by the carried flexible devices and move under the excitation of gravitational force or magnetic force. They work in both dry and wet environments, and adapt to the surrounding environment through reversible shape shifting. These ADs can achieve controllable motions at a maximum velocity of 226 cm min−1 on a dry surface and 32 cm min-1 in a liquid environment. The conceptual system may eventually lead to individually addressable ADs that offer sophisticated functions for high-throughput molecule analysis, drug assessment, chemical synthesis, and information collection

Mono-ADP-ribosylation of histone 3 at arginine-117 promotes proliferation through its interaction with P300

Relatively little attention has been paid to ADP-ribosylated modifications of histones, especially to mono-ADP-ribosylation. As an increasing number of mono-ADP-ribosyltransferases have been identified in recent studies, the functions of mono-ADP-ribosylated proteins have aroused research interest. In particular, histones are substrates of some mono-ADP-ribosyltransferases and mono-ADP-ribosylated histone have been detected in physiological or pathological processes. In this research , arginine-117 (Arg-117; R-117) of histone3(H3) is identified as a site of mono-ADP-ribosylation in colon carcinoma(the first such site to be identified); this posttranslational modification may promote the proliferation of colon carcinoma cells in vitro and in vivo. Using a point-mutant lentivirus transfection and using an activator of P300 allowed us to observe the mono-ADP-ribosylation at H3R117 and enhancement of the activity of P300 to up-regulate the level of acetylated β-catenin, which could increase the expression of c-myc and cyclin D1

A Novel Nanobody Specific for Respiratory Surfactant Protein A has Potential for Lung Targeting

Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA) is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA) as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies) specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies\u27 potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high affinity of the nanobody for the lung. Studying acute and chronic toxicity of Nb17 revealed its safety in rats without causing apparent histological alterations. Collectively, we have generated and characterized lung-specific nanobodies, which may be applicable for lung drug delivery

Metatranscriptomic analysis revealed Prevotella as a potential biomarker of oropharyngeal microbiomes in SARS-CoV-2 infection

Background and objectivesDisease severity and prognosis of coronavirus disease 2019 (COVID-19) disease with other viral infections can be affected by the oropharyngeal microbiome. However, limited research had been carried out to uncover how these diseases are differentially affected by the oropharyngeal microbiome of the patient. Here, we aimed to explore the characteristics of the oropharyngeal microbiota of COVID-19 patients and compare them with those of patients with similar symptoms.MethodsCOVID-19 was diagnosed in patients through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Characterization of the oropharyngeal microbiome was performed by metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 144 COVID-19 patients, 100 patients infected with other viruses, and 40 healthy volunteers.ResultsThe oropharyngeal microbiome diversity in patients with SARS-CoV-2 infection was different from that of patients with other infections. Prevotella and Aspergillus could play a role in the differentiation between patients with SARS-CoV-2 infection and patients with other infections. Prevotella could also influence the prognosis of COVID-19 through a mechanism that potentially involved the sphingolipid metabolism regulation pathway.ConclusionThe oropharyngeal microbiome characterization was different between SARS-CoV-2 infection and infections caused by other viruses. Prevotella could act as a biomarker for COVID-19 diagnosis and of host immune response evaluation in SARS-CoV-2 infection. In addition, the cross-talk among Prevotella, SARS-CoV-2, and sphingolipid metabolism pathways could provide a basis for the precise diagnosis, prevention, control, and treatment of COVID-19

Mono-ADP-ribosylation of histone 3 at arginine-117 promotes proliferation through its interaction with P300

Relatively little attention has been paid to ADP-ribosylated modifications of histones, especially to mono-ADP-ribosylation. As an increasing number of mono-ADP-ribosyltransferases have been identified in recent studies, the functions of mono-ADP-ribosylated proteins have aroused research interest. In particular, histones are substrates of some mono-ADP-ribosyltransferases and mono-ADP-ribosylated histone have been detected in physiological or pathological processes. In this research , arginine-117 (Arg-117; R-117) of histone3(H3) is identified as a site of mono-ADP-ribosylation in colon carcinoma(the first such site to be identified); this posttranslational modification may promote the proliferation of colon carcinoma cells in vitro and in vivo. Using a point-mutant lentivirus transfection and using an activator of P300 allowed us to observe the mono-ADP-ribosylation at H3R117 and enhancement of the activity of P300 to up-regulate the level of acetylated β-catenin, which could increase the expression of c-myc and cyclin D1

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation