PepPre: Promote Peptide Identification Using Accurate and Comprehensive Precursors.

Accurate and comprehensive peptide precursor ions are crucial to tandem mass-spectrometry-based peptide identification. An identification engine can derive great advantages from the search space reduction enabled by credible and detailed precursors. Furthermore, by considering multiple precursors per spectrum, both the number of identifications and the spectrum explainability can be substantially improved. Here, we introduce PepPre, which detects precursors by decomposing peaks into multiple isotope clusters using linear programming methods. The detected precursors are scored and ranked, and the high-scoring ones are used for subsequent peptide identification. PepPre is evaluated both on regular and cross-linked peptide data sets and compared with 11 methods. The experimental results show that PepPre achieves a remarkable increase of 203% in PSM and 68% in peptide identifications compared to instrument software for regular peptides and 99% in PSM and 27% in peptide pair identifications for cross-linked peptides, surpassing the performance of all other evaluated methods. In addition to the increased identification numbers, further credibility evaluations evidence the reliability of the identified results. Moreover, by widening the isolation window of data acquisition from 2 to 8 Th, with PepPre, an engine is able to identify at least 64% more PSMs, thereby demonstrating the potential advantages of wide-window data acquisition. PepPre is open-source and available at http://peppre.ctarn.io.

Highly Stretchable, Knittable, Wearable Fiberform Hydrovoltaic Generators Driven by Water Transpiration for Portable Self-Power Supply and Self-Powered Strain Sensor.

The development of excellently stretchable, highly mobile, and sustainable power supplies is of great importance for self-power wearable electronics. Transpiration-driven hydrovoltaic power generator (HPG) has been demonstrated to be a promising energy harvesting strategy with the advantages of negative heat and zero-carbon emissions. Herein, this work demonstrates a fiber-based stretchable HPG with the advantages of high output, portability, knittability, and sustainable power generation. Based on the functionalized micro-nano water diffusion channels constructed by the discarded mask straps (MSs) and oxidation-treated carbon nanomaterials, the applied water can continuously produce electricity during the spontaneous flow and diffusion. Experimentally, when a tiny 0.1 mL of water encounters one end of the proposed HPG, the centimeter-length device can yield a peak voltage of 0.43 V, peak current of 29.5 µA, and energy density of 5.833 mW h cm-3. By efficiently integrating multiple power generation units, sufficient output power can be provided to drive commercial electronic devices even in the stretched state. Furthermore, due to the reversibility of the electrical output during dynamic stretching-releasing, it can passively convert physiological activities and motion behaviors into quantifiable and processable current signals, opening up HPG's application in the field of self-powered wearable sensing.

Real-world effectiveness of nirmatrelvir-ritonavir versus azvudine in hospitalized patients with COVID-19 during the omicron wave in Beijing: a multicenter retrospective cohort study.

BACKGROUND AND AIM: Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. METHODS: This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. RESULTS: After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1-3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6-4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80-1.86, P = 0.43). CONCLUSION: Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment.

Single-cell landscape of immunological responses in elderly patients with sepsis.

Sepsis is a dysregulated host response to severe infections, and immune dysfunction plays a crucial role in its pathogenesis. Elderly patients, a special population influenced by immunosenescence, are more susceptible to sepsis and have a worse prognosis. However, the immunopathogenic mechanisms underlying sepsis in elderly patients remain unclear. Here, we performed single-cell RNA sequencing of peripheral blood samples from young and old subjects and patients with sepsis. By exploring the transcriptional profiles of immune cells, we analyzed immune cell compositions, phenotype shifts, expression heterogeneities, and intercellular communication. In elderly patients with sepsis, innate immune cells (e.g., monocytes and DCs) exhibit decreased antigen presentation, presenting an overactive inflammatory and senescent phenotype. However, the immunophenotype of T cells shifted to characterize effector, memory, and exhaustion. Moreover, we identified strong interferon-γ responses of T cells in both aging and sepsis groups and a deranged inflammaging status in elderly sepsis patients. Tregs in elderly patients with sepsis showed increased abundance and enhanced immunosuppressive effects. In addition, metabolism-associated pathways were upregulated in T cells in elderly patients with sepsis, and the lysine metabolism pathway was enriched in Tregs. Cell-cell interaction analysis showed that the expression profile of ligand-receptor pairs was probably associated with aggravated immune dysfunction in elderly patients with sepsis. A novel HLA-KIR interaction was observed between Tregs and CD8 + T cells. These findings illustrate the immunological hallmarks of sepsis in elderly patients, and highlight that immunosuppressive and metabolic regulatory pathways may undergo important alterations in elderly patients with sepsis.

Protein conformation characterization via a silicon resonator-based optical sensor based on the combination of wavelength interrogation and dual polarization detection.

Protein conformational abnormality causes cell malfunction. Conformational change of amyloid protein causes neuron malfunction, which renders "protein conformational disease" Alzheimer's disease. Dual polarization interferometry enables to provide one-dimensional structure of a protein biolayer via deconvolution of interference patterns, which in turn is interpreted as the protein molecule conformation. However, it is still challenging to avoid interference patterns becoming faint and obscure sometimes. Resonance wavelength response to the biolayer structure can achieve a very low detection limit due to inherent high Q factor of an optical resonator. Here, we introduce the concept of combining dual polarization detection with wavelength interrogation via a simple and compact resonator-based optical biosensor. Biolayer were probed by the wave of dual polarization and its opto-geometrical parameters were resolved into resonance wavelength shift. Because protein molecule with distinct conformation produced a biolayer with unique thickness and mass density. Amyloid proteins in monomeric and dimeric morphology were respectively characterized. This concept enables protein conformation characterization in an easy and direct paradigm and provides a desirable sensing performance due to sensitive resonance response in the form of the sharp resonance profile occurring in a nonoverlapping spectrum.

TREM-1 promoted apoptosis and inhibited autophagy in LPS-treated HK-2 cells through the NF-κB pathway.

Triggering receptor expressed by myeloid cells (TREM-1) is an amplifier of inflammatory responses triggered by bacterial or fungal infection. Soluble TREM-1 (sTREM-1) expression was found to be upregulated in sepsis-associated acute kidney injury (SA-AKI) and predicted to be a potential biomarker. However, the mechanism remains unclear. The human kidney-2 (HK-2) cell line was treated with lipopolysaccharide (LPS) and used to examine the potential roles of TREM-1 in apoptosis and autophagy. A cell viability assay was employed to assess the number of viable cells and as a measure of the proliferative index. The concentrations of sTREM-1, interleukin (IL)-1ß, tumor necrosis factor-α (TNFα) and IL-6 in cell-free culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to analyze apoptosis, autophagy and the relevant signaling pathways. The results suggested that TREM-1 overexpression after LPS treatment decreased proliferation and increased apoptosis. The concentrations of sTREM-1, IL-1ß, TNFα and IL-6 in cell-free culture supernatants were increased in the TREM-1 overexpression group after LPS treatment. Expression of the antiapoptotic gene Bcl-2 was downregulated in the TREM-1 overexpression group, while that of the proapoptotic genes Bax, cleaved caspase-3 and cleaved caspase-9 was upregulated. Overexpression of TREM-1 downregulated expression of the autophagy genes Beclin-1, Atg-5 and LC3b and increased the gene expression of p62, which inhibits autophagy. Conversely, treatment with TREM-1-specific shRNA had the opposite effects. The nuclear factor-κB (NF-κB) signaling pathway (P-p65/p65 and P-IκBα/IκBα) in LPS-induced HK-2 cells was regulated by TREM-1. In summary, TREM-1 promoted apoptosis and inhibited autophagy in HK-2 cells in the context of LPS exposure potentially through the NF-κB pathway.

GameTag: A New Sequence Tag Generation Algorithm Based on Cooperative Game Theory.

Sequence tag-based peptide search is a critical technology in proteomics for the characterization of proteins from tandem mass spectrometry data. However, the main reason for hindering the full application of such an approach lies that accurately extracting sequence tags responsible for each experimental spectrum. Toward that end, GameTag, a novel cooperative game framework for sequence tag generation is proposed, which includes a tag generator and a tag discriminator to collaboratively generate sequence tags. Specifically, the tag generator works to extract as many correct tag candidates as possible and the tag discriminator serves to determine the correctness of tag candidates and reduce the total number of output tags simultaneously. Through the dynamic two-player game, the number of extracted tags is decreased while the number of correct tags gets boosted. The performance of the proposed method is also investigated under various hyperparameter and structure settings. Extensive experiments on a wide variety of data sets from different species demonstrate that GameTag outperforms previous state-of-the-art methods, InsPecT, PepNovo+, DirecTag, and the existing tag-extraction method in Open-pFind, increasing by at least 10% the number of spectra extracted more than one correct tag.

Diagnostic value of Candida mannan antigen and anti-mannan IgG and IgM antibodies for Candida infection.

OBJECTIVE: To assess the diagnostic value of serum Candida mannan antigen (MN) and anti-mannan IgG and IgM antibodies for candidiasis. METHODS: This study was a prospective cohort study. Clinical data and venous blood samples from 23 medical centres in Beijing, China were collected between 1 January 2017 and 31 December 2018. All collected specimens were tested within one week for serum Candida MN and IgG and IgM antibodies using an ELISA kit. RESULTS: A total of 452 patients were enrolled, including 188 patients in the Candida exposure groups (56 patients with Candida bloodstream infection, 69 patients with Candida-positive tracheal aspirate cultures and 63 patients with Candida-positive urine cultures) and 264 patients in the control groups (212 healthy controls and 52 patients with bacteraemia). The receiver operating characteristic (ROC) curve of the 56 patients with Candida bloodstream infection and 212 healthy controls showed that serum MN and IgG had good diagnostic value. The area under the ROC curve (AUC) values were 0.812 (95% CI, 0.750-0.873) and 0.866 (95% CI, 0.808-0.924), respectively, wherein the MN specificity and sensitivity were 86.79% and 60.71%, and the IgG were 84.43% and 80.36%, respectively. The AUC of the combination of serum MN and IgG was 0.871(95% CI, 0.813-0.929), and the specificity and sensitivity were 93.87% and 57.14%. CONCLUSIONS: The serum levels of Candida MN and its IgG antibody have diagnostic value for Candida bloodstream infection, and combination of MN and IgG can improve diagnostic specificity and may provide a new approach for diagnosis of candidaemia.

Prospective study of the serum Aspergillus-specific IgG, IgA and IgM assays for chronic pulmonary aspergillosis diagnosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA. METHODS: The prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit. RESULTS: A total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5µg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively. CONCLUSIONS: The sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis. TRIAL REGISTRATION: NCT03027089 . Registered 20 January 2017.

SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGFß-mediated epithelial to mesenchymal transition in human lung cancer cell line A549.

A post-transcriptional pathway by which TGF-ß modulates expression of specific proteins, Disabled-2 (Dab2) and Interleukin-like EMT Inducer (ILEI), inherent to epithelial to mesenchymal transition (EMT) in murine epithelial cells through Akt2-mediated phosphorylation of poly r(C) binding protein (PCBP1), has been previously elucidated. The aims of the current study were to determine if the same mechanism is operative in the non-small cell lung cancer (NSCLC) cell line, A549, and to delineate the underlying mechanism. Steady-state transcript and protein expression levels of Dab2 and ILEI were examined in A549 cells treated with TGF-ß for up to 48 h. Induction of translational de-repression in this model was quantified by polysomal fractionation followed by qRT-PCR. The underlying mechanism of isoform-specific activation of Akt2 was elucidated through a combination of co-immunoprecipitation studies. TGF-ß induced EMT in A549 cells concomitant with translational upregulation of Dab2 and ILEI proteins through isoform-specific activation of Akt2 followed by phosphorylation of PCBP1 at serine-43. Our experiments further elucidated that the adaptor protein SchA is phosphorylated at tyrosine residues following TGF-ß treatment, which initiated a signaling cascade resulting in the sequential recruitment of p85 subunit of PI3K and focal adhesion kinase (FAK). The SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1. Inhibition of the p85 subunit through phosphorylated 1257 peptide completely attenuated EMT in these cells. We have defined the underlying mechanism responsible for isoform-specific recruitment and activation of Akt2, not Akt1, during TGF-ß-mediated EMT in A549 cells. Inhibition of the formation of this complex thus represents an important and novel therapeutic target in metastatic lung carcinoma.

Research of biomimetic corrugation on the blade flutter suppression in large-scale wind turbine systems.

Aiming at the blade flutter of large horizontal-axis wind turbines, a method by utilizing biomimetic corrugation to suppress blade flutter is first proposed. By extracting the dragonfly wing corrugation, the biomimetic corrugation airfoil is constructed, finding that mapping corrugation to the airfoil pressure side has better aerodynamic performance. The influence of corrugation type, amplitudeλ, and intensity on airfoil flutter is analyzed using orthogonal experiment, which determines that theλhas the greatest influence on airfoil flutter. Based on the fluctuation range of the moment coefficient ΔCm, the optimal airfoil flutter suppression effect is obtained when the type is III,λ= 0.6, and intensity is denser (n= 13). The effective corrugation layout area in the chord direction is determined to be the leading edge, and the ΔCmof corrugation airfoil is reduced by 7.405%, compared to the original airfoil. The application of this corrugation to NREL 15 MW wind turbine 3D blades is studied, and the influence of corrugation layout length in the blade span direction on the suppressive effect is analyzed by fluid-structure interaction. It is found that when the layout length is 0.85 R, the safety marginSfreaches a maximum value of 0.3431 Hz, which is increased 2.940%. The results show that the biomimetic corrugated structure proposed in this paper can not only improve the aerodynamic performance by changing the local flow field on the surface of the blade, but also increase the structural stiffness of the blade itself, and achieve the effect of flutter suppression.

A Clinical Bacterial Dataset for Deep Learning in Microbiological Rapid On-Site Evaluation.

Microbiological Rapid On-Site Evaluation (M-ROSE) is based on smear staining and microscopic observation, providing critical references for the diagnosis and treatment of pulmonary infectious disease. Automatic identification of pathogens is the key to improving the quality and speed of M-ROSE. Recent advancements in deep learning have yielded numerous identification algorithms and datasets. However, most studies focus on artificially cultured bacteria and lack clinical data and algorithms. Therefore, we collected Gram-stained bacteria images from lower respiratory tract specimens of patients with lung infections in Chinese PLA General Hospital obtained by M-ROSE from 2018 to 2022 and desensitized images to produce 1705 images (4,912 × 3,684 pixels). A total of 4,833 cocci and 6,991 bacilli were manually labelled and differentiated into negative and positive. In addition, we applied the detection and segmentation networks for benchmark testing. Data and benchmark algorithms we provided that may benefit the study of automated bacterial identification in clinical specimens.

Associations of nirmatrelvir-ritonavir treatment with death and clinical improvement in hospitalized patients with COVID-19 during the Omicron wave in Beijing, China: a multicentre, retrospective cohort study.

BACKGROUND: The effectiveness of nirmatrelvir-ritonavir has mainly been shown in non-hospitalized patients with mild-to-moderate coronavirus disease 2019 (COVID-19). The real-world effectiveness of nirmatrelvir-ritonavir urgently needs to be determined using representative in-hospital patients with COVID-19 during the Omicron wave of the pandemic. METHODS: We performed a multicentre, retrospective study in five Chinese PLA General Hospital medical centers in Beijing, China. Patients hospitalized with COVID-19 from 10 December 2022 to 20 February 2023 were eligible for inclusion. A 1:1 propensity score matching was performed between the nirmatrelvir-ritonavir group and the control group. RESULTS: 1010 recipients of nirmatrelvir-ritonavir and 1010 matched controls were finally analyzed after matching. Compared with matched controls, the nirmatrelvir-ritonavir group had a lower incidence rate of all-cause death (4.6/1000 vs. 6.3/1000 person-days, p = 0.013) and a higher incidence rate of clinical improvement (47.6/1000 vs. 45.8/1000 person-days, p = 0.012). Nirmatrelvir-ritonavir was associated with a 22% lower all-cause mortality and a 14% higher incidence of clinical improvement. Initiation of nirmatrelvir-ritonavir within 5 days after symptom onset was associated with a 50% lower mortality and a 26% higher clinical improvement rate. By contrast, no significant associations were identified among patients receiving nirmatrelvir-ritonavir treatment more than 5 days after symptom onset. Nirmatrelvir-ritonavir was also associated with a 50% increase in survival days and a 12% decrease in days to clinical improvement. CONCLUSION: Among hospitalized patients with COVID-19 during the Omicron wave in Beijing, China, the early initiation of nirmatrelvir-ritonavir was associated with clinical benefits of lowering mortality and improving clinical recovery.

Rapid detection of Salmonella in food matrices by photonic PCR based on the photothermal effect of Fe3O4.

Salmonella causes most deaths from diarrheal disease worldwide. Therefore, Salmonella must be accurately and quickly detected, even in complex food matrices, which is difficult to achieve using conventional culture methods. Here we propose a novel photonic polymerase chain reaction (PCR) method based on ferroferric oxide (Fe3O4) for the detection of Salmonella typhimurium in complex samples. Owing to the great photothermal conversion performance of Fe3O4, rapid thermal cycling could be accomplished. Our optimized photonic PCR system specifically detected Salmonella typhimurium in complex food matrices within 50 min. Quantitative data showed a limit of detection up to 102 CFU/mL in food samples. This method is suitable for the detection of all pathogenic microorganisms and is universal.

Metformin enhances T lymphocyte anti-tumor immunity by increasing the infiltration via vessel normalization.

Abnormal tumor vasculature blocks the extravasation of T lymphocytes into the tumor, thereby suppressing anti-tumor immunity. Recently, metformin has been shown to affect tumor vasculature and enhance T lymphocyte anti-tumor immunity. However, whether or how metformin affects T lymphocyte anti-tumor immunity via a vascular mechanism remains poorly understood. Herein, we show that a large number of CD8+ lymphocytes gathered in the peri-tumoral region, while very few infiltrated the tumor. Metformin administration increased the expression of anti-tumor immunity-associated genes and the number of tumor-infiltrating CD8+ lymphocytes. Injection of CD8 but not CD4 neutralization antibody into tumor-bearing mice significantly abrogated the anti-tumor effect of metformin. Critically, CD8+ lymphocytes were found to pass through the wall of perfused vessel. Further results of immunofluorescent staining showed that metformin greatly elevated tumor perfusion, which was accompanied by increased vascular maturity in the intratumoral region (ITR) but not peritumoral region (PTR). These findings provide evidence for the vascular mechanism involved in metformin-induced enhancement of T lymphocyte anti-tumor immunity. By remodeling the abnormal tumor vasculature, also called vessel normalization metformin increases vascular maturity and tumor perfusion, thus allowing more CD8+ lymphocytes to infiltrate the tumor.

Severe Community-Acquired Pneumonia Caused by Methicillin-Sensitive Staphylococcus aureus: Successfully Treated with Contezolid - A Case Report and Literature Review.

Background: Staphylococcus aureus has been well recognized as an important cause of community-acquired pneumonia (CAP), with non-specific characteristics and poor prognosis. In severe CAP (SCAP) guidelines, ß-lactam combined with macrolides or fluoroquinolones therapy was recommended, but the efficacy is not satisfactory due to the continued spread of antimicrobial resistance. Contezolid is a new representative of oxazolidinones in clinical development, but no relevant reports have been reported for the treatment of SCAP. This was the first report of a patient with Staphylococcus aureus SCAP who was successfully treated with contezolid combined with other antibiotics and rehabilitation exercise. Case Presentation: A 44-year-old woman with high blood pressure and diabetes was admitted to our hospital owing to cough, sputum, wheezing for 2 weeks, and aggravation for 2 days. The bronchoscopic alveolar lavage and microorganism-Rapid On Site Evaluation (BAL-mROSE) was used to get pathological data, which were positive for Staphylococcus aureus, in line with blood cultures. During hospitalization, the patient received endotracheal intubation for assisted breathing and anti-infective therapy, including meropenem, linezolid, teicoplanin and tazocin successively. Finally, contezolid obtained excellent result, with platelet recovery to normal levels and significant improvement in pulmonary imaging. Meanwhile, the patient's swallowing disorder improved after continuous rehabilitation exercise. After discharge, she received contezolid consolidation therapy for 1 week and was free of complaints during the 30-day follow-up without any special treatment for SCAP. Discussion: Treatment with contezolid combined with other antibiotics and rehabilitation exercise for SCAP has shown remarkable efficacy and good safety; hence, this regimen is a promising treatment strategy for this fatal disease.

Highly sensitive piezoresistive and thermally responsive fibrous networks from the in situ growth of PEDOT on MWCNT-decorated electrospun PU fibers for pressure and temperature sensing.

Flexible electronics have demonstrated various strategies to enhance the sensory ability for tactile perception and wearable physiological monitoring. Fibrous microstructures have attracted much interest because of their excellent mechanical properties and fabricability. Herein, a structurally robust fibrous mat was first fabricated by electrospinning, followed by a sequential process of functionalization utilizing ultrasonication treatment and in situ polymerization growth. Electrospun polyurethane (PU) microfibers were anchored with multi-walled carbon nanotubes (MWCNTs) to form conductive paths along each fiber by a scalable ultrasonic cavitation treatment in an MWCNT suspension. After, a layer of poly(3,4-ethylene dioxythiophene) (PEDOT) was grown on the surface of PU fibers decorated with MWCNTs to enhance the conductive conjunctions of MWCNTs. Due to the superior electromechanical behaviors and mechanical reinforcement of PEDOT, the PEDOT/MWCNT@PU mat-based device exhibits a wide working range (0-70 kPa), high sensitivity (1.6 kPa-1), and good mechanical robustness (over 18,000 cycles). The PEDOT/MWCNT@PU mat-based sensor also demonstrates a good linear response to different temperature variations because of the thermoelectricity of the PEDOT/MWCNT composite. This novel strategy for the fabrication of multifunctional fibrous mats provides a promising opportunity for future applications for high-performance wearable devices.

Protocol of a multicenter, single-blind, randomized, parallel controlled trial evaluating the effect of microbiological rapid on-site evaluation (M-ROSE) guiding anti-infection treatment in patients with severe hospital-acquired pneumonia.

INTRODUCTION: The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear. METHODS/DESIGN: This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria. ETHICS AND DISSEMINATION: This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001). TRIAL REGISTRATION: ClinicalTrials.gov NCT05300776. Registered on 25 March 2022.

Metatranscriptome of human lung microbial communities in a cohort of mechanically ventilated COVID-19 Omicron patients.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.

Clinical and microbiological characterization of Staphylococcus lugdunensis isolates obtained from clinical specimens in a hospital in China.

BACKGROUND: Several reports have associated Staphylococcus lugdunensis with the incidence of severe infection in humans; however, the frequency and prevalence of this microorganism and thus the propensity of its antimicrobial drug resistance is unknown in China. The objective of the current study was to determine the prevalence of Staphylococcus lugdunensis among six hundred and seventy non-replicate coagulase negative Staphylococcus (CoNS) isolates collected in a 12-month period from clinical specimens in the General Hospital of the People's Liberation Army in Beijing, China. RESULTS: Five (0.7%) of the 670 isolates of CoNS were identified as S. lugdunensis. Whereas three isolates were resistant to erythromycin, clindamycin, and penicillin and carried the ermC gene and a fourth one was resistant to cefoxitin and penicillin and carried the mecA gene, one isolate was not resistant to any of the tested antimicrobials. Pulse field gel electrophoretic analysis did not reveal widespread epidemiological diversity of the different isolates. CONCLUSION: Hence, even though S. lugdunensis may be yet unrecognized and undefined in China, it still might be the infrequent cause of infection and profound multi-drug resistance in the same population.