Impact of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid on Antimicrobial Stewardship in Patients With Lower Respiratory Tract Infections: A Retrospective Cohort Study.

BACKGROUND: The impact of metagenomic next-generation sequencing (mNGS) on antimicrobial stewardship in patients with lower respiratory tract infections (LRTIs) is still unknown. METHODS: This retrospective cohort study included patients who had LRTIs diagnosed and underwent bronchoalveolar lavage between September 2019 and December 2020. Patients who underwent both mNGS and conventional microbiologic tests were classified as the mNGS group, while those with conventional tests only were included as a control group. A 1:1 propensity score match for baseline variables was conducted, after which changes in antimicrobial stewardship between the 2 groups were assessed. RESULTS: A total of 681 patients who had an initial diagnosis of LRTIs and underwent bronchoalveolar lavage were evaluated; 306 patients were finally included, with 153 in each group. mNGS was associated with lower rates of antibiotic escalation than in the control group (adjusted odds ratio, 0.466 [95% confidence interval, .237-.919]; P = .02), but there was no association with antibiotic de-escalation. Compared with the control group, more patients discontinued the use of antivirals in the mNGS group. CONCLUSIONS: The use of mNGS was associated with lower rates of antibiotic escalation and may facilitate the cessation of antivirals, but not contribute to antibiotic de-escalation in patients with LRTIs.

Machine Learning Assisted Self-Powered Identity Recognition Based on Thermogalvanic Hydrogel for Intelligent Security.

Identity recognition as the first barrier of intelligent security plays a vital role, which is facing new challenges that are unable to meet the need of intelligent era due to low accuracy, complex configuration and dependence on power supply. Here, a finger temperature-driven intelligent identity recognition strategy is presented based on a thermogalvanic hydrogel (TGH) by actively discerning biometric characteristics of fingers. The TGH is a dual network PVA/Agar hydrogel in an H2O/glycerol binary solvent with [Fe(CN)6]3-/4- as a redox couple. Using a concave-arranged TGH array, the characteristics of users can be distinguished adequately even under an open environment by extracting self-existent intrinsic temperature features from five typical sites of fingers. Combined with machine learning, the TGH array can recognize different users with a high average accuracy of 97.6%. This self-powered identity recognition strategy is further applied to a smart lock, attaining a more reliable security protection from biometric characteristics than bare passwords. This work provides a promising solution for achieving better identity recognition, which has great advantages in intelligent security and human-machine interaction toward future Internet of everything.

Rapid chemical characterization of Danggui Buxue decoction using processed Astragali Radix and Angelicae Sinensis Radix based on diagnostic ion and molecular network.

Danggui Buxue decoction (DBD), a classic prescription of traditional Chinese medicine (TCM) for invigorating qi and generating blood, contains honey-processed Astragali Radix (HAR) and wine-processed Angelicae Sinensis Radix (WDG) in its original prescription. In this study, the compositions of DBD, WDG, and HAR were characterized using ultra-high-performance liquid chromatography coupled with the quadrupole-time-of-flight tandem mass spectrometry technique in combination with molecular network and diagnostic ion strategies. Finally, 200 compounds were identified in DBD, 114 compounds were identified in WDG, and 180 compounds were identified in HAR; there were 48 common compounds in total. The results demonstrated that compatibility led to changes in the chemical composition of TCM, and the qualitative method used in this study provided an effective data processing strategy for the characterization of components and the database for the study of the compounding mechanism of TCM.

High concentration of Cas12a effector tolerates more mismatches on ssDNA.

Rapid pathogen detection is critical for prompt treatment, interrupting transmission routes, and decreasing morbidity and mortality. The V-type CRISPR system had been used for rapid pathogen detection. However, whether single-stranded DNA in CRISPR system can cause false positives remains undetermined. Herein, we show that high molar concentration of Cas12a effector tolerated more mismatches on ssDNA and activated its trans-cleavage activity at six base matches. Reducing Cas12a and crRNA molar concentration increased the minimal base-match number required for Cas12a ssDNA activation to 11, which reducing nonspecific activation. We then established a Cas12a-based M tuberculosis detection system with a primer having an 8 bp overlap with crRNA. This system did not exhibit primer-induced false positives, and minimum detection copy reached 1 copy/uL (inputting 1-µL sample) in standard strains. The Cas12a-based M tuberculosis detection system showed 80.0% sensitivity and 100.0% specificity in verification using clinical specimens, compared with Xpert MTB/RIF, which showed 72.0% sensitivity and 90.9% specificity. All these results prove that appropriate concentration of cas12a effector can effectively perform nucleic acid detection.

Yeast YPK9 deficiency results in shortened replicative lifespan and sensitivity to hydrogen peroxide.

YPK9/YOR291W of Saccharomyces cerevisiae encodes a vacuolar membrane protein. Previous research has suggested that Ypk9p is similar to the yeast P5-type ATPase Spf1p and that it plays a role in the sequestration of heavy metals. In addition, bioinformatics analysis has suggested that Ypk9p is a homolog of human ATP13A2, which encodes a protein of the subfamily of P5 ATPases. However, no specific function of Ypk9p has been described to date. In this study, we found, for the first time, that YPK9 is involved in the oxidative stress response and modulation of the replicative lifespan (RLS). We found that YPK9 deficiency confers sensitivity to the oxidative stress inducer hydrogen peroxide accompanied by increased intracellular ROS levels, decreased mitochondrial membrane potential, abnormal mitochondrial function, and increased incidence of early apoptosis in budding yeast. More importantly, YPK9 deficiency can lead to a shortened RLS. In addition, we found that overexpression of the catalase-encoding gene CTA1 can reverse the phenotypic abnormalities of the ypk9Δ yeast strain. Collectively, these findings highlight the involvement of Ypk9p in the oxidative stress response and modulation of RLS.

Disease burden and prognostic factors for clinical failure in elderly community acquired pneumonia patients.

BACKGROUND: The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP). METHODS: 3011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis. RESULTS: The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH < 7.3, PaO2/FiO2 < 200 mmHg, sodium < 130 mmol/L, healthcare-associated pneumonia, white blood cells > 10,000/mm3, pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors. CONCLUSIONS: Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP. TRIAL REGISTRATION: A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb.

Effects of age, comorbidity and adherence to current antimicrobial guidelines on mortality in hospitalized elderly patients with community-acquired pneumonia.

BACKGROUND: Limited information exists on the clinical characteristics predictive of mortality in patients aged ≥65 years in many countries. The impact of adherence to current antimicrobial guidelines on the mortality of hospitalized elderly patients with community-acquired pneumonia (CAP) has never been assessed. METHODS: A total of 3131 patients aged ≥65 years were enrolled from a multi-center, retrospective, observational study initiated by the CAP-China network. Risk factors for death were screened with multivariable logistic regression analysis, with emphasis on the evaluation of age, comorbidities and antimicrobial treatment regimen with regard to the current Chinese CAP guidelines. RESULTS: The mean age of the study population was 77.4 ± 7.4 years. Overall in-hospital and 60-day mortality were 5.7% and 7.6%, respectively; these rates were three-fold higher in those aged ≥85 years than in the 65-74 group (11.9% versus 3.2% for in-hospital mortality and 14.1% versus 4.7% for 60-day mortality, respectively). The mortality was significantly higher among patients with comorbidities compared with those who were otherwise healthy. According to the 2016 Chinese CAP guidelines, 62.1% of patients (1907/3073) received non-adherent treatment. For general-ward patients without risk factors for Pseudomonas aeruginosa (PA) infection (n = 2258), 52.3% (1094/2090) were over-treated, characterized by monotherapy with an anti-pseudomonal ß-lactam or combination with fluoroquinolone + ß-lactam; while 71.4% of intensive care unit (ICU) patients (120/168) were undertreated, without coverage of atypical bacteria. Among patients with risk factors for PA infection (n = 815), 22.9% (165/722) of those in the general ward and 74.2% of those in the ICU (69/93) were undertreated, using regimens without anti-pseudomonal activity. The independent predictors of 60-day mortality were age, long-term bedridden status, congestive heart failure, CURB-65, glucose, heart rate, arterial oxygen saturation (SaO2) and albumin levels. CONCLUSIONS: Overtreatment in general-ward patients and undertreatment in ICU patients were critical problems. Compliance with Chinese guidelines will require fundamental changes in standard-of-care treatment patterns. The data included herein may facilitate early identification of patients at increased risk of mortality. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov ( NCT02489578 ).

A Highly Stable Copper-Based Catalyst for Clarifying the Catalytic Roles of Cu0 and Cu+ Species in Methanol Dehydrogenation.

Identification of the active copper species, and further illustration of the catalytic mechanism of Cu-based catalysts is still a challenge because of the mobility and evolution of Cu0 and Cu+ species in the reaction process. Thus, an unprecedentedly stable Cu-based catalyst was prepared by uniformly embedding Cu nanoparticles in a mesoporous silica shell allowing clarification of the catalytic roles of Cu0 and Cu+ in the dehydrogenation of methanol to methyl formate by combining isotope-labeling experiment, in situ spectroscopy, and DFT calculations. It is shown that Cu0 sites promote the cleavage of the O-H bond in methanol and of the C-H bond in the reaction intermediates CH3 O and H2 COOCH3 which is formed from CH3 O and HCHO, whereas Cu+ sites cause rapid decomposition of formaldehyde generated on the Cu0 sites into CO and H2 .

Importance of Distending Stomach With Fluid for Ultrasound Detection of Focal Lesion in the Elongated Left Lobe of the Liver.

OBJECTIVES: The purpose of this study was to evaluate distending the stomach with water for ultrasound detection of focal lesions in the elongated left lobe of the liver. METHODS: A total of 13,277 patients undergoing liver ultrasound were evaluated for the presence of an elongated left lobe of the liver and a focal lesion. Patients with an elongated left lobe of the liver had their stomach distended with oral water for further evaluation of a focal lesion. A portion of the patients had computed tomography (CT) examinations, which were compared with the ultrasound studies. RESULTS: A total of 643 patients were found with elongated left lobe of the liver by ultrasound; of them, 451 underwent CT, 259 out of the 451 patients meeting the inclusion criteria underwent second ultrasound and final analysis, and 16 of these 259 patients had focal lesion in the elongated left lobe of the liver on CT study. The sonographic visualization of the liver and spleen at the same scan view before and after distending the stomach were 7% (7 of 100) and 100% (100 of 100), respectively (P < .001). The sonographic detection of the lesions before and after distending the stomach were zero and 87.5%, respectively (P < .001). CONCLUSIONS: Distending the stomach with water can greatly increase ultrasound detection of focal lesions in the elongated left lobe of the liver.

Thermoelectric Hydrogel Electronic Skin for Passive Multimodal Physiological Perception.

Electronic skins (e-skins) are being extensively researched for their ability to recognize physiological data and deliver feedback via electrical signals. However, their wide range of applications is frequently restricted by the indispensableness of external power supplies and single sensory function. Here, we report a passive multimodal e-skin for real-time human health assessment based on a thermoelectric hydrogel. The hydrogel network consists of poly(vinyl alcohol)/low acyl gellan gum with [Fe(CN)6]4-/3- as the redox couple. The introduction of glycerol and Li+ furnishes the gel-based e-skin with antidrying and antifreezing properties, a thermopower of 2.04 mV K-1, fast self-healing in less than 10 min, and high conductivity of 2.56 S m-1. As a prospective application, the e-skin can actively perceive multimodal physiological signals without the need for decoupling, including body temperature, pulse rate, and sweat content, in real time by synergistically coupling sensing and transduction. This work offers a scientific basis and designs an approach to develop passive multimodal e-skins and promotes the application of wearable electronics in advanced intelligent medicine.

Thermogalvanic hydrogel-based e-skin for self-powered on-body dual-modal temperature and strain sensing.

Sensing of both temperature and strain is crucial for various diagnostic and therapeutic purposes. Here, we present a novel hydrogel-based electronic skin (e-skin) capable of dual-mode sensing of temperature and strain. The thermocouple ion selected for this study is the iodine/triiodide (I-/I3-) redox couple, which is a common component in everyday disinfectants. By leveraging the thermoelectric conversion in conjunction with the inherent piezoresistive effect of a gel electrolyte, self-powered sensing is achieved by utilizing the temperature difference between the human body and the external environment. The composite hydrogels synthesized from polyvinyl alcohol (PVA) monomers using a simple freeze‒thaw method exhibit remarkable flexibility, extensibility, and adaptability to human tissue. The incorporation of zwitterions further augments the resistance of the hydrogel to dehydration and low temperatures, allowing maintenance of more than 90% of its weight after 48 h in the air. Given its robust thermal current response, the hydrogel was encapsulated and then integrated onto various areas of the human body, including the cheeks, fingers, and elbows. Furthermore, the detection of the head-down state and the monitoring of foot movements demonstrate the promising application of the hydrogel in supervising the neck posture of sedentary office workers and the activity status. The successful demonstration of self-powered on-body temperature and strain sensing opens up new possibilities for wearable intelligent electronics and robotics.

Combining WO3@AuNPs with Poly(amidoamine) Allows Sensitive Electrochemical Detection of DR1 Based on Dual Signal Amplification.

Down-regulator of transcription 1 (DR1) is considered as a biomarker of hashimoto's thyroiditis (HT), which is a risk factor for thyroid cancer. Here, a label-free electrochemical biosensor for DR1 detection was constructed based on polyamidoamine (PAMAM) polymer and the nanocomposite (WO3@AuNPs) composed of tungsten trioxide (WO3) and gold nanoparticles (AuNPs). WO3@AuNPs was obtained by combining monolayer WO3 nanosheets, which has high conductivity, and AuNPs. The modification of WO3@AuNPs can not only increase the conductivity of the electrode but also provide more active sites for signaling units, thus greatly improve the sensitivity of the sensor. The polymer PAMAM is biocompatible and non-immunogenic, and its end functional group can bind to the target molecules, providing them with more binding sites and thus improving the sensitivity of the sensor. Under optimal conditions, the label-free biosensor showed a good linear relationship between the logarithm of DR1 concentration and the impedance in the range of 10 fg ⋅ mL-1 to 100 ng ⋅ mL-1, with a detection limit as low as 0.3 fg ⋅ mL-1. Besides, this label-free electrochemical platform exhibited satisfactory selectivity and anti-interference capability in human serum samples. Therefore, this method has considerable potential in clinical detection of DR1.

Effect of ATG8 or SAC1 deficiency on the cell proliferation and lifespan of the long-lived PMT1 deficiency yeast cells.

Autophagy is pivotal in maintaining intracellular homeostasis, which involves various biological processes, including cellular senescence and lifespan modulation. Being an important member of the protein O-mannosyltransferase (PMT) family of enzymes, Pmt1p deficiency can significantly extend the replicative lifespan (RLS) of yeast cells through an endoplasmic reticulum (ER) unfolded protein response (UPR) pathway, which is participated in protein homeostasis. Nevertheless, the mechanisms that Pmt1p regulates the lifespan of yeast cells still need to be explored. In this study, we found that the long-lived PMT1 deficiency strain (pmt1Δ) elevated the expression levels of most autophagy-related genes, the expression levels of total GFP-Atg8 fusion protein and free GFP protein compared with wild-type yeast strain (BY4742). Moreover, the long-lived pmt1Δ strain showed the greater dot-signal accumulation from GFP-Atg8 fusion protein in the vacuole lumen through a confocal microscope. However, deficiency of SAC1 or ATG8, two essential components of the autophagy process, decreased the cell proliferation ability of the long-lived pmt1Δ yeast cells, and prevented the lifespan extension. In addition, our findings demonstrated that overexpression of ATG8 had no potential effect on the RLS of the pmt1Δ yeast cells, and the maintained incubation of minimal synthetic medium lacking nitrogen (SD-N medium as starvation-induced autophagy) inhibited the cell proliferation ability of the pmt1Δ yeast cells with the culture time, and blocked the lifespan extension, especially in the SD-N medium cultured for 15 days. Our results suggest that the long-lived pmt1Δ strain enhances the basal autophagy activity, while deficiency of SAC1 or ATG8 decreases the cell proliferation ability and shortens the RLS of the long-lived pmt1Δ yeast cells. Moreover, the maintained starvation-induced autophagy impairs extension of the long-lived pmt1Δ yeast cells, and even leads to the cell death.

Low-Grade Thermal Energy Harvesting and Self-Powered Sensing Based on Thermogalvanic Hydrogels.

Thermoelectric cells (TEC) directly convert heat into electricity via the Seebeck effect. Known as one TEC, thermogalvanic hydrogels are promising for harvesting low-grade thermal energy for sustainable energy production. In recent years, research on thermogalvanic hydrogels has increased dramatically due to their capacity to continuously convert heat into electricity with or without consuming the material. Until recently, the commercial viability of thermogalvanic hydrogels was limited by their low power output and the difficulty of packaging. In this review, we summarize the advances in electrode materials, redox pairs, polymer network integration approaches, and applications of thermogalvanic hydrogels. Then, we highlight the key challenges, that is, low-cost preparation, high thermoelectric power, long-time stable operation of thermogalvanic hydrogels, and broader applications in heat harvesting and thermoelectric sensing.

Self-Powered, Non-Toxic, Recyclable Thermogalvanic Hydrogel Sensor for Temperature Monitoring of Edibles.

Thermogalvanic hydrogel, an environmentally friendly power source, enable the conversion of low-grade thermal energy to electrical energy and powers microelectronic devices in a variety of scenarios without the need for additional batteries. Its toxicity, mechanical fragility and low output performance are a hindrance to its wide application. Here, we demonstrate thermoelectric gels with safe non-toxic, recyclable, highly transparent and flexible stretchable properties by introducing gelatin as a polymer network and SO3/42- as a redox electric pair. When the temperature difference is 10 K, the gel-based thermogalvanic cell achieves an open-circuit voltage of about 16.2 mV with a maximum short-circuit current of 39 µA. Furthermore, we extended the application of the Gel-SO3/42- gel to monitor the temperature of hot or cold food, enabling self-powered sensing for food temperature detection. This research provides a novel concept for harvesting low-grade thermal energy and achieving safe and harmless self-driven temperature monitoring.

Integration of diagnostic ions, molecular network and chemometrics to illustrate the chemical mechanism of Radix Astragali processed with honey.

Radix Astragali (RA) is one of the most frequently used traditional Chinese medicine (TCM) in China, and honey-processed RA (HRA) is its common processing product. Thus far, their comprehensive chemical differences are not well understood. In this work, an integrated approach using Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) combined with diagnostic ions, molecular network (MN) and chemometrics was established to profile their chemical characterizations and illustrate the chemical mechanism of RA processed with honey. A total of 226 compounds were tentatively identified including 50 flavonoid glycosides, 26 flavonoid aglycone, 56 saponins, 30 organic acids, 18 amino acids, 3 coumarins and 43 other compounds, of which 33 compounds were characterized according to MN. Their chemical differences were further investigated by integrating of multivariate statistical analysis, student's t-test analysis, linear regression analysis and MN. Consequently, multivariate statistical analysis showed that the raw and processed RA were different form each other. Besides, 33 different compounds were found to be significantly altered by student's t-test analysis. Apart from this, linear regression analysis indicated 42 and 120 compounds underwent the significant varieties. The potential chemical reactions induced by honey-processing, such as possible hydrolysis reactions and isomerization reactions, were speculated based on these variations coupled the areas changes of the nodes in MN. This study provided an efficient strategy to illustrate the chemical mechanism of TCM processing.

Degradation of vinyl ester resin and its composites via cleavage of ester bonds to recycle valuable chemicals and produce polyurethane.

Vinyl ester resins (VER) and its composites are widely used in chemical industry and municipal engineering. However, its dense three-dimensional network structure makes its degradation and recycling a great challenge. Herein, a novel, efficient and green degradation system gamma-valerolactone (GVL)-H2O/p-toluene sulfonic (PTSA) was developed to degrade VER and its composites. VER was completely degraded in the GVL-H2O/PTSA at 210 °C and 0.6 MPa. By combing SEM-EDS, IR, NMR, GPC and MALDI-TOF-MS analysis, it was clarified that VER swelled well in GVL, allowing the transfer of PTSA and H2O through the resin matrix. The ester bonds in VER were cleaved via hydrolysis with H2O catalyzed by the sulfonic acid of PTSA, and high value-added polymer products, i.e., copolymer of styrene and methacrylic acid (SMAA) and bisphenol-A diglycidyl ether (DGEBA), were recycled, which accounted for ca. 87.0 wt% of raw VER. DGEBA can be recycled to prepare a new PU material. The GVL-H2O/PTSA system was also effective for degrading UPR and VER-containing composites. This work provides a practical strategy for chemical degradation and recovery of thermoset VER resins.

Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1.

Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate to all blood cell types. HSCs and their differentiated progeny show sex/gender differences. The fundamental mechanisms remain largely unexplored. We previously reported that latexin (Lxn) deletion increased HSC survival and repopulation capacity in female mice. Here, we find no differences in HSC function and hematopoiesis in Lxn knockout (Lxn-/-) male mice under physiologic and myelosuppressive conditions. We further find that Thbs1, a downstream target gene of Lxn in female HSCs, is repressed in male HSCs. Male-specific high expression of microRNA 98-3p (miR98-3p) contributes to Thbs1 suppression in male HSCs, thus abrogating the functional effect of Lxn in male HSCs and hematopoiesis. These findings uncover a regulatory mechanism involving a sex-chromosome-related microRNA and its differential control of Lxn-Thbs1 signaling in hematopoiesis and shed light on the process underlying sex dimorphism in both normal and malignant hematopoiesis.