Molecular recognition of trehalose and trehalose analogues by Mycobacterium tuberculosis LpqY-SugABC.

Trehalose plays a crucial role in the survival and virulence of the deadly human pathogen Mycobacterium tuberculosis (Mtb). The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the sole pathway for trehalose to enter Mtb. The substrate-binding protein, LpqY, which forms a stable complex with the translocator SugABC, recognizes and captures trehalose and its analogues in the periplasmic space, but the precise molecular mechanism for this process is still not well understood. This study reports a 3.02-Å cryoelectron microscopy structure of trehalose-bound Mtb LpqY-SugABC in the pretranslocation state, a crystal structure of Mtb LpqY in a closed form with trehalose bound and five crystal structures of Mtb LpqY in complex with different trehalose analogues. These structures, accompanied by substrate-stimulated ATPase activity data, reveal how LpqY recognizes and binds trehalose and its analogues, and highlight the flexibility in the substrate binding pocket of LpqY. These data provide critical insights into the design of trehalose analogues that could serve as potential molecular probe tools or as anti-TB drugs.

Bacitracin-resistant Staphylococcus aureus induced in chicken gut and in vitro under bacitracin exposure.

It is common knowledge that prolonged and excessive use of antibiotics can lead to antimicrobial resistance. However, the characteristics and mechanism of resistant-bacteria induced by clinically recommended and prophylactic dose drugs remain largely unclear. This study aimed to observe the trends of drug resistance of the bacitracin-susceptible Staphylococcus aureus strain FS127 under exposure to bacitracin (BAC), which were induced in vitro and in chicken gut. Antimicrobial susceptibility testing was used to detect the susceptibility of S. aureus induced in vitro and in the chicken gut to gentamicin, chloramphenicol, tetracycline, doxycycline, penicillin and chloramphenicol. The research results showed that bacitracin could induce drug resistance in S. aureus both in vitro and in vivo. The bacitracin-resistance rate of S. aureus isolated from chicken gut was positively correlated with the dose and time of bacitracin administration. The findings revealed that bacitracin-resistant S. aureus induced in vivo had enhanced susceptibility to chloramphenicol but no such change in vitro. Meanwhile, RT-qPCR assay was used to detect the expression levels of vraD, braD, braR and bacA in typical strains with different bacitracin-resistance levels. It was found that BacA may play a key role in the bacitracin resistance of S. aureus. In conclusion, this work reveals the characteristics and mechanism of bacitracin-resistant S. aureus induced by bacitracin in vivo and in vitro respectively.

Non-invasive methods for heart rate measurement in fish based on photoplethysmography.

Heart rate is a crucial physiological indicator for fish, but current measurement methods are often invasive or require delicate manipulation. In this study, we introduced two non-invasive and easy-to-operate methods based on photoplethysmography, namely reflectance-type photoplethysmography (PPG) and remote photoplethysmography (rPPG), which we applied to the large yellow croaker (Larimichthys crocea). PPG showed perfect synchronization with electrocardiogram (ECG), with a Pearson's correlation coefficient of 0.99999. For rPPG, the results showed good agreement with ECG. Under active provision of green light, the Pearson's correlation coefficient was 0.966, surpassing the value of 0.947 under natural light. Additionally, the root mean square error was 0.810, which was lower than the value of 1.30 under natural light, indicating not only that the rPPG method had relatively high accuracy but also that green light may have the potential to further improve its accuracy.

Comprehensive analysis of MAPK gene family in upland cotton (Gossypium hirsutum) and functional characterization of GhMPK31 in regulating defense response to insect infestation.

KEY MESSAGE: The transcriptomic, phenotypic and metabolomic analysis of transgenic plants overexpressing GhMPK31 in upland cotton revealed the regulation of H2O2 burst and the synthesis of defensive metabolites by GhMPK31. Mitogen-activated protein kinases (MAPKs) are a crucial class of protein kinases, which play an essential role in various biological processes in plants. Upland cotton (G. hirsutum) is the most widely cultivated cotton species with high economic value. To gain a better understanding of the role of the MAPK gene family, we conducted a comprehensive analysis of the MAPK gene family in cotton. In this study, a total of 55 GhMPK genes were identified from the whole genome of G. hirsutum. Through an investigation of the expression patterns under diverse stress conditions, we discovered that the majority of GhMPK family members demonstrated robust responses to abiotic stress, pathogen stress and pest stress. Furthermore, the overexpression of GhMPK31 in cotton leaves led to a hypersensitive response (HR)-like cell death phenotype and impaired the defense capability of cotton against herbivorous insects. Transcriptome and metabolomics data analysis showed that overexpression of GhMPK31 enhanced the expression of H2O2-related genes and reduced the accumulation of defensive related metabolites. The direct evidence of GhMPK31 interacting with GhRBOHB (H2O2-generating protein) were found by Y2H, BiFC, and LCI. Therefore, we propose that the increase of H2O2 content caused by overexpression of GhMPK31 resulted in HR-like cell death in cotton leaves while reducing the accumulation of defensive metabolites, ultimately leading to a decrease in the defense ability of cotton against herbivorous insects. This study provides valuable insights into the function of MAPK genes in plant resistance to herbivorous insects.

Using a smartphone-based self-management platform to study sex differences in Parkinson's disease: multicenter, cross-sectional pilot study.

BACKGROUND: Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson's disease (PD) is hardly extensively researched. METHODS: A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. RESULTS: Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P < 0.001). For motor symptoms, a higher proportion of patients reporting dyskinesia was observed in the female group. For non-motor symptoms, there is a higher percentage (P < 0.001) as well as severity (P = 0.016) of depression in the female group. More male patients reported hyposmia, lisp, drooling, dysuria, frequent urination, hypersexuality, impotence, daytime sleepiness, and apathy than females (P < 0.05). In contrast, more female patients reported headache, palpation, body pain, anorexia, nausea, urinal incontinence, anxiety, insomnia (P < 0.05) than males. CONCLUSIONS: We provide evidence for sex differences in PD through the data collected from our platform. These results highlighted the importance of gender in clinical decision-making, and also support the feasibility of remote PRO measurement through a smartphone-based self-management platform in patients with PD.

ARHGAP25 suppresses the development of breast cancer by an ARHGAP25/Wnt/ASCL2 feedback loop.

Downregulation of ARHGAP25 was found in the tumor samples from breast cancer patients and five breast cancer cell lines. However, its precise role and molecular mechanisms in breast cancer remain completely unknown. Herein, we found that knockdown of ARHGAP25 in breast cancer cells promoted proliferation, migration and invasion of breast cancer cells. Mechanistically, ARHGAP25 silence facilitated the activation of the Wnt/ß-catenin pathway and the upregulation of its downstream molecules (including c-Myc, Cyclin D1, PCNA, MMP2, MMP9, Snail and ASCL2) by directly regulating Rac1/PAK1 in breast cancer cells. In vivo xenograft experiments indicated ARHGAP25 silence promoted tumor growth and activated the Wnt/ß-catenin pathway. In contrast, overexpression of ARHGAP25 in vitro and in vivo impeded all of the above cancer properties. Intriguingly, ASCL2, a downstream target of the Wnt/ß-catenin pathway, transcriptionally repressed the expression of ARHGAP25 and therefore constituted a negative feedback loop. Moreover, bioinformatics analysis indicated that ARHGAP25 was significantly correlated with tumor immune cell infiltration and the survival of patients with different immune cell subgroups in breast cancer. Collectively, our work revealed that ARHGAP25 suppressed tumor progression of breast cancer. It provides a novel insight for the treatment of breast cancer.

In Vivo 18 F-Florzolotau Tau Positron Emission Tomography Imaging in Parkinson's Disease Dementia.

BACKGROUND: Tau pathology is observed during autopsy in many patients with Parkinson's disease dementia (PDD). Positron emission tomography (PET) imaging using the tracer 18 F-florzolotau has the potential to capture tau accumulation in the living brain. OBJECTIVE: The aim was to describe the results of 18 F-florzolotau PET/CT (computed tomography) imaging in patients with PDD. METHODS: Ten patients with PDD, 9 with Parkinson's disease with normal cognition (PD-NC), and 9 age-matched healthy controls (HCs) were enrolled. Clinical assessments and 18 F-florzolotau PET/CT imaging were performed. RESULTS: 18 F-Florzolotau uptake was significantly higher in the cortical regions of patients with PDD compared with both PD-NC and HCs, especially in the temporal lobe. Notably, 18 F-florzolotau uptake in the occipital lobe of patients with PDD showed a significant correlation with cognitive impairment as reflected by Mini-Mental State Examination (MMSE) scores. CONCLUSIONS: 18 F-Florzolotau PET imaging can effectively capture the occurrence of tau pathology in patients with PDD, which was also linked to MMSE scores. © 2022 International Parkinson and Movement Disorder Society.

SPOPL induces tumorigenicity and stemness in glioma stem cells by activating Notch signaling.

OBJECTIVE: Recent studies have increasingly shown that glioma stem cells (GSCs) are extremely important for developing and treating glioblastoma multiforme (GBM). The Broad-complex, Tram-track, and Bric-a-brac protein family is functionally related to a variety of tumor stem cells, and the role of SPOPL as a member of this family in GSCs deserves to be investigated. METHODS: To investigate the expression of SPOPL in GSCs and its impact on the prognosis of GBM patients by using clinical specimens, patient-derived primary GSCs and public databases. In vivo and in vitro, the effect of SPOPL on the proliferation, self-renewal, and differentiation ability of GSCs was explored. Probing the mechanism by which SPOPL affects the biological function of GSCs using RNA sequencing (RNA-seq) and rescue experiments. RESULTS: The expression of SPOPL was significantly upregulated in GSCs and GBM, and patients with high SPOPL expression had a poorer prognosis. SPOPL enhanced the proliferation and self-renewal ability of GSCs and enhanced the tumorigenicity of GSCs. The Notch signaling pathway was significantly inhibited in SPOPL knockdown GSCs. Activation or inhibition of the Notch signaling pathway rescued changes in the biological function of GSCs caused by altered SPOPL expression. CONCLUSION: SPOPL can be used as a potential prognostic biomarker for GBM in clinical work and promotes the proliferation and stemness of GSCs by activating the Notch signaling pathway, which may be a potential molecule for targeting GSCs to treat GBM.

Optimization of the Double-Expansion Film-Cooling Hole Using CFD.

Film cooling is a major cooling technique used in modern gas turbines and air engines. The geometry of film-cooling holes is the fundamental aspect affecting the cooling performance. In this paper, a new cooling configuration called the double-expansion film-cooling hole has been put forward, which yields better performance than the widely used shaped holes and is easy to manufacture. The double-expansion holes at inclination angles of α=30∘, 45∘, and 60∘ are optimized using the genetic algorithm and the Kriging surrogate model, which is trained by CFD data randomly sampled using the Latin hypercube method. The numerically optimized double-expansion holes at different inclination angles were experimentally evaluated and compared with the optimized single-expansion laid-back fan-shaped holes, and the optimized double-expansion hole at α=30∘ was manually modified based on experiment results. Compared with the optimal single-expansion holes, the area-averaged cooling effectiveness of the double-expansion holes was increased by 34.5% at α=30∘, by 27.8% at α=45∘, and basically the same at α=60∘, showing the benefit of the double-expansion concept. The loss mechanism of film cooling was also analyzed in the perspective of the entropy generation rate, showing the optimal double-expansion holes have 21% less loss compared to a baseline narrow single-expansion hole. It was also found that CFD sometimes predicts a different trend from the experiment in optimization, and the experimental validation is necessary.

Development of Individual Variability in Brain Functional Connectivity and Capability across the Adult Lifespan.

Individual variability exists in both brain function and behavioral performance. However, changes in individual variability in brain functional connectivity and capability across adult development and aging have not yet been clearly examined. Based on resting-state functional magnetic resonance imaging data from a large cohort of participants (543 adults, aged 18-88 years), brain functional connectivity was analyzed to characterize the spatial distribution and differences in individual variability across the adult lifespan. Results showed high individual variability in the association cortex over the adult lifespan, whereas individual variability in the primary cortex was comparably lower in the initial stage but increased with age. Individual variability was also negatively correlated with the strength/number of short-, medium-, and long-range functional connections in the brain, with long-range connections playing a more critical role in increasing global individual variability in the aging brain. More importantly, in regard to specific brain regions, individual variability in the motor cortex was significantly correlated with differences in motor capability. Overall, we identified specific patterns of individual variability in brain functional structure during the adult lifespan and demonstrated that functional variability in the brain can reflect behavioral performance. These findings advance our understanding of the underlying principles of the aging brain across the adult lifespan and suggest how to characterize degenerating behavioral capability using imaging biomarkers.

A Wavelet Packet Transform and Convolutional Neural Network Method Based Ultrasonic Detection Signals Recognition of Concrete.

This paper proposes a new intelligent recognition method for concrete ultrasonic detection based on wavelet packet transform and a convolutional neural network (CNN). To validate the proposed data-based method, a case study is presented where the K-fold cross-validation was adopted to produce the performance analysis and classification experiments. Moreover, three evaluation indicators, precision, recall, and F-score, are calculated for analyzing the classification performance of the trained models. As a result, the obtained four-classifying CNN reaches more than 99% detection accuracy while the lowest recognition accuracy is not less than 92.5% on the testing dataset for the six-classifying CNN model. Compared with the existing stochastic configuration network (SCN) models, the presented method achieves the design objective with better recognition performance. The calculation results of the six-classifying and five-classifying models and related research clearly indicate the remaining challenging tasks for intelligent recognition algorithms in extracting features and classifying mass data from various concrete defects precisely and efficiently.

Soil carbon persistence governed by plant input and mineral protection at regional and global scales.

Elucidating the processes underlying the persistence of soil organic matter (SOM) is a prerequisite for projecting soil carbon feedback to climate change. However, the potential role of plant carbon input in regulating the multi-layer SOM preservation over broad geographic scales remains unclear. Based on large-scale soil radiocarbon (∆14 C) measurements on the Tibetan Plateau, we found that plant carbon input was the major contributor to topsoil carbon destabilisation despite the significant associations of topsoil ∆14 C with climatic and mineral variables as well as SOM chemical composition. By contrast, mineral protection by iron-aluminium oxides and cations became more important in preserving SOM in deep soils. These regional observations were confirmed by a global synthesis derived from the International Soil Radiocarbon Database (ISRaD). Our findings illustrate different effects of plant carbon input on SOM persistence across soil layers, providing new insights for models to better predict multi-layer soil carbon dynamics under changing environments.

Imaging in turbid water based on a Hadamard single-pixel imaging system.

Underwater imaging is a challenging task because of the large amounts of noise and the scattering nature of water. Conventional optical methods cannot realize clear imaging in underwater conditions owing to the limitations of low sensitivity, geometrical aberrations, and the narrow spectrum of photoelectric detectors. By contrast, single-pixel imaging (SPI) is a promising tool for imaging in poor-visibility environments. Nevertheless, this challenge is faced even when using traditional SPI methods in highly turbid underwater environments. In this work, we propose a Hadamard single-pixel imaging (HSI) system that outperforms other imaging modes in turbid water imaging. The effects of laser power, projection rate, and water turbidity on the final image quality are systematically investigated. Results reveal that compared with the state-of-the-art SPI techniques, the proposed HSI system is more promising for underwater imaging because of its high resolution and anti-scattering capabilities.

Clinical characteristics and a decision tree model to predict death outcome in severe COVID-19 patients.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) spreads rapidly among people and causes a pandemic. It is of great clinical significance to identify COVID-19 patients with high risk of death. METHODS: A total of 2169 adult COVID-19 patients were enrolled from Wuhan, China, from February 10th to April 15th, 2020. Difference analyses of medical records were performed between severe and non-severe groups, as well as between survivors and non-survivors. In addition, we developed a decision tree model to predict death outcome in severe patients. RESULTS: Of the 2169 COVID-19 patients, the median age was 61 years and male patients accounted for 48%. A total of 646 patients were diagnosed as severe illness, and 75 patients died. An older median age and a higher proportion of male patients were found in severe group or non-survivors compared to their counterparts. Significant differences in clinical characteristics and laboratory examinations were found between severe and non-severe groups, as well as between survivors and non-survivors. A decision tree, including three biomarkers, neutrophil-to-lymphocyte ratio, C-reactive protein and lactic dehydrogenase, was developed to predict death outcome in severe patients. This model performed well both in training and test datasets. The accuracy of this model were 0.98 in both datasets. CONCLUSION: We performed a comprehensive analysis of COVID-19 patients from the outbreak in Wuhan, China, and proposed a simple and clinically operable decision tree to help clinicians rapidly identify COVID-19 patients at high risk of death, to whom priority treatment and intensive care should be given.

Indications for and contraindications of immune checkpoint inhibitors in cancer patients with COVID-19 vaccination.

The COVID-19 pandemic has lasted over 1 year and will not disappear in a short time. There is no specific remedy against the virus as yet. Vaccination is thus far one of the most important strategies for preventing COVID-19. Cancer patients with COVID-19 have a higher mortality because of immunosuppression. Immune checkpoint inhibitors (ICIs) are a novel anticancer strategy for blocking inhibitory pathways, which are related to the immune response. There is a question regarding whether COVID-19 vaccination and ICI treatment impact each other in cancer patients. This review explores both sides of the relationship between ICI treatment and COVID-19 vaccination and suggests good efficacy and safety of ICI treatment after COVID-19 vaccination as well as little impact on the virus protection and toxicity associated with COVID-19 vaccination during ICI treatment.

Lay abstract The COVID-19 pandemic has lasted over 1 year. Vaccination is a promising strategy for preventing COVID-19. Cancer patients are prone to infection with COVID-19, and these patients have high mortality. Immune checkpoint inhibitors (ICIs) are a novel anticancer strategy. Whether COVID-19 vaccination and ICI treatment impact each other in cancer patients remains unknown. This review explores both sides of the relationship between ICI treatment and COVID-19 vaccination and suggests good efficacy and safety of ICI treatment after COVID-19 vaccination as well as little impact on the virus protection and toxicity associated with COVID-19 vaccination during ICI treatment.

Design and Performance Analysis of an Ultrasonic System for Health Monitoring of Concrete Structure.

The development and research of an ultrasonic-based concrete structural health monitoring system encounters a variety of problems, such as demands of decreasing complexity, high accuracy, and extendable system output. Aiming at these requirements, a low-cost extendable system based on FPGA with adjustable system output has been designed, and the performance has been evaluated by different assessment parameters set in this paper. Besides the description of the designed system and the experiments in air medium, the residual similarity and Pearson correlation coefficients of experimental and theoretical data have been used to evaluate the submodules' output. The output performance of the overall system is evaluated by the Pearson correlation coefficient, root-mean-square error (RMSE), and magnitude-squared coherence with 40 experimental data. The maximum, median, minimum, and mean values in three-parameter datasets are analyzed for discussing the working condition of the system. The experimental results show that the system works stably and reliably with tunable frequency and amplitude output.

The clinical characteristic and outcome of skin and soft tissue infection in immunosuppressive patients with nephrotic syndrome.

OBJECTIVE: Skin and soft tissue infection (SSTI) is the most common of infectious diseases with high morbidity and mortality. However, the clinical characteristics of SSTI in patients with nephrotic syndrome (NS), especially in those patients who received immunosuppressive therapy, are still lacking. The present study was conducted to investigate the clinical characteristics and outcomes of SSTI in patients with NS. METHODS: A retrospective study was carried out among the patients diagnosed with NS and SSTI, who have priorly received or currently have been receiving immunosuppressive therapy between April 2011 and January 2019; the clinical profile included patient's baseline characteristics, clinical presentation, microbiological findings, treatment, and prognosis. RESULTS: A total of 70 patients were analyzed. Results showed that more than half of the patients were under 35 years old, and moderate infection was the most common type of SSTI. Leg and cellulitis were the most common site of lesion and the typical clinical manifestation of SSTI, respectively. Patients in the severe infection group have a higher level of procalcitonin (PCT) and C-reactive protein (CRP), while a lower level of albumin, CD4+ T and CD8+ T cell count. Moreover, the gram-negative bacteria were the primary pathogens of SSTI in patients with NS, and Klebsiella pneumoniae were the most frequent strains isolated from those patients. Besides, patients in the mild and moderate infection groups experienced a better outcome. CONCLUSIONS: Patients with NS and SSTI usually showed a satisfying outcome with proper anti-infection treatment, but severe SSTI can be life-threatening.

Iminium Ion and N-Hydroxyimide as the Surrogate Components in DEAD-Promoted Oxidative Ugi Variant.

A practical metal-free oxidative Ugi-type three-component assembly has been achieved efficiently, employing a tertiary-amine-derived iminium ion as an imine surrogate, N-hydroxyimide as an acid surrogate, and DEAD as an oxidant. This dual-surrogate Ugi variant proceeded with a broad substrate scope and desired functional group tolerance, leading to a wide range of N-alkyl- N-acyl aminophthalimide and N-alkyl- N-acylaminosuccinimide derivatives in good isolated yields.

Carbon-Electrode-Tailored All-Inorganic Perovskite Solar Cells To Harvest Solar and Water-Vapor Energy.

Moisture is the worst enemy for state-of-the-art perovskite solar cells (PSCs). However, the flowing water vapor within nanoporous carbonaceous materials can create potentials. Therefore, it is a challenge to integrate water vapor and solar energies into a single PSC device. We demonstrate herein all-inorganic cesium lead bromide (CsPbBr3 ) solar cells tailored with carbon electrodes to simultaneously harvest solar and water-vapor energy. Upon interfacial modification and plasma treatment, the bifunctional PSCs yield a maximum power conversion efficiency up to 9.43 % under one sun irradiation according to photoelectric conversion principle and a power output of 0.158 µW with voltage of 0.35 V and current of 0.45 µA in 80 % relative humidity through the flowing potentials at the carbon/water interface. The initial efficiency is only reduced by 2 % on exposing the inorganic PSC with 80 % humidity over 40 days. The successful realization of physical proof-of-concept multi-energy integrated solar cells provides new opportunities of maximizing overall power output.

Sensitive detection of acid phosphatase based on graphene quantum dots nanoassembly.

In this study, we report a convenient label-free fluorescence biosensor for the detection of acid phosphatase based on the aggregation-caused quenching of graphene quantum dots (GQDs). The fluorescence of GQDs could be quenched by poly-(dimethyl diallyl ammonium chloride) (PDDA); the high efficiency of the quenching was caused by the non-covalent binding of positively charged PDDA to negatively charged GQDs through electrostatic interactions, aggregating to form a GQDs-PDDA complex. Addition of sodium hexametaphosphate (NaPO3)6 could effectively turn on the quenched fluorescence due to the stronger electrostatic interactions between positively charged PDDA and negatively charged (NaPO3)6. The introduction of acid phosphatase (ACP) would lead to the breakdown of (NaPO3)6 into small fragments and disassemble the complex of PDDA-(NaPO3)6. As a result, the recovered fluorescence could be quenched again by the addition of ACP. Quantitative evaluation of ACP activity in a broad range from 30 nU mL(-1) to 420 nU mL(-1) with a detection limit of 12 nU mL(-1) can be achieved in this way, endowing the assay with sufficiently high sensitivity for practical detection of ACP in human serum.