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Background: Climate change has led to the frequent occurrence of high-temperature weather, which has various adverse effects on health, ranging from blood metabolism to systemic organ function. In particular, the sequelae of heat stress injury in most people are related to the nervous system. However, the mechanisms between heat stress and mental health conditions, especially heat stress and anxiety, remain unclear. Objective: We attempted to elucidate the effect of heat exposure intervention on anxiety levels in the population and its mechanism. Methods: We first carried out a randomized controlled trial in 20 college students in Beijing, China, to observe the results of the effects of heat exposure intervention on human anxiety. Then, we collected blood samples before and after heat exposure experiment and used metabolomic and transcriptomic approaches to quantify serum metabolites and ELISA measurements to explore the underlying mechanisms. Results: We found that even 1.5-hour heat exposure intervention significantly increased anxiety levels. Heat stress-induced anxiety was mediated by the activation of the HPA axis, inflammation, oxidative stress, and subsequently unbalanced neurotransmitters. Metabolites such as BDNF, GABA, and glucocorticoids released by the adrenal glands are biomarkers of heat stress-induced anxiety. Conclusions: We have demonstrated a causal link between heat stress and anxiety, explored possible biological pathway between heat stress and anxiety. Heat stress can cause the activation of the HPA axis and lead to changes in the body's metabolism, resulting in a series of changes such as inflammation and oxidative stress, leading to anxiety. This study reveals hidden health cost of climate change that has been underexplored, and also reminds us the importance of immediate climate actions.

The regulator of expression of virion (Rev) protein binds specifically to the Rev-responsive element (RRE) RNA in order to regulate the expression of the human immunodeficiency virus (HIV)-1 genes. Fluorescence indicator displacement assays have been used to identify ligands that can inhibit the Rev–RRE interaction; however, the small fluorescence indicators cannot fully replace the Rev peptide or protein. As a result, a single rhodamine B labeled Rev (RB-Rev) model peptide was utilized in this study to develop a direct and efficient Rev–RRE inhibitor screening model. Due to photon-induced electron transfer quenching of the tryptophan residue on the RB fluorophore, the fluorescence of RB in Rev was weakened and could be dramatically reactivated by interaction with RRE RNA in ammonium acetate buffer (approximately six times). The interaction could reduce the electron transfer between tryptophan and RB, and RRE could also increase RB fluorescence. The inhibitor screening model was evaluated using three known positive Rev–RRE inhibitors, namely, proflavin, 6-chloro-9-[3-(2-chloroethylamino)propylamino]-2-methoxyacridine (ICR 191), and neomycin, as well as a negative drug, arginine. With the addition of the positive drugs, the fluorescence of the Rev–RRE decreased, indicating the displacement of RB-Rev. This was confirmed using atomic force microscopy (AFM) and the fluorescence was essentially unaffected by the addition of arginine. The results demonstrated that RB-Rev can be used as a fluorescent probe for recognizing small ligands that target RRE RNA. The Rev–RRE inhibitor screening model offers a novel approach to evaluating and identifying long-acting Rev inhibitors.

Currently, density determination method which is based on the density verification of the liquid is the most popular method for volume of weights measurement. A novel set of apparatus combined with automatic measuring devices and weighing instruments for weight the volume measurement is proposed in this paper. The mechanical structure of the device is optimized. For example, the rod structure of the suspension mechanism avoids the eccentric load error caused by the eccentricity of the lower hook and improves the measurement accuracy. The bubble removal device is added to reduce the error caused by the bubble adhering to the surface of the weight when the weight is immersed in the liquid. After weighing, turn on the drying function to quickly remove the residual liquid on the weight surface.

Interactions between organic matter (OM) and metals in soils are important natural mechanisms that can mitigate metal bioaccumulation in terrestrial environments. A primary source of OM in soils is straw return, accounting for more than 65% of OM input. Straw-OM has long been believed to reduce metal bioaccumulation, e.g., by immobilizing metals in soils. However, there is growing evidence that straw return could possibly enhance bioavailability and thus risks (i.e., food safety) of some metals in crops, including Cd, Hg, and As. Poor understanding of straw return-induced increases in metal bioavailability would add uncertainty in assessing or mitigating risks of metals in contaminated farming soils. Here, 863 pieces of literature (2000–2019) that reported the effects of straw return on metal bioavailability and bioaccumulation were reviewed. Mechanisms responsible for the increased metal mobility and bioavailability under straw return are summarized, including the effects of dissolution, complexation, and methylation. Effects of straw return on the physiology and the absorption of metals in plants is also discussed (i.e., physiological effect). These mechanisms are then used to explain the observed increases in the mobility, bioavailability, and bioaccumulation of Cd, Hg, and As under straw amendment. Information summarized in this study highlights the importance to re-consider the current straw return policy, particularly in metal-contaminated farmlands.

This paper presents a minimal-communication control scheme for series-parallel microgrids to achieve power-sharing and frequency synchronization. The proposed method involves the first distributed generators (DGs) in each string exchanging information with its neighbors using low bandwidth communication to reach a consensus. The other DGs achieve convergence through droop or inverse droop control in a communication-free manner. The proposed control scheme offers several key advantages: 1) Only the first DGs in each string exchange information using low bandwidth communication, while other DGs operate in a decentralized manner. The proposed method is a minimal communication approach. 2) The frequency synchronization is obtained under RL and RC loads. 3) Precise power sharing is achieved by regulating the output voltage amplitudes. Meanwhile, the load voltage quality is guaranteed. Furthermore, the stability analysis based on the root locus method has been demonstrated. Finally, simulations have validated the feasibility of the proposed approach.

The simulation and prediction of landscape patterns can provide a reference for the formulation of ecological space security policies and management and control measures. Therefore, it is necessary to use objective and accurate scientific methods to make accurate simulation predictions. In this study, the quantitative prediction of the Markov model is combined with the advantages of the space-time simulation of the CA model, and the artificial neural network (ANN) module is used for calculation and coupling correction. The Kappa coefficient and the FoM (figure of merit) index are used to test the simulation accuracy. Based on this process, the changes of the landscape pattern in Mudanjiang City at three time points in 2000, 2010 and 2020 were analyzed, and the simulation prediction was made based on this. The experimental results show that the CA-Markov model using the ANN module for coupling correction can be tested for accuracy in the study area, and its Kappa coefficient is 0.834 and the FoM index is 0.001. The model meets the requirements of the landscape pattern for the accuracy of simulation and prediction, and the prediction and analysis of the study area is carried out, and the accurate prediction results are obtained.The results of the study were: Looking at the change in landscape pattern over the 20 years from 2000 to 2020, significant changes occurred in the areas of arable land and artificial surface. The total area of arable land decreased by nearly 130 km2, while the area of artificial surface (i.e., built-up land) increased by about 167 km2. The forest area initially decreased and then increased, with an overall increase of approximately 56 km2, while the water and grassland areas first increased and then decreased. In terms of spatial distribution, the changes in agricultural and forest land are mainly concentrated in the central area where urban development is intensive and in the northern forest area. The results of this study are quite important for policy formulation, according to which it was found that human activities, especially urbanization, have led to a decrease in the area of forested land, and therefore the implementation of the natural forest protection policy can lead to a sustained increase in the area of forested land.

Objective: The Family Integrated Care (FICare) model improves outcomes for preterm infants and parents compared with family-centered care (FCC). FICare with mobile technology (mFICare) may improve uptake and impact. Research on FICare in the United States (US) is scarce and little is known about parents' experience. Methods: We conducted qualitative interviews with nine parents, exploring their NICU experiences, participation in and perceptions of the mFICare program. A directed content analysis approach was used, and common themes were derived from the data. Results: Overall, parents had positive NICU experiences and found mFICare helpful in meeting three common parenting priorities: actively caring for their infant, learning how to care for their infant, and learning about the clinical status of their infant. They described alignment and misalignment with mFICare components relative to their personal parenting priorities and offered suggestions for improvement. Nurses were noted to play key roles in providing or facilitating parent support and encouragement to participate in mFICare and parenting activities. Conclusion: The mFICare program showed potential for parental acceptance and participation in US NICUs. Innovation: The mFICare model is an innovation in neonatal care that can advance the consistent delivery of NICU family-centered care planning and caregiving.Clinical Trial Registration: NCT03418870 01/02/2018.

Considering the power generation cost and bus voltage quality, a distributed economic optimization control strategy and a novel bus voltage estimation method is proposed for the multi-bus low-voltage AC microgrid (MG). Based on the distributed consistency protocol, a novel distributed bus voltage estimator (DBVE), which uses the currents, voltages and the line impendence angle information of local and neighbor DGs, is presented to recover each bus voltage of the system precisely. Meanwhile, a modified distributed incremental cost rate (ICR) consistency protocol is proposed to obtain the global optimal dynamic economic dispatch (ED) of system under the capacity constraints by switching seamlessly the control strategy of each dispatchable DG (DDG) between constant power control and distributed ED strategy. Moreover, the active power is dispatched to minimize the total power generation cost considering the capacity limitation of each DG and balance between supply and demand, and the apparent power is shared among DGs according to the maximum active power rate of all DGs. To this end, a small-signal stability analysis is given to obtain the feasible regions for the control parameters. Finally, several simulation cases are conducted under various working conditions to verified the effectiveness and feasibility of the proposed method.

Currently, stem cells are a prominent focus of regenerative engineering research. However, due to the limitations of commonly used stem cell sources, their application in therapy is often restricted to the experimental stage and constrained by ethical considerations. In contrast, urine-derived stem cells (USCs) offer promising advantages for clinical trials and applications. The noninvasive nature of the collection process allows for repeated retrieval within a short period, making it a more feasible option. Moreover, studies have shown that USCs have a protective effect on organs, promoting vascular regeneration, inhibiting oxidative stress, and reducing inflammation in various acute and chronic organ dysfunctions. The application of USCs has also been enhanced by advancements in biomaterials technology, enabling better targeting and controlled release capabilities. This review aims to summarize the current state of research on USCs, providing insights for future applications in basic and clinical settings.

Vehicle-to-Vehicle (V2V) energy trading has emerged as a promising scheme to relieve the load imposed on the grid without intermediaries. The blockchain has always been regarded as the most potential solution for addressing the security and privacy issues of the Internet of Electric Vehicles (IoEV). The consensus mechanism is the core of the blockchain, it determines the security, efficiency, and scalability of the system. However, consensus mechanisms currently employed in V2V energy trading are traditional algorithms, which are unsuitable for the IoEV due to their high computational power and communication overhead. Therefore, we are motivated to propose a Block Alliance Consensus (BAC) mechanism based on Hashgraph. BAC can maintain the high throughput of the Hashgraph, and it solves the problem that the Hashgraph cannot support the dynamic addition and deletion of nodes if it is directly applied to V2V energy trading. We utilize the sharding technique, and each shard generates a consortium blockchain in accordance with the characteristic of the IoEV. The centralized component is retained to ensure macroeconomic control by state and local governments. We design a cryptography-based leader election combined with a reputation incentive mechanism to fairly elect centralized leader committee and motivate honest electric vehicles (EVs). We implement the BAC consensus and V2V energy trading blockchain (ETB) on the Hyperledger Fabric. The performance and practicality of BAC and the V2V ETB are verified through experiments.

ABSTRACT: Objectives: Emergence of multidrug-resistant (MDR) Salmonella enterica serovar Indiana has raised global concern. Mobile genetic elements (MGEs) play vital roles in accelerating the dissemination of resistance genes in bacteria communities. The study aims to improve our understanding of the underlying resistance mechanisms and characterize the MGEs in a MDR S. Indiana isolate. Methods: Here, we report the characteristics of a MDR pathogenic S. Indiana isolate. The antimicrobial susceptibility pattern of S. Indiana QT6365 was determined. The genomic structure of the chromosome and the plasmid, serotype, and multi-locus sequence type were analysed by whole genome sequencing. The circular form derived from IS26-flanked transposon was confirmed by reverse polymerase chain reaction and sequencing. Results: S. Indiana QT6365 exhibited resistance to all tested antimicrobials except for aztreonam, amikacin, polymyxin, and tigecycline, was defined as MDR, and belonged to ST17. S. Indiana QT6365 was closely related with food resource S. Indiana C629 with similar resistance gene profiles. Multiple resistance genes are mainly carried by a novel transposon Tn7540 located on the chromosome and an IncHI2/HI2A/N plasmid. Sequence analysis and the formed circular intermediate suggested Tn7540 might be generated through homologous recombination by IS26-bounded translocatable units (IS26-fosA-IS26-intI1-dfrA12-aadA2-sul1-ISCR1-blaNDM-9-IS26). Conclusions: To the best of our knowledge, this is the first report of the novel chromosomal transposon possessing blaNDM-9 and fosA3 in S. Indiana isolated from human specimen, which might facilitate the dissemination of resistance genes and should arouse serious awareness.

Background: Recurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by Candida in RVVC has been recently questioned. This study aimed to elucidate the fundamental growth modes of Candida in the vagina of patients with RVVC or sporadic vulvovaginal candidiasis (VVC) and to assess their roles in the persistence of RVVC. Methods: Vaginal tissues were sampled from twelve patients clinically and microbiologically diagnosed as RVVC or VVC at a post-antifungal-treatment and asymptomatic period. High-resolution scanning electron microscopy, fluorescence in situ hybridization in combination with Candida-specific 18S rRNA probes and viable fungal burden were used to qualitatively and quantitatively evaluate Candida growth in the human vagina. The presence of Candida biofilm extracellular polymeric substances was examined using confocal laser scanning microscopy and biopsy sections pre-stained with Concanavalin A. Histopathological analysis was carried out on infected vaginal tissues stained with hematoxylin and eosin. Lastly, the susceptibility of epithelium-associated Candida biofilms to fluconazole at the peak serum concentration was evaluated. Results: Candida species grew on the vaginal epithelium of RVVC patients as morphologically disparate biofilms including monolayers, microcolonies, and macro-colonies, in addition to sporadic adherent cells. Candida biofilm growth on the vaginal epithelium was associated with mild lymphocytic infiltration of the vaginal mucosa. These epithelium-based Candida biofilms presented an important characteristic contributing to the persistence of RVVC that is the high tolerance to fluconazole. Conclusions: In summary, our study provides direct evidence to support the presence of Candida biofilms in RVVC and an important role of biofilm formation in disease persistence.

Cement mortar is the primary choice for construction due to its widespread usage. However, certain applications demand high-performance cement mortar. In this pioneering study, we explore using agriculture waste products, industrial by-products, and naturally occurring kaolinite clay as potential additives in composite cement. Our research aims to assess these materials' physical and mechanical attributes to ascertain their efficacy in elevating cement performance. To achieve this, we replaced 20% of the cement in the composite with silica-fume and metakaolin, following a precise mix design fraction of 1:1 (binding materials: sand) for the mortar composites. We successfully identified the optimum combination of metakaolin and silica fume through systematic experimentation that maximizes compression strength. Subsequently, we introduced various proportions of coir fibers (ranging from 3% to 15% by weight) into the cement composite to enhance its structural support capabilities. We carefully calibrated the ratio of the water-to-binding material (ranging from 0.35 to 0.6) to maintain the workability of the cement mixtures. Next, we subjected the cement composites to meticulous curing in water for 7 days, 14 days, and 28 days, respectively, to observe their performance over time. Our comprehensive study encompassed the investigation of critical parameters, including moisture content, density, and water absorption, as well as essential mechanical properties such as compressive strength and modulus of rupture. A total of 270 specimens underwent rigorous testing, yielding compelling results. The composite featuring a combination of 10% silica fume, 10% metakaolin, and 6% coconut fibers showcased superior mechanical and physical properties. SEM and EDX studies also showed dense and packed microstructure of mortar samples. These findings showcase the remarkable potential of this specific composite composition as an environmentally conscious and sustainable alternative to enhance cement performance in construction applications. This research advances eco-friendly construction practices by harnessing the strength of waste-derived materials and naturally occurring resources, supporting a more sustainable and resilient approach to infrastructure development.

Adoptive cell therapies (ACT) based on chimeric antigen receptor (CAR)-modified immune cells have made great progress with six CAR-T cell products approved by the U.S. FDA for hematological malignancies. Compared with CAR-T cells, CAR-NK cells have attracted increasing attention owing to their multiple killing mechanisms, higher safety profile, and broad sources. Induced pluripotent stem cell (iPSC)-derived NK (iPSC-NK) cells possess a mature phenotype and potent cytolytic activity, and can provide a homogeneous population of CAR-NK cells that can be expanded to clinical scale. Thus, iPSC-derived CAR-NK (CAR-iNK) cells could be used as a standardized and “off-the-shelf” product for cancer immunotherapy. In this review, we summarize the current status of the manufacturing techniques, genetic modification strategies, preclinical and clinical evidence of CAR-iNK cells, and discuss the challenges and future prospects of CAR-iNK cell therapy as a novel cellular immunotherapy in cancer.

Confronting the challenge of persistent mutations of SARS-CoV-2, researchers have turned to deep learning methods to predict the mutated structures of spike proteins and to hypothesize potential changes in their structures and drug efficacies. However, limited works are focused on the surface learning of spike proteins even though their biological functions are usually defined by the geometric and chemical features of 3D molecular surfaces. In addition, the current used geometric deep learning methods are based on mesh representations of proteins to identify potential binding targets for drugs. However, the use of meshes has limitations and is not applicable for many important tasks in molecular biology. To address these limitations, we adopt the differentiable molecular surface interaction fingerprinting (dMaSIF) method which is based on the 3D point clouds and a novel efficient geometric convolutional layer to fast predict the interaction sites on the protein surface. The different binding site patterns for Delta, Omicron and its subvariants are clearly visualized. We find that Delta and Omicron show the similar surface binding patterns while BA.2, BA.2.13, BA.3 and BA.4 present similar ones. BA.4 possesses higher positive interaction site ratio than the others which may account for its higher transmission and infection among humans. In addition, the positive interaction site ratios of BA.2, BA.2.13, BA.3 are higher than Delta and Omicron, which are accordant with their transmission and infection rates. Hopefully our work offers a new effective route to analyze the protein-protein interaction for the SARS-CoV-2 variants.

Three-dimensional (3D) building structures are vital to understanding urban dynamics. Monocular remote sensing imagery is a cost-effective data source for large-scale building height retrieval when compared to LiDAR data and multi-view imagery. Existing methods learn building footprints and height maps per pixel via either a multi-task network or two separate networks, however, failing to consider the information of neighboring pixels that belong to the identical building. Therefore, we propose learning a novel representation for 3D buildings, namely 3D centripetal shifts, a unified representation of individual building instances. Our method is termed as 3DCentripetalNet and learns the 3D centripetal shift representation that incorporates planar and vertical structures of buildings. Afterward, a decoupling module is devised to learn building corner points. Finally, a 3D modeling module is designed to retrieve building height from the learned 3D centripetal shift map and corner points. We investigate the proposed 3DCentripetalNet on two datasets with different spatial resolutions, i.e., the ISPRS Vaihingen dataset (9 cm/pixel) and the Urban 3D dataset (50 cm/pixel). Experimental results suggest that 3DCentripetalNet is able to preserve sharp building boundaries, largely alleviate false detections, and significantly outperform other competitors. Thus, we believe that 3DCentripetalNet is a robust solution for the task of building height retrieval from monocular imagery.

Objective: Disuse osteoporosis is a major type of bone loss disease characterized by regional bone loss and microstructure alterations. The condition is induced by a marked decrease in weight bearing over time, which usually occurs due to limb immobilization, therapeutic bed rest or space flight. To date, the most commonly used mouse model of disuse osteoporosis is constructed using the classical tail suspension method, which causes tail injury, movement inconvenience and mental stress. This study aimed to propose a noninvasive and effective method for the establishment of a mouse model of disuse osteoporosis and compared this method with the tail suspension method. Methods: 3D printing technology was applied to construct a movable unloading device. A movable noninvasive 3D-printed unloading device (3D-ULD) was used to unload the hindlimbs of the mice. The bone microstructure and bone volume of unloaded femurs were analysed through micro-CT and H&E staining, and von Kossa staining was performed for the detection of bone mineralization in the femurs. TRAP staining, IHC-CTSK and Q-PCR were performed for evaluation of the bone resorption ability, and double labelling, IHC-DMP1, ALP staining and Q-PCR assays were conducted to assess the osteogenic ability. The mechanical properties of disused bone were detected using the three-point bending test. The body, thymus and spleen weights of the mice were recorded, and the serum corticosterone level of the mice was assayed by enzyme-linked immunosorbent assay (ELISA). Results: The micro-CT results showed significant trabecular bone loss, and 3D-ULD induced cortical bone loss in disused femurs as well as a decrease in the bone mineral density in the unloaded mice. TRAP staining and IHC-CTSK staining results indicated increases in the osteoclast number per bone perimeter (Oc.N/B.Pm) and the osteoclast surface per bone surface (Oc.S/BS) in the unloaded mice. The Ctsk, Trap and Mmp9 expression levels were significantly increased in the unloaded mice. Decreases in the ratio of the mineral surface to bone surface (MS/BS), mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS) were found in unloaded mice in the 3D-ULD by double labelling. The IHC-DMP1 and ALP staining results showed decreases in the osteoblast number per bone perimeter (Ob.N/B.Pm) and osteoblast surface per bone surface (Ob. S/BS) in the mice unloaded in the 3D-ULD, and these mice also showed decreased Runx2, Alp and Dmp1 expression levels. Three-point bending test results showed that the mechanical properties were attenuated in the disused femurs of the unloaded mice. Less skin rupture and rare alterations in the thymus and spleen weights were found in the unloaded mice in the 3D-ULD. The ELISA results indicated the serum corticosterone level of the mice unloaded in the 3D-ULD was significantly lower than that of mice suspended by their tail. Conclusion: This new disuse osteoporosis mouse model based on 3D-ULD could induce effective disuse bone loss with significantly alleviated side effects. Translational potential of this article: This study proposes a new disuse osteoporosis mouse model based on 3D-ULD that can be used to better understand disuse bone loss in the future.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has led to a global pandemic. Deep learning (DL) technology and molecular dynamics (MD) simulation are two mainstream computational approaches to investigate the geometric, chemical and structural features of protein and guide the relevant drug design. Despite a large amount of research papers focusing on drug design for SARS-COV-2 using DL architectures, it remains unclear how the binding energy of the protein-protein/ligand complex dynamically evolves which is also vital for drug development. In addition, traditional deep neural networks usually have obvious deficiencies in predicting the interaction sites as protein conformation changes. In this review, we introduce the latest progresses of the DL and DL-based MD simulation approaches in structure-based drug design (SBDD) for SARS-CoV-2 which could address the problems of protein structure and binding prediction, drug virtual screening, molecular docking and complex evolution. Furthermore, the current challenges and future directions of DL-based MD simulation for SBDD are also discussed.

Summary: Oral and maxillofacial organoids, as three-dimensional study models of organs, have attracted increasing attention in tissue regeneration and disease modeling. However, traditional strategies for organoid construction still fail to precisely recapitulate the key characteristics of real organs, due to the difficulty in controlling the self-organization of cells in vitro. This review aims to summarize the recent progress of novel approaches to engineering oral and maxillofacial organoids. First, we introduced the necessary components and their roles in forming oral and maxillofacial organoids. Besides, we discussed cutting-edge technology in advancing the architecture and function of organoids, especially focusing on oral and maxillofacial tissue regeneration via novel strategy with designed cell-signal scaffold compounds. Finally, current limitations and future prospects of oral and maxillofacial organoids were represented to provide guidance for further disciplinary progression and clinical application to achieve organ regeneration.

Objectives: This study aimed to evaluate the performance of the NitroSpeed-Carba NP test for detecting carbapenemases in the clinical strains of Enterobacterales and Pseudomonas aeruginosa (P. aeruginosa), and analyze its advantages and limitations. Methods: The antimicrobial susceptibility tests were performed according to the agar dilution method. Using the modified carbapenemase inactivation method (mCIM), polymerase chain reaction (PCR), and sequencing, the production of carbapenemase and the prevalence of genes were studied. The NitroSpeed-Carba NP test was performed to detect different types of carbapenemases in Enterobacterales and P. aeruginosa. The results of PCR and sequencing were used as the gold standard. Results: Among 144 carbapenemase-producing and 54 carbapenemase-negative strains of Enterobacterales and P. aeruginosa, the NitroSpeed-Carba NP test correctly detected 143 of 144 carbapenemase producers and 51 of 54 non-carbapenemase producers. Moreover, the sensitivity and specificity of all tested isolates were 99.31% and 94.44%, respectively (99.28% and 92.86% for Enterobacterales; 100% and 100% for P. aeruginosa). The sensitivity was 100% for class A (56 of 56), 100% for class B (60 of 60), and 100% for class D (27 of 27). Conclusions: The results suggest that NitroSpeed-Carba NP test is a simple and valuable assay that could be used as a rapid and stable detection method to identify the carbapenemases in Enterobacterales and P. aeruginosa strains.

Objectives: Triclosan is usually employed as a disinfectant in a wide range of medical and consumer care products, which may have imposed a selective pressure on bacteria. This study was designed to evaluate the resistance mechanisms of triclosan and molecular epidemiology of triclosan-resistant isolates of Acinetobacter baumannii in Wenzhou, China. Methods: A collection of 626 A. baumannii were isolated from the First Affiliated Hospital of Wenzhou Medical University during 2016-2017 and antimicrobial susceptibility testing of these isolates were performed via agar dilution method. Molecular mechanisms of triclosan resistance, including the existence of mutations in reductase (FabI) were investigated by PCR and sequencing. Furthermore, quantitative RT-PCR was conducted to evaluate the expression levels of the fabI gene and efflux pump genes (adeB, adeG, adeJ, abeM, amvA and abeS) at normal condition and sub-inhibitory concentration of triclosan, and the epidemiological characteristics were analyzed by PFGE and MLST. Results: 2.7% (17/626) of A. baumannii exhibited resistance to triclosan. The FabI mutation Gly95Ser was found in one triclosan resistant strain. The expression of fabI and adeB gene were significant difference between triclosan-resistant and susceptible strains (P

Objective: To characterize the evolutionary pathways of tigecycline (TGC) resistance and alterations in the biological characteristics of hospital-derived Staphylococcus aureus isolates under selective pressure. Methods: Three clinical S. aureus strains and one standard S. aureus strain, ATCC 29213, were used for the in vitro selection of TGC-resistant S. aureus variants with gradient concentrations of TGC. Changes in drug resistance and genetic alterations in resistance-related genes (operon mepRAB and rpsJ) in mutant strains were determined. The efflux inhibitor assay for MepA and the fitness cost, determined by comparing the growth and virulence of parental and mutant strains, were also investigated. Results: Mutants induced in vitro showed a 64- to 128-fold increase in the minimum inhibitory concentration (MIC) of TGC. Substitution mutations were detected in the transcriptional repressor mepR and the efflux pump gene mepA. A K57M amino acid substitution occurred in the ribosomal S10 protein-encoding gene rpsJ. The MICs of TGC in the final mutants were significantly decreased in the presence of efflux pump inhibitors. It was worth noting that growth was unaffected by TGC resistance selection in vitro, with the exception of one strain, and the MICs of other antibiotics and virulence were also unaffected. Conclusions: The evolution of TGC resistance in S. aureus in vitro is associated with a loss-of-function mutation in the efflux pump transcriptional repressor mepR and a missense mutation in the efflux pump-encoding gene mepA. Our work further validated the resistance mechanisms of S. aureus to TGC and reported previously undiscovered mutations.

Piezoresponse Force Spectroscopy (PFS) is a powerful technique widely used for measuring the nanoscale electromechanical coupling of the ferro-/piezo-electric materials. However, it is found that certain non-ferroelectric materials can also generate the “hysteresis-loop-like” responses from the PFS measurements due to many other factors such as electrostatic effects. This work therefore studies the signal of the contact resonance frequency during the PFS measurements. By comparing the results from ferroelectric and non-ferroelectric materials, it is found there are distinct differences between these two types of materials in the variation of the contact resonance frequency during the PFS measurements. A momentary and sharp increase of the contact resonance frequency occurs when the domain is switched by applying the DC bias, which can be regarded as a unique characteristic for the ferroelectric materials. After analyzing the reliability and mechanism of this method, it is proposed that the contact resonance frequency variation at the coercive bias is capable to differentiate the electromechanical responses of the ferroelectric and non-ferroelectric materials during the PFS measurements. Keywords: Ferroelectricity, Piezoresponse force spectroscopy, Contact resonance frequency, Dual AC resonance tracking, Domain switching, Damping harmonic oscillator model

Functional MRI (fMRI) is extremely challenging to perform in subjects who move because subject motion disrupts blood oxygenation level dependent (BOLD) signal measurement. It has become common to use retrospective framewise motion detection and censoring in fMRI studies to eliminate artifacts arising from motion. Data censoring results in significant loss of data and statistical power unless the data acquisition is extended to acquire more data not corrupted by motion. Acquiring more data than is necessary leads to longer than necessary scan duration, which is more expensive and may lead to additional subject non-compliance. Therefore, it is well established that real-time prospective motion monitoring is crucial to ensure data quality and reduce imaging costs. In addition, real-time monitoring of motion allows for feedback to the operator and the subject during the acquisition, to enable intervention to reduce the subject motion. The most widely used form of motion monitoring for fMRI is based on volume-to-volume registration (VVR), which quantifies motion as the misalignment between subsequent volumes. However, motion is not constrained to occur only at the boundaries of volume acquisition, but instead may occur at any time. Consequently, each slice of an fMRI acquisition may be displaced by motion, and assessment of whole volume to volume motion may be insensitive to both intra-volume and inter-volume motion that is revealed by displacement of the slices. We developed the first slice-by-slice self-navigated motion monitoring system for fMRI by developing a real-time slice-to-volume registration (SVR) algorithm. Our real-time SVR algorithm, which is the core of the system, uses a local image patch-based matching criterion along with a Levenberg-Marquardt optimizer, all accelerated via symmetric multi-processing, with interleaved and simultaneous multi-slice acquisition schemes. Extensive experimental results on real motion data demonstrated that our fast motion monitoring system, named Slice Localization Integrated MRI Monitoring (SLIMM), provides more accurate motion measurements than a VVR based approach. Therefore, SLIMM offers improved online motion monitoring which is particularly important in fMRI for challenging patient populations. Real-time motion monitoring is crucial for online data quality control and assurance, for enabling feedback to the subject and the operator to act to mitigate motion, and in adaptive acquisition strategies that aim to ensure enough data of sufficient quality is acquired without acquiring excess data.

Background/Purpose: Only limited information is available about the detailed characteristics of qnrD, a plasmid-mediated quinolone resistance (PMQR) gene. This study aimed to understand the distribution of qnrD and the characterization of qnrD-carrying plasmids in Proteeae. Methods: The distribution of qnrD genes was investigated by polymerase chain reaction (PCR) amplification in 203 consecutive nonduplicate clinical isolates of Proteeae collected from inpatients at the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. The minimum inhibitory concentrations (MICs) of antibiotics were measured by agar dilution method and other PMQR determinants were also determined by PCR. qnrD was positioned via Southern hybridization and the transferability of qnrD-carrying plasmids was achieved by conjugation experiment. The genetic environment of qnrD was investigated by sequencing, and chromosomal polymorphism for qnrD-positive strains was analyzed by pulsed-field gel electrophoresis (PFGE). Results: Forty strains carried qnrD, showing decreased fluoroquinolone susceptibility or low-level fluoroquinolone resistance. qnrD was encoded on the plasmid of about 2.7 kb or 5.2 kb in length, which cannot be transferred by liquid conjugation or filter mating, but can be successfully transferred by transduction. The transformants showed 62.5–300-fold increases in the MICs of quinolones compared with the recipient. The plasmids carrying qnrD showed a high similarity with that of Providencia spp. and Proteus vulgaris. PFGE analysis demonstrated that these isolates were divergent and not clone related. Conclusion: qnrD could have originated from Proteeae or presented in these bacteria as a reservoir; furthermore, qnrD could be transferred and spread within the same or across different bacterial species if the plasmids acquired mobile elements under antimicrobial selective pressures.

Major depressive disorder (MDD) and bipolar disorder (BD) are severe psychiatric diseases with overlapping symptomatology. Although previous studies reported abnormal brain structures in MDD or BD patients, the disorder-specific underlying neural mechanisms remain poorly understood. The purpose of this study was to investigate the whole-brain gray matter morphological patterns in unmedicated patients with MDD or BD and to identify the shared and disease-specific brain morphological alterations in these two disorders. We acquired high-resolution brain structural MRI data from a sample of 36 MDD patients, 32 BD patients, and 30 healthy controls. Using FreeSurfer, we estimated their brain cortical thickness (CT) and compared between-group difference in multiple locations across the continuous cortical surface. Compared to the healthy controls, both the MDD and BD patient groups showed significantly reduced CT in the left inferior temporal cortex (ITC). However, compared to the MDD patients, the BD patients showed a significantly thinner CT in the left rostral middle frontal region. In addition, compared to the healthy controls, the BD patients displayed thinner CT in the left ITC, left frontal pole (FPO), left superior frontal, right lateral occipital, right pars triangularis (PTRI) and right lateral orbitofrontal regions. Further analysis revealed a significantly positive correlation between the mean CT in the left FPO and the onset age, but a negative correlation between the mean CT in the right PTRI and the number of episodes, in the BD patients. Our findings revealed that the BD and MDD patients had variations in CT that were in common, but many more that were distinct, suggesting potential differences in their neural mechanisms.

The vacuolar proton pump ATPase (V-H+-ATPase), which is a multi-subunit membrane protein complex, plays a major role in the activation of ion and nutrient transport and has been suggested to be involved in several physiological processes, such as cell expansion and salt tolerance. In this study, three genes encoding V-H+-ATPase subunits B (ScVHA-B, GenBank: JF826506), C (ScVHA-C, GenBank: JF826507) and H (ScVHA-H, GenBank: JF826508) were isolated from the halophyte Suaeda corniculata. The transcript levels of ScVHA-B, ScVHA-C and ScVHA-H were increased by salt, drought and saline-alkali treatments. V-H+-ATPase activity was also examined under salt, drought and saline-alkali stresses. The results showed that V-H+-ATPase activity was correlated with salt, drought and saline-alkali stress. Furthermore, V-H+-ATPase subunits B, C and H (ScVHA-B, ScVHA-C and ScVHA-H) from S. corniculata were introduced separately into the alfalfa genome. The transgenic alfalfa was verified by Southern and Northern blot analysis. During salt and saline-alkali stresses, transgenic lines carrying the B, C and H subunits had higher germination rates than the wild type (WT). More free proline, higher superoxide dismutase (SOD) activity and lower malondialdehyde (MDA) levels were detected in the transgenic plants under salt and saline-alkali treatments. Moreover, the ScVHA-B transgenic lines showed greater tolerance to salt and saline-alkali stresses than the WT. These results suggest that overexpression of ScVHA-B, ScVHA-C and ScVHA-H improves tolerance to salt and saline-alkali stresses in transgenic alfalfa.