Analysis of multidrug-resistant determinants of clinically isolated Acinetobacter baumannii CYZ via whole genome sequencing.

Acinetobacter baumannii is a multidrug-resistant coccobacillus responsible for severe nosocomial infectious diseases. This study mainly focuses on investigating the antimicrobial resistance features of a clinically isolated strain (A. baumannii CYZ) using the PacBio Sequel II sequencing platform. The chromosomal size of A. baumannii CYZ is 3,960,760 bp, which contains a total of 3803 genes with a G + C content of 39.06%. Functional analysis performed using the Clusters of Orthologous Groups of Proteins (COGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, as well as the Comprehensive Antibiotic Resistance Database (CARD) revealed a complicated set of antimicrobial resistance determinants in the genome of A. baumannii CYZ, which were mainly classified into multidrug efflux pumps and transport systems, ß-lactamase relative and penicillin-binding proteins, aminoglycoside modification enzymes, alternation of antibiotic target sites, lipopolysaccharide relative, and other mechanisms. A total of 35 antibiotics were tested for the antimicrobial susceptibility of A. baumannii CYZ, and the organism exhibited a stronger antimicrobial resistance ability. The phylogenetic relationship indicated that A. baumannii CYZ has high homology with A. baumannii ATCC 17978; however, the former also exhibited its specific genome characteristics. Our research results give insight into the genetic antimicrobial-resistant features of A. baumannii CYZ as well as provide a genetic basis for the further study of the phenotype.

Modified biochar/humic substance/fertiliser compound soil conditioner for highly efficient improvement of soil fertility and heavy metals remediation in acidic soils.

Fertile and uncontaminated soil with appropriate pH is crucial in terms of the agricultural sustainable development. Herein, a compound soil conditioner containing chitosan modified straw biochar (CBC), kitchen waste compost product-derived humic substance (HS), NPK compound fertiliser (NPK-CF) was prepared to simultaneously adjust acidic soil pH, improve fertility, and immobilize heavy metal. The results exhibited that the best Pb and NH4+ adsorption performance was obtained in CBC with chitosan:biochar of 1:5. Then, the acid soil pH was improved from 5.03 to 6.66 in the presence of CBC/HS (5:5) with 3% addition weight (the mass ratio of conditioner to soil). Meanwhile, compared with the control, the contents of organic matter, available nitrogen, and available phosphorus significantly increased by 52.4%, 92.6%, and 136.3%, respectively. Moreover, Pb was highly efficient immobilised by CBC, and the concentration of Pb in the soil was decreased by 55.2%. The optimal growth trend of ryegrass was obtained in the presence of 3% addition weight (the mass ratio of conditioner to soil) CBC/HS (CBC:HS = 5:5) combined with 60% of the recommended NPK-CF application weight, which was mainly contributed by the improvement of the soil microbial abundance and community structure diversity. The addition of CBC/HS could effectively reduce the addition of NPK-CF and contribute to simultaneous controlling nitrogen loss, releasing phosphorus, immobilising Pb, adjusting pH, improving soil quality and controlling nonpoint pollution.

Assessment of morphometry of pulmonary acini in mouse lungs by nondestructive imaging using multiscale microcomputed tomography.

Establishing the 3D architecture and morphometry of the intact pulmonary acinus is an essential step toward a more complete understanding of the relationship of lung structure and function. We combined a special fixation method with a unique volumetric nondestructive imaging technique and image processing tools to separate individual acini in the mouse lung. Interior scans of the parenchyma at a resolution of 2 µm enabled the reconstruction and quantitative study of whole acini by image analysis and stereologic methods, yielding data characterizing the 3D morphometry of the pulmonary acinus. The 3D reconstructions compared well with the architecture of silicon rubber casts of mouse acini. The image-based segmentation of individual acini allowed the computation of acinar volume and surface area, as well as estimation of the number of alveoli per acinus using stereologic methods. The acinar morphometry of male C57BL/6 mice age 12 wk and 91 wk was compared. Significant increases in all parameters as a function of age suggest a continuous change of the lung morphometry, with an increase in alveoli beyond what has been previously viewed as the maturation phase of the animals. Our image analysis methods open up opportunities for defining and quantitatively assessing the acinar structure in healthy and diseased lungs. The methods applied here to mice can be adjusted for the study of similarly prepared human lungs.

Finite-Time Event-Triggered Output Consensus of Heterogeneous Fractional-Order Multiagent Systems With Intermittent Communication.

The finite-time output consensus (FTOC) issue of heterogeneous fractional-order multiagent systems (HFO-MASs) is investigated in this article. First, a new principle of finite-time convergence for absolutely continuous functions is developed if a fractional derivative inequality is satisfied. Next, in order to remove the assumption that the leader's system matrix is known to all agents in previous studies, a distributed adaptive finite-time observer is designed, which can estimate not only the leader's state but also the leader's system matrix. Then, a novel finite-time event-triggered compensator with intermittent communication is constructed to estimate the leader's state by introducing a dynamic threshold for a novel triggering function. In this case, the high frequency triggering is restrained and the triggering number is significantly reduced. The Zeno behavior does not exist by choosing parameters appropriately. In addition, two finite-time control strategies are constructed based on the above distributed observer and event-triggered compensator, respectively, to achieve output consensus in finite time. The feasibility of the proposed method is ensured by the comprehensive theoretical demonstration of the finite-time consensus stability and the analysis of the Zeno behavior. Finally, the examples are given to demonstrate the conclusion.

Neural-Network-Based Finite-Time Bipartite Containment Control for Fractional-Order Multi-Agent Systems.

This article focuses on the adaptive bipartite containment control problem for the nonaffine fractional-order multi-agent systems (FOMASs) with disturbances and completely unknown high-order dynamics. Different from the existing finite-time theory of fractional-order system, a lemma is developed that can be applied to actualize the aim of finite-time bipartite containment for the considered FOMASs, in which the settling time and convergence accuracy can be estimated. Via applying the mean-value theorem, the difficulty of the controller design generated by the nonaffine nonlinear term is overcome. A neural network (NN) is employed to approximate the ideal input signal instead of the unknown nonaffine function, then a distributed adaptive NN bipartite containment control for the FOMASs is developed under the backstepping structure. It can be proved that the bipartite containment error under the proposed control scheme can achieve finite-time convergence even though the follower agents are subjected to completely unknown dynamic and disturbances. Finally, the feasibility and validity of the obtained results are exhibited by the simulation examples.

Adaptive Bipartite Event-Triggered Time-Varying Output Formation Tracking of Heterogeneous Linear Multi-Agent Systems Under Signed Directed Graph.

This study investigates the adaptive bipartite event-triggered time-varying output formation tracking for heterogeneous linear multi-agent systems (MASs) under signed directed communication topology. Both cooperative communication and antagonistic communication among agents are considered. The fully distributed bipartite compensator based on the novel composite event-triggered transmission mechanism is first put forward to estimate the state of the leader. Compared with the existing methods, our compensator can save communication resources using event-triggered transmission mechanism; is independent of the global information of the network graph; and is applicable for the signed directed graph. With the developed compensator, the distributed control protocol is designed to achieve the time-varying output formation tracking. Moreover, the case that the networked systems subject to external disturbances is also considered. To estimate the state of leader with disturbance, the fully distributed bipartite compensator based on an innovative composite event-triggered mechanism is presented. And the novel distributed control protocol is proposed to address the output formation tracking issue for linear MASs with heterogeneous dynamics and external disturbances. It is shown that the Zeno-behavior can be excluded in both transmission mechanisms. Finally, the effectiveness of the developed control methods is illustrated through three simulation examples.

Fully Distributed Event/Self-Triggered Bipartite Output Formation-Containment Tracking Control for Heterogeneous Multiagent Systems.

This article considers the bipartite time-varying output formation-containment tracking control issue for general linear heterogeneous multiagent systems with multiple nonautonomous leaders, where the full states of agents are not available. Both cooperative interaction and antagonistic interaction between neighboring agents are taken into account. First, an observer is constructed using the output information to observe the state information. Then, based on the information between neighboring agents, an independent asynchronous fully distributed event-triggered bipartite compensator is put forward to estimate the convex hull spanned by the states of multiple leaders. Note that the compensator does not require to use of any global information. Subsequently, a formation-containment tracking control strategy based on the observer and compensator and an algorithm to determine its control parameters are given. The Zeno behavior is further proved to be excluded in any finite time. In addition, a novel self-triggered control strategy based only on the sampled information at triggering instants is also formulated, which avoids continuous communication among agents. Finally, a numerical example is given to validate the effectiveness and performance of the proposed control strategies.

Ferrets: A powerful model of SARS-CoV-2.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social, economic, and health burdens worldwide. Despite considerable efforts to combat coronavirus disease 2019 (COVID-19), various SARS-CoV-2 variants have emerged, and their underlying mechanisms of pathogenicity remain largely unknown. Furthermore, effective therapeutic drugs are still under development. Thus, an ideal animal model is crucial for studying the pathogenesis of COVID-19 and for the preclinical evaluation of vaccines and antivirals against SARS-CoV-2 and variant infections. Currently, several animal models, including mice, hamsters, ferrets, and non-human primates (NHPs), have been established to study COVID-19. Among them, ferrets are naturally susceptible to SARS-CoV-2 infection and are considered suitable for COVID-19 study. Here, we summarize recent developments and application of SARS-CoV-2 ferret models in studies on pathogenesis, therapeutic agents, and vaccines, and provide a perspective on the role of these models in preventing COVID-19 spread.

HBV precore G1896A mutation promotes growth of hepatocellular carcinoma cells by activating ERK/MAPK pathway.

Chronic hepatitis B virus (HBV) infection is one of the leading causes of hepatocellular carcinoma (HCC). The HBV genome is prone to mutate and several variants are closely related to the malignant transformation of liver disease. G1896A mutation (G to A mutation at nucleotide 1896) is one of the most frequently observed mutations in the precore region of HBV, which prevents HBeAg expression and is strongly associated with HCC. However, the mechanisms by which this mutation causes HCC are unclear. Here, we explored the function and molecular mechanisms of the G1896A mutation during HBV-associated HCC. G1896A mutation remarkably enhanced the HBV replication in vitro. Moreover, it increased tumor formation and inhibited apoptosis of hepatoma cells, and decreased the sensitivity of HCC to sorafenib. Mechanistically, the G1896A mutation could activate ERK/MAPK pathway to enhanced sorafenib resistance in HCC cells and augmented cell survival and growth. Collectively, our study demonstrates for the first time that the G1896A mutation has a dual regulatory role in exacerbating HCC severity and sheds some light on the treatment of G1896A mutation-associated HCC patients.

Adaptive Bipartite Fixed-Time Time-Varying Output Formation-Containment Tracking of Heterogeneous Linear Multiagent Systems.

This study investigates the bipartite fixed-time time-varying output formation-containment tracking issue for heterogeneous linear multiagent systems with multiple leaders. Both cooperative communication and antagonistic communication between neighbor agents are taken into account. First, the bipartite fixed-time compensator is put forward to estimate the convex hull of leaders' states. Different from the existing techniques, the proposed compensator has the following three highlights: 1) it is continuous without involving the sign function, and thus, the chattering phenomenon can be avoided; 2) its estimation can be achieved within a fixed time; and 3) the communication between neighbors can not only be cooperative but also be antagonistic. Note that the proposed compensator is dependent on the global information of network topology. To deal with this issue, the fully distributed adaptive bipartite fixed-time compensator is further proposed. It can estimate not only the convex hull of leaders' states but also the leaders' system matrices. Based on the proposed compensators, the distributed controllers are then developed such that the bipartite time-varying output formation-containment tracking can be achieved within a fixed time. Finally, two examples are given to illustrate the feasibility of the main theoretical findings.

Bipartite Fixed-Time Output Consensus of Heterogeneous Linear Multiagent Systems.

In this article, the bipartite fixed-time output consensus problem of heterogeneous linear multiagent systems (MASs) is investigated. First, a distributed bipartite fixed-time observer is proposed, by which the follower can estimate the leader's state. The estimate value is the same as the leader's state in modulus but may not in sign due to the existence of antagonistic interactions between agents. Then, an adaptive bipartite fixed-time observer is further proposed. It is fully distributed without involving any global information. This adaptive bipartite fixed-time observer can estimate not only the leader's system matrix but also the leader's state. Next, distributed nonlinear control laws are developed based on two observers, respectively, such that the bipartite fixed-time output consensus of heterogeneous linear MASs can be achieved. Moreover, the upper bound of the settling time is independent of initial states of agents. Finally, the examples are given to demonstrate the results.

Regulation of Antiviral Immune Response by N 6-Methyladenosine of mRNA.

Host innate and adaptive immune responses play a vital role in clearing infected viruses. Meanwhile, viruses also evolve a series of mechanisms to weaken the host immune responses and evade immune defense. Recently, N 6-methyladenosine (m6A), the most prevalent mRNA modification, has been revealed to regulate multiple steps of RNA metabolism, such as mRNA splicing, localization, stabilization, and translation, thus participating in many biological phenomena, including viral infection. In the process of virus-host interaction, the m6A modification that presents on the virus RNA impedes capture by the pattern recognition receptors, and the m6A modification appearing on the host immune-related molecules regulate interferon response, immune cell differentiation, inflammatory cytokine production, and other immune responses induced by viral infection. This review summarizes the research advances about the regulatory role of m6A modification in the innate and adaptive immune responses during viral infections.

Hold Breath: Autonomic Neural Regulation of Innate Immunity to Defend Against SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel member of the genus of betacoronavirus, which caused a pandemic of coronavirus disease 2019 (COVID-19) worldwide. The innate immune system plays a critical role in eliminating the virus, which induces inflammatory cytokine and chemokine secretion, produces different interferons, and activates the adaptive immune system. Interactions between the autonomic nervous system and innate immunity release neurotransmitters or neuropeptides to balance the excess secretion of inflammatory cytokines, control the inflammation, and restore the host homeostasis. However, more neuro-immune mechanisms to defend against viral infection should be elucidated. Here, we mainly review and provide our understanding and viewpoint on the interaction between respiratory viral proteins and host cell receptors, innate immune responses to respiratory viral infection, and the autonomic neural regulation of the innate immune system to control respiratory viruses caused by lungs and airways inflammation.

Facial Emotion Recognition in Schizophrenia.

Deficits in facial emotion recognition are one of the most common cognitive impairments, and they have been extensively studied in various psychiatric disorders, especially in schizophrenia. However, there is still a lack of conclusive evidence about the factors associated with schizophrenia and impairment at each stage of the disease, which poses a challenge to the clinical management of patients. Based on this, we summarize facial emotion cognition among patients with schizophrenia, introduce the internationally recognized Bruce-Young face recognition model, and review the behavioral and event-related potential studies on the recognition of emotions at each stage of the face recognition process, including suggestions for the future direction of clinical research to explore the underlying mechanisms of schizophrenia.

[Effect of electroacupuncture on postpartum uterine contraction pain and uterine involution: a randomized controlled trial].

OBJECTIVE: To observe the effect of electroacupuncture on postpartum uterine contraction pain and uterine involution. METHODS: A total of 80 patients with postpartum uterine contraction pain were randomly divided into an observation group and a control group, 40 cases in each group. The observation group was treated with electroacupuncture at Dahe (KI 12), Zhongzhu (KI 15), Hegu (LI 4), Xuehai (SP 10), etc. for 30 min, once a day, 3 days were as one course, and 2 courses with 1-day interval were required. The control group was treated with oral Xinshenghua tablet, 4 tablets each time, 3 times a day for 7 days. Before treatment, 24, 48, 72 h into treatment and after treatment, the visual analogue scale (VAS) score was observed; the maximum anteroposterior diameter of uterine hemorrhage, the area of hemorrhage, the space between uterus fundus and umbilical cord, and the summation of three diameters of uterus before and after treatment were compared, and the time of postpartum uterine contraction pain disappeared was recorded in the two groups. RESULTS: Compared before treatment, the VAS scores of 24, 48, 72 h into treatment and after treatment were decreased in both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Compared before treatment, the maximum anteroposterior diameter of uterine hemorrhage, the area of hemorrhage and the summation of three diameters of uterus after treatment were decreased (P<0.05), the space between uterus fundus and umbilical cord was increased in both groups (P<0.05), and those in the observation group were superior to the control group (P<0.05). The number of days required to treat the uterine contraction pain in the observation group was shorter than the control group (P<0.05). CONCLUSION: Electroacupuncture can effectively relieve postpartum uterine contraction pain, accelerate the discharge of residual uterine hemorrhage in the uterine cavity, and promote uterine involution.

Bipartite output consensus of heterogeneous linear multi-agent systems by dynamic triggering observer.

In this paper, the bipartite output consensus problem of heterogeneous linear multi-agent systems (HL-MASs) is investigated. Compared with related works, both the cooperative interactions and antagonistic interactions between agents exist. First, a novel distributed dynamic triggering observer is designed to recover the leader's state. In order to avoid verifying the dynamic triggering condition continuously, a monitoring scheme is proposed. Then, the communication cost can be reduced. Next, we solve the bipartite output consensus problem of HL-MASs by both state feedback and output feedback control laws. Moreover, detailed analysis on the dynamic event triggering condition is conducted. It is shown that the lower bound of inter-execution time is larger than zero, so Zeno behaviour is excluded. The choice of parameters involved in the dynamic event triggering condition is also analysed. Finally, examples are given for demonstration.

[Clinical observation on the therapeutic effect of warm acupuncture on endometrial cavity fluid from in vitro fertilization-embryo transfer].

OBJECTIVE: To observe the clinical effect of warm acupuncture on endometrial cavity fluid (ECF) from in vitro fertilization-embryo transfer (IVF-ET), and to explore the mechanism of warm acupuncture on ECF. METHODS: Twenty-nine patients who were prepared for IVF-ET from 2016 to 2019 and whose transplantation was cancelled due to ECF found by vaginal B-ultrasound examination were divided into an observation group (14 cases) and a control group (15 cases) according to random number table method. The warm acupuncture was applied at Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3), Guilai (ST 29), Zigong (EX-CA 1), Zusanli (ST 36), Sanyinjiao (SP 6) after the end of menstruation in the observation group, the treatment lasted for 60 min, once a day, 5 times as a course, with 2 days interval between the courses and 3 consecutive courses of treatment were given, until the embryo transfer was performed in the IVF assisted pregnancy cycle. After the end of menstruation, fresh leonurus japonicus capsule was given in the control group, 3 times a day, 0.8 g each time, 7 days as a course, and 3 courses of continuous treatment were received, until the embryo transfer was performed in the IVF assisted pregnancy cycle. The changes of ECF before and after treatment, the time required to prepare for embryo transfer during IVF assisted pregnancy cycle, and the clinical outcome of embryo transfer were observed in the two groups. RESULTS: The decrease of ECF in the observation group was more significant than that in the control group (P<0.05). The time required for the embryo transfer in the IVF assisted pregnancy cycle in the observation group was shorter than that in the control group (P<0.05). The clinical pregnancy rate in the observation group was 42.9% (6/14), which was significantly higher than 26.7% (4/15) in the control group (P<0.05). CONCLUSION: Warm acupuncture may improve the clinical pregnancy rate by raising the local temperature of the lower abdomen, accelerating the blood circulation around the uterus and appendages, promoting the absorption of ECF, improving the uterine environment and endometrial receptivity.

HBV antigen and DNA loss from mouse serum is associated with novel vaccine-induced HBV surface antigen-specific cell-mediated immunity and cytokine production.

Therapeutic vaccination is a promising strategy for controlling chronic hepatitis B virus (HBV). Here, we tested whether several novel vaccination strategies could be used to induce HBV-specific adaptive immune responses and control/eradicate HBV in a mouse model. Robust HBV antigen-specific antibody responses were elicited by several vaccination strategies using a novel particle vaccine (HBSS1), which expresses a fusion of the S (amino acids [aa] 1-223) and preS1 (aa 21-47) antigens, and/or a recombinant adenovirus rAdSS1 vaccine. However, antigen-specific cell-mediated immunity and high levels of production of multiple cytokines were elicited only by heterologous prime-boost immunization; i.e., priming with the HBSS1 vaccine followed by a rAdSS1 boost. Furthermore, the most rapid loss of serum HBsAg, HBeAg and DNA was achieved by the novel vaccination regimen (priming with HBSS1 formulated with adjuvants [alum plus PolyI:C]), which was strongly associated with more potent and functional HBsAg-specific CD4+ and CD8+ T-cell responses and increased production of interleukin (IL)-2, interferon (IFN)-γ, tumor necrosis factor-α, IL-12, and IFN-γ-induced protein (IP)-10. Thus, our novel heterogeneous prime-boost vaccine regimen shows promise as a therapeutic strategy against HBV.

An alternative strategy to western blot as a confirmatory diagnostic test for HIV infection.

BACKGROUND: In China, western blot (WB) is the recommended procedure for the diagnosis of HIV infection. However, this technique is time consuming and labor intensive, and its complexity restricts wide application in resource-limited regions. OBJECTIVE: The aim of this study was to evaluate the efficacy of a dry blood spots (DBS)-urine paired enzyme-linked immunosorbent assay (ELISA) test, instead of WB, for HIV antibody detection. STUDY DESIGN: Plasma, DBS, and urine samples were collected from 1213 subjects from different populations. Two diagnostic testing strategies were conducted in parallel. The equivalence of the paired ELISA and WB strategies was assessed. RESULTS: A diagnosis of HIV was determined in 250 subjects according to the paired ELISA test, and in 249 according to the WB strategy. The discordant case was judged HIV-positive during follow-up. In total, 18 subjects were diagnosed with possible HIV using the paired ELISA test, among whom, 11 subjects tested negative with WB, and one was confirmed to be HIV-positive during follow-up. For the remaining 945 subjects, both strategies indicated a negative result. The kappa test indicated good conformity (kappa=0.954) between the two diagnostic strategies. CONCLUSION: The DBS-urine paired ELISA could be applied as an alternative to WB in HIV diagnosis, which would be valuable in resource-limited regions owing to the associated affordability and ease of use.

Development of a New Limiting-Antigen Avidity Dot Immuno-Gold Filtration Assay for HIV-1 Incidence.

Several laboratory assays on cross-sectional specimens for detecting recent HIV infections were developed, but these assays could not be applied in resource-limited and high HIV-incidence areas. This study describes the development of a rapid assay that can simultaneously detect the presence of HIV-1 antibodies of current and/or recent infection. The dot immuno-gold filtration assay (DIGFA) was used to detect recent infection on the principle of antibody avidity changes between recent and long-term infections. The dot immuno-gold silver staining filtration assay (DIGSSA) increases the sensitivity and accuracy of antibody detection by adding a silver staining step to the DIGFA. In the meantime the digital results were produced by the scanner for ambiguous specimens. Further, HIV-1 routine diagnostic antibody was detected simultaneously for improving practicability. The performance of the assays was then assessed through five serum panels with known serological statuses and seroconversion dates. The proportion of false recent infection (PFR) of the DIGSSA was obtained. Through the optimization of basic parameters for DIGSSA, six specimens were all classified correctly. DIGSSA demonstrated good repeatability and high sensitivity. The agreement of DIGSSA with the BED assay was 92.10% (κ = 0.65) and 95.36% with the LAg-Avidity assay (κ = 0.75). Moreover, the gray values of DIGSSA correlated well with BED ODn (R2 = 0.9397) and LAg-Avidity ODn (R2 = 0.9549). The PFR of DIGSSA was 2.73%, which was lower than that of the BED assay but higher than that of the LAg-Avidity assay. The DIGSSA can feasibly be applied to detect HIV infection and estimate HIV incidence.