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Objectives Escherichia coli producing metallo-β-lactamases with penicillin-binding protein 3 (PBP3) insertions have reduced susceptibility to aztreonam–avibactam and cefiderocol. Here, we analysed high-quality E. coli genomes for PBP3 insertions. Methods E. coli genomes (n  = 167 518) were retrieved from EnteroBase with CheckM2 for quality control, fastANI for species confirmation, multi-locus sequencing typing for sequence type (ST) determination and AMRFinderPlus for resistance gene identification. For PBP3 insertion analysis, we used Prokka for predicting coding sequences, BLAST+ for comparing resulted protein sequences and SnpEff for annotating variants. Results Among the included 159 341 genomes, PBP3 insertions with 11 variants were found in 2.01% (n  = 3198). The predominant variant is a duplication of 334–337 amino acids (aa) (94.75%, n  = 3030), comprising YRIN (65.92%, n  = 2108) and its single-aa-variant YRIK (28.83%, n  = 922), followed by a similar PYRI duplication of 333–336 (4.16%, n  = 133). The less common ones are a TIPY duplication of 331–334 (n  = 24) and its single-aa-variant TVPY's duplication: TVVPY (n  = 1), TVPYTVPY (n  = 1) and TVPYPVPY (n  = 1). Rare duplications include VGDR of 106–109 (n  = 3), ANALNIPL of 114–121 (n  = 3), AL of 567–568 (n  = 1) and TG of 584–585 (n  = 1). Insertion variants were detected across 62 countries on six continents, primarily in human samples, and associated with 85 STs, concentrated in high-risk clones ST410 (29.18%, n  = 1923), ST167 (23.40%, n  = 1740) and ST405 (10.56%, n  = 1334), with 83.32% (n  = 2218) encoding metallo-β-lactamase NDM. Conclusions Global spread of E. coli harbouring PBP3 insertion, often with NDM β-lactamase, high-risk ST410, ST167 and ST405 clones and various hosts, underscores the escalating antimicrobial resistance crisis and the urgency for a 'One Health' strategy. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) causes the most common type of severe lower respiratory tract infection worldwide, and the fusion (F) protein is a target for neutralizing antibodies and vaccine development. This study aimed to investigate the immunogenicity and efficacy of an mRNA-based RSV vaccine with an F protein sequence. Methods: We designed an mRNA construct encoding a modified RSV F protein, which was further developed into an LNP-encapsulated mRNA vaccine (LVRNA007). LVRNA007 was administered to mice and cotton rats, followed by immunogenicity analysis and viral challenge studies. Protection of rodents from the viral infection was evaluated based on the presence of the virus in the lung and pathological examination of respiratory tissues. Results: LVRNA007 induced robust humoral and cellular immune responses in both mice and cotton rats, with neutralization antibody levels in the immunized animals maintained at high levels for over one year. Vaccination of LVRNA007 also protected the rodents from RSV challenge, judged by the much decreased virus titer and the pathological score in the lung tissue. In addition, no vaccine-enhanced disease (VED) phenomenon was observed with LVRNA007 vaccination. Conclusions: Based on the preclinical immunogenicity and efficacy data, LVRNA007 could be a potential promising vaccine for prophylaxis of RSV infection. [ABSTRACT FROM AUTHOR]

Aiming at the problem of tracking failure caused by rotation, occlusion and deformation of moving target in video sequence, a tracking method based on multi-region segmentation of target was proposed. The target is divided into multiple overlapping regions, and then multiple regions that are relatively stable in the tracking process are selected for positioning, and then different target region weights are used to update different template updating strategies for the tracked target. In this way, the anti-blocking and anti-rotation ability of the algorithm can be increased. Experimental results show that the proposed method is adaptive to occlusion and rotation.

Imipenemase (IMP) is a metallo-β-lactamase that confers resistance to almost all β-lactams. Identification of IMP genes is essential for understanding and combatting antibiotic resistance. In this study, we report a pandrug-resistant Providencia strain from a human rectal swab. This strain carried 2 blaIMP carbapenemase genes, blaIMP-69 and blaIMP-4. IMP-69 is a novel IMP variant with an amino acid substitution at A21T compared with IMP-8. blaIMP-69 was found in a blaIMP-69-aacA4 array of an integron on a 165-kilobase (kb) IncC self-transmissible plasmid, whereas blaIMP-4 was located in a blaIMP-4-qacG-aacA4-catB3 array of an integron on a 19-kb nonself-transmissible plasmid. Such coexistence has the potential to allow the generation of new, hybrid blaIMP variants by homologous recombination. The blaIMP-69-carrying IncC plasmid belonged to the core-genome plasmid multilocus sequence typing (cgPMLST) 3.5 type. We found that cgPMLST 3.5 IncC plasmids have been circulating worldwide for decades and may represent a common vehicle mediating the spread of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Press-pack insulated gate bipolar transistor (IGBT) device is the key component in the voltage source converter high voltage direct current (VSC-HVDC) due the advantage of the short-circuit failure. However, it is difficult to analyse the IGBT short-circuit failure mode due to the complex packaging and the short failure time. This study presents a method on simulation for the short-circuit failure mode of the press-pack IGBT device. First, based on the structure of a single-chip 3.3 kV/50 A press-pack IGBT, a multi-physical field model was presented by considering the electro–mechanical–thermal coupling effects, so that the internal weak layer was found by comparing with the different sustained pressures. Then, an equivalent method is proposed by using the different aluminium–silicon reaction osmotic hole in the chip, and the models were presented to simulate the short-circuit failure. Furthermore, after short-circuit failure of the device, the thermal resistance variation of each later in press-pack IGBT device was obtained. Finally, the experiment on the steady state and the short-circuit tests were performed, by analysing the weak layer and the short-circuit failure position of the IGBT device, the proposed models and analysis were testified. The achievement is helpful to optimal design of the press-pack IGBT device to improve the VSC-HVDC converter reliability. [ABSTRACT FROM AUTHOR]

SDF-1 and CXCR4 are a chemokine and chemokine receptor pair playing critical roles in tumorigenesis. Overexpression of CXCR4 is a hallmark of many hematological malignancies including acute myeloid leukemia, chronic lymphocytic leukemia and non-Hodgkin’s lymphoma, and generally correlates with a poor prognosis. In this study, we developed a humanized anti-CXCR4 monoclonal antibody, LY2624587 as a potent CXCR4 antagonist that was advanced into clinical study for cancer. LY2624587 blocked SDF-1 binding to CXCR4 with an IC50 of 0.26 nM, and inhibited SDF-1-induced GTP binding with a Kb of 0.66 nM. In human lymphoma U937 and leukemia CCRF-CEM cells expressing endogenous CXCR4, LY2624587 inhibited SDF-1-induced cell migration with IC50 values of 3.7 and 0.26 nM, respectively. This antibody also inhibited CXCR4 and SDF-1 mediated cell signaling including activation of MAPK and AKT in tumor cells expressing CXCR4. Bifocal microscopic and flow cytometry analyses revealed that LY2624587 mediated receptor internalization and caused CXCR4 down-regulation on the cell surface. In human hematologic cancer cells, LY2624587 caused dose dependent apoptosis in vitro and in vivo. In mouse xenograft models developed with human leukemia and lymphoma cells expressing high levels of CXCR4, LY2624587 exhibited dose-dependent tumor growth inhibition and provided significant survival benefit in a disseminated lymphoma model. Collectively, we have demonstrated that CXCR4 inhibition by LY2624587 has the potential for the treatment of human hematological malignancies. [ABSTRACT FROM AUTHOR]

ABSTRACT We used accelerator mass spectrometry (AMS) 14C-dated sediments of the Holocene basal supratidal flat to upper tidal flat facies in 11 cores on the southern Yangtze delta plain to reconstruct relative sea levels of 8.5-8.0 cal ka BP. Three cores were further AMS 14C dated and used to examine the evolution of sedimentary geomorphological environments in response to the rapid sea-level rise during the early to mid-Holocene. Results demonstrate relative sea-level rise of around 30 mm a−1 from 8.5 to 8.3 cal ka BP and around 10 mm a−1 from 8.3 to 8.0 cal ka BP. Retrogradation from supratidal to lower tidal flat environments occurred in response to the rapid sea-level rise at 8.5-8.3 cal ka BP, and aggradation from middle to upper tidal flat occurred at 8.3-7.9 cal ka BP. Further retreat of the tidal flat at 7.9-7.2 cal ka BP implies a mean sea-level rise rate exceeding 5 mm a−1 at this time. We suggest that the rapid relative sea-level rise during 8.3-8.5 cal ka BP and subsequent slower rise caused drastic changes in the coastal zone and that these changes are key phenomena for understanding the coastal response to future sea-level rise. [ABSTRACT FROM AUTHOR]

The fatigue assessment of support structures is one of the most significant challenges in the design of offshore wind turbines (OWT). Fatigue analysis can be conducted in either the time-domain or the frequency-domain. The advantage of frequency-domain analysis is its time efficiency. This paper shows how the frequency domain method can be used to dimension lattice-type OWT towers such that they meet the fatigue criteria in the preliminary design stage. Two types of lattice towers, a three-legged and four-legged version, were redesigned in the fatigue limit state for the NREL 5 MW baseline wind turbine sited at a water depth of 35 m. The wall thickness of the members was chosen as the only variable and varied during the design process until the towers could survive for at least 20 years. In comparison with designs based upon ultimate strength, the mass of both types of towers increased no more than 30% when the fatigue limit state was considered. It is concluded that the lattice type structure requires only half as much material as its tubular counterpart. The three-legged tower is promising because of its simple geometry, even though it displayed a lower torsional stiffness than the four-legged tower. All the analyses in this paper were performed by an in-house FE code, intended for the early design stage of lattice towers. Once the optimum configuration is found in the early design stage, integrated time-domain analyses for the entire OWT system might be required to refine the design, taking all the nonlinear parameters into account. [ABSTRACT FROM AUTHOR]

Objectives: We performed an environmental sampling study to investigate the environmental contamination of SARS-CoV-2 by COVID-19 patients with prolonged PCR positive status of clinical samples. Methods: We sampled the air from rooms for nine COVID-19 patients with illness or positive PCR > 30 days, before and after nasopharyngeal/oropharyngeal swabbing and before and after nebulization treatment. We also sampled patients' surroundings and healthcare workers' personal protection equipment (PPE) in a non-ICU ward. SARS-CoV-2 was detected by PCR. Results: Eighty-eight samples were collected from high-touch surfaces and floors in patient rooms and toilets, with only the bedsheets of two patients and one toilet positive for SARS-CoV-2. All air samples (n = 34) were negative for SARS-CoV-2. Fifty-five samples collected from PPE were all negative. Conclusion: Contamination of near-patient surroundings was uncommon for COVID-19 patients with prolonged PCR positive status if environmental cleaning/disinfection were performed rigorously. Airborne transmission of SARS-CoV-2 was unlikely in these non-ICU settings. [ABSTRACT FROM AUTHOR]

We found an unusual Escherichia coli strain with resistance to colistin, carbapenem and amikacin from sewage. We therefore characterized the strain and determined the co-transfer of the resistance determinants. Whole genome sequencing was performed using both Illumina HiSeq X10 and MinION sequencers. Short and long reads were subjected to de novo hybrid assembly. Sequence type, antimicrobial resistance genes and plasmid replicons were identified from the genome sequences. Phylogenetic analysis of all IncHI2 plasmids carrying mcr-1 available in GenBank was performed based on core genes. Conjugation experiments were performed. mcr-3.5 was cloned into E. coli DH5α. The strain belonged to ST410, a type with a global distribution. Two colistin-resistant genes, mcr-1.1 and mcr-3.5, a carbapenemase gene blaNDM-5, and a 16S methylase gene rmtB were identified on different plasmids of IncHI2(ST3)/IncN, IncP, IncX3 and IncFII, respectively. All of the four plasmids were self-transmissible and mcr-1.1, mcr-3.5, blaNDM-5 and rmtB were transferred together. mcr-1-carrying IncHI2 plasmids belonged to several sequence types with ST3 and ST4 being predominant. MIC of colistin (4 μg/ml) for DH5α containing mcr-3.5 was identical to that containing the original mcr-3 variant. In conclusion, carbapenem resistance, colistin resistance and high-level aminoglycoside resistance can be transferred together even when their encoding genes are not located on the same plasmid. The co-transfer of multiple clinically-important antimicrobial resistance represents a particular challenge for clinical treatment and infection control in healthcare settings. Isolates with resistance to both carbapenem and colistin are not restricted to a given sequence type but rather are diverse in clonal background, which warrants further surveillance. The amino acid substitutions of MCR-3.5 have not altered its activity against colistin. [ABSTRACT FROM AUTHOR]

Heart failure often develops after acute myocardial infarction because the injured myocardial tissue fails to recover or regenerate. Stem cell transplantation using adult cell sources, such as adipose-derived stromal vascular fraction (SVF), draws extensive attention. In this study, SVF cells were isolated from rat adipose tissue and cultivated on enzyme-crosslinked gelatin hydrogels. Morphological features of cell development and spontaneous beating behavior from these cells were observed and recorded. Cardiac phenotypes were characterized via immunofluorescence staining, and the expression of cardiac-specific genes was measured via RT-PCR. The functional assessment of SVF-derived cardiomyocyte-like cells (SVF-CMs) was performed by detecting cellular calcium transient activities and pharmacological responses. Results showed that most SVF-CMs exhibited elongated myotubule shapes and expressed cardiac troponin I strongly. SVF-CMs expressed cardiac-specific RNA (including transcription factors GATA binding protein 4) and myocyte enhancer factor 2c, as well as the structural proteins, namely, sarcomere actinin alpha 2, cardiac troponin I type 3, cardiac troponin T type 2, and cardiac gap junction protein alpha 1. Their beating mode, calcium activities, and pharmacological responses were similar to those of native CMs. Spontaneously beating SVF-CMs can be derived from adipose tissue-derived SVFs, and enzyme-crosslinked gelatin hydrogel promoted the cardiac differentiation of SVF cells. [ABSTRACT FROM AUTHOR]

The South China Sea (SCS) is sensitive to the East Asian monsoon (EAM) and changes in the Western Pacific. However, because of the difficulty of sampling and lack of data in the central SCS, many uncertainties remain the primary driving force of paleoclimatic variations. Here, a sediment core JL136, from the central SCS, was used to evaluate variations of sea surface temperature (SST) and salinity (SSS) during the Holocene, and then the corresponding influencing factors were analyzed, based on measured Mg/Ca ratio and stable isotopic compositions (δ18O and δ13C) of planktonic foraminifera Globigerinoides ruber sensu stricto (s.s.). The results show that the Mg/Ca-SST change is consistent with the speleothem δ18O records across most Asian monsoon regions on the Holocene long-term trend, revealing that the central SCS record is a response to the East Asian Summer Monsoon (EASM) intensity changes induced by Northern Hemisphere summer insolation (NHSI) variation. During the early Holocene (11.6–8.8 ka), SSS was low with an average of 32.7 psu, which may be related to palaeogeographic variations with sea level changes and the increased coastal water due to the opening of the Taiwan Strait. During the mid-late Holocene, high salinity ocean water was fully exchanged with the SCS due to the influence of high sea level, with an overall higher salinity in the SCS compared with the early Holocene (average 33.8 psu). In addition, the SSS broadly showed an increasing trend, which may be mainly controlled by the weakening EASM intensity and the decreasing precipitation during the low NHSI. • SST and SSS changes in the abyssal area of SCS during the Holocene are reconstructed. • SST in the abyssal area responses to the changes of the East Asian Summer Monsoon intensity stems from the Northern Hemisphere summer insolation. • SSS may be related to the palaeogeographic variations with sea level changes and the change of monsoon precipitation caused by the EASM intensity. [ABSTRACT FROM AUTHOR]