Intrauterine ultrasound phenotyping, molecular characteristics, and postnatal follow-up of fetuses with the 15q11.2 BP1-BP2 microdeletion syndrome: a single-center, retrospective clinical study.

OBJECTIVES: The 15q11.2 BP1-BP2 microdeletion is associated with neurodevelopmental diseases. However, most studies on this microdeletion have focused on adults and children. Thus, in this study, we summarized the molecular characteristics of fetuses with the 15q11.2 BP1-BP2 microdeletion and their postnatal follow-up to guide prenatal diagnosis. METHODS: Ten thousand fetuses were retrospectively subjected to karyotype analysis and chromosome microarray analysis. RESULTS: Chromosome microarray analysis revealed that 37 (0.4%) of the 10,000 fetuses had 15q11.2 BP1-BP2 microdeletions. The fragment size of the 15q11.2 BP1-BP2 region was approximately 312-855 kb and encompassed TUBGCP5, CYFIP1, NIPA2, and NIPA1 genes. Twenty-five of the 37 fetuses with this microdeletion showed phenotypic abnormalities. The most common ultrasonic structural abnormality was congenital heart disease, followed by renal dysplasia and Dandy-Walker malformation. The 15q11.2 BP1-BP2 microdeletion was inherited from the father and mother in 6 and 10 cases, respectively, and de novo inherited in 4 cases. In the postnatal follow-up, 16.1% of the children had postnatal abnormalities. CONCLUSION: Fetuses with the 15q11.2 BP1-BP2 microdeletion showed high proportions of phenotypic abnormalities, but the specificity of penetrance was low. Thus, fetuses with this syndrome are potentially at a higher risk of postnatal growth/behavioral problems and require continuous monitoring of growth and development.

Prenatal diagnosis of fetal digestive system malformations and pregnancy outcomes at a tertiary referral center in Fujian, China: A retrospective study.

Fetal digestive system malformations (DSMs) are correlated with chromosomal anomalies. The prenatal diagnosis of DSMs allows for timely treatment and reduces perinatal morbidity and mortality. However, genetic screening for fetal DSMs is rarely reported. This study aimed to investigate genetic etiology and pregnancy outcomes in cases of fetal DSM by analyzing correlations between DSM types and chromosomal anomalies. This retrospective single-center study included 126 fetuses in whom DSMs were detected via prenatal ultrasonography. Genetic etiology was investigated using conventional karyotyping, chromosome microarray analysis (CMA), and whole-exome sequencing (WES). DSMs were categorized as simple DSM (Group A), DSM combined with abnormal ultrasound soft markers (Group B), and DSM combined with comorbidities of other systems (Group C). Abnormal karyotypes were detected in 11/126 (8.7 %) fetuses. Four more pathogenic copy number variants (CNVs) were detected using CMA, increasing the detection rate to 11.9 %. The detection rates significantly differed between the three DSM types (1.78 %, 8.11 %, and 33.33 % in Groups A, B, and C, respectively). The overall adverse pregnancy outcome rate was 33.9 %, and 11.5 %, 23.5 %, and 81.3 %, (P < 0.001), respectively, in Groups A, B, and C. Out of 83 live births, three neonates died, 26 underwent postnatal surgery with 24 favorable outcomes, and 54 did not undergo surgery and were basically normal. Two neonates who underwent WES were diagnosed with CHD7-associated Charge syndrome and JAG1-associated Alagille syndrome, respectively. Our findings demonstrate that fetal DSM is closely related to chromosome aneuploidies, CNVs, and point mutations. The prognoses of most fetuses with simple DSM and those with comorbid abnormal ultrasound soft markers were favorable in the absence of chromosomal anomalies and severe structural malformations, provided they underwent timely surgery as neonates. These findings provide guidance for the prenatal diagnosis and clinical management of fetal DSMs and the genetic counseling of parents.

Precise solid-phase synthesis of CoFe@FeOx nanoparticles for efficient polysulfide regulation in lithium/sodium-sulfur batteries.

Complex metal nanoparticles distributed uniformly on supports demonstrate distinctive physicochemical properties and thus attract a wide attention for applications. The commonly used wet chemistry methods display limitations to achieve the nanoparticle structure design and uniform dispersion simultaneously. Solid-phase synthesis serves as an interesting strategy which can achieve the fabrication of complex metal nanoparticles on supports. Herein, the solid-phase synthesis strategy is developed to precisely synthesize uniformly distributed CoFe@FeOx core@shell nanoparticles. Fe atoms are preferentially exsolved from CoFe alloy bulk to the surface and then be carburized into a FexC shell under thermal syngas atmosphere, subsequently the formed FexC shell is passivated by air, obtaining CoFe@FeOx with a CoFe alloy core and a FeOx shell. This strategy is universal for the synthesis of MFe@FeOx (M = Co, Ni, Mn). The CoFe@FeOx exhibits bifunctional effect on regulating polysulfides as the separator coating layer for Li-S and Na-S batteries. This method could be developed into solid-phase synthetic systems to construct well distributed complex metal nanoparticles.

Reactant enrichment in hollow void of Pt NPs@MnOx nanoreactors for boosting hydrogenation performance.

In confined mesoscopic spaces, the unraveling of a catalytic mechanism with complex mass transfer and adsorption processes such as reactant enrichment is a great challenge. In this study, a hollow nanoarchitecture of MnOx-encapsulated Pt nanoparticles was designed as a nanoreactor to investigate the reactant enrichment in a mesoscopic hollow void. By employing advanced characterization techniques, we found that the reactant-enrichment behavior is derived from directional diffusion of the reactant driven through the local concentration gradient and this increased the amount of reactant. Combining experimental results with density functional theory calculations, the superior cinnamyl alcohol (COL) selectivity originates from the selective adsorption of cinnamaldehyde (CAL) and the rapid formation and desorption of COL in the MnOx shell. The superb performance of 95% CAL conversion and 95% COL selectivity is obtained at only 0.5 MPa H2 and 40 min. Our findings showcase that a rationally designed nanoreactor could boost catalytic performance in chemoselective hydrogenation, which can be of great aid and potential in various application scenarios.

Adsorption Mechanisms of Glyphosate on Ferrihydrite: Effects of Al Substitution and Aggregation State.

Ferrihydrite is one of the most reactive iron (Fe) (oxyhydr)oxides in soils, but the adsorption mechanisms of glyphosate, the most widely used herbicide, on ferrihydrite remain unknown. Here, we determined the adsorption mechanisms of glyphosate on pristine and Al-substituted ferrihydrites with aggregated and dispersed states using macroscopic adsorption experiments, zeta potential, phosphorus K-edge X-ray absorption near-edge structure spectroscopy, in situ attenuated total reflectance Fourier transform infrared spectroscopy coupled with two-dimensional correlation spectroscopy, and multivariate curve resolution analyses. Aggregation of ferrihydrite decreases the glyphosate adsorption capacity. The partial substitution of Al in ferrihydrite inhibits glyphosate adsorption on aggregated ferrihydrite due to the decrease of external specific surface area, while it promotes glyphosate adsorption on dispersed ferrihydrite, which is ascribed to the increase of surface positive charge. Glyphosate predominately forms protonated and deprotonated, depending on the sorption pH, monodentate-mononuclear complexes (MMH1/MMH0, 77-90%) on ferrihydrites, besides minor deprotonated bidentate-binuclear complexes (BBH0, 23-10%). Both Al incorporation and a low pH favor the formation of the BB complex. The adsorbed glyphosate preferentially forms the MM complex on ferrihydrite and preferentially bonds with the Al-OH sites on Al-substituted ferrihydrite. These new insights are expected to be useful in predicting the environmental fate of glyphosate in ferrihydrite-rich environments.

Prenatal diagnosis of 15q11.2 microdeletion fetuses in Eastern China: 21 case series and literature review.

OBJECTIVE: 15q11.2 microdeletion can lead to syndromes affecting the nervous system. However, 15q11.2 microdeletion has large phenotypic differences and incomplete penetrance, which brings challenges to prenatal diagnosis. We reported 21 cases of 15q11.2 microdeletion fetuses in Eastern China and reviewed literature on the prenatal clinical characteristics related to the deletion variants to provide a basis for prenatal genetic counseling. METHODS: The clinical data of 21 cases of 15q11.2 microdeletion fetuses collected from June 2018 to September 2021 were retrospectively analyzed, and chromosomal microarray analysis was performed. The reported prenatal clinical features of 15q11.2 microdeletion fetuses were reviewed and summarized. A meta-analysis of 20 studies was performed to test heterogeneity, data integration, and sensitivity on the correlation between 15q11.2 microdeletion and neuropsychiatric diseases. RESULTS: The median age of the women was 29.5 years. The median gestational age at interventional examination was 24 weeks. All fetuses showed deletion variants of the 15q11.2 fragment, and the median deletion range was approximately 0.48 MB. Ultrasound of five cases showed no abnormalities; however, four of them showed a high risk of Down's syndrome (risk values were 1/184, 1/128, 1/47, and 1/54, respectively). The remaining 16 fetuses showed congenital heart disease (7/16), elevated nuchal translucency (5/16), abnormal brain structure (2/16) and renal disease (2/16). In a literature review of 82 prenatal cases, 44% (36/82) had abnormal ultrasound features, 31% (11/36) showed abnormal nuchal translucency, approximately 28% (10/36) showed abnormal cardiac structure, and 14% (5/36) had brain structural abnormalities. The meta-analysis revealed that the frequency of the 15q11.2 microdeletion mutation in patients with schizophrenia and epilepsy was significantly higher (odds ratio 2.04, 95% confidence interval: 1.78-2.33, p < 0.00001; odds ratio 5.23, 95% confidence interval: 2.83-9.67, p < 0.00001) than that in normal individuals. CONCLUSION: More than half of the 15q11.2 microdeletion cases presented no abnormalities in prenatal ultrasound examination. The cases with ultrasound features mainly showed isolated malformations such as elevated nuchal translucency, congenital heart disease, and brain structural abnormalities. Postpartum 15q11.2 microdeletion patients are at an increased risk of suffering from schizophrenia, epilepsy, and other neurological and mental diseases from 15q11.2 microdeletion. Therefore, prenatal diagnosis of 15q11.2 microdeletion not only depends on molecular diagnostic techniques but also requires cautious genetic counseling.

Performance of Two Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS) Systems for Identification of the Viridans Group Streptococci.

Background: Due to similar colony morphology among viridans group streptococci (VGS), the differentiation of VGS species remains difficult in routine clinical microbiology. Recently, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) has been described as a fast method for identifying various bacteria at species level, and also for the VGS strains. Methods: A total of 277 VGS isolates were identified with the two MALDI-TOF MS systems (VITEK MS and Bruker Biotyper). The tuf and rpoB gene sequencing was used as the reference identification method for comparison. Results: Based on tuf and rpoB gene sequencing, 84 isolates were S. pneumoniae and 193 strains were other VGS isolates including S. anginosus group (n=91, 47.2%), S. mitis group (n=80, 41.5%), S. bovis group (n=11, 5.7%), S. salivarius group (n=10, 5.2%), and S. mutans group (n=1, 0.5%). VITEK MS and Bruker Biotyper accurately identified 94.6% and 89.9% of all VGS isolates, respectively. VITEK MS showed better identification results than Bruker Biotyper for S. mitis group including S. pneumoniae and S. bovis group, but for other VGS isolates, two MALDI-TOF MS systems showed comparable identification performance. However, VITEK MS was able to identify S. gallolyticus to the subspecies level with high-confidence (S. gallolyticus ssp. pasteurianus), while the Bruker Biotyper system could not. While Bruker Biotyper system could be able to correctly differentiate the subspecies of S. salivarius from S. vestibularis, VITEK MS poorly identify. Conclusion: This study demonstrated that two MALDI-TOF MS systems allowed discrimination for most VGS isolates with different identification performance, but Bruker Biotyper could produce more misidentifications and VITEK MS system. It is crucial to be familiar with the performance of MALDI-TOF MS systems used in clinical microbiology.

Intestinal transport mechanism of HA-LOR microspheres with different molecular weights in the MDCK cell model.

In this study, LOR microspheres with different molecular weights of hyaluronic acid (HA) were prepared by spray drying method using the second-generation antihistamine loratadine (LOR) as a model drug. A small intestinal transmembrane transport model was used to study the effect of HA molecular weight on small intestinal transmembrane transport and to explore the mechanism of HA molecular weight on intestinal absorption. The transmembrane transport of HA-LOR microspheres of different molecular weights was investigated by adding several inhibitors related to drug transmembrane transport and cellular function in the MDCK cell model. The results showed that low, medium and high molecular weight HA in HA-LOR microspheres had no effect on P-gp efflux and macrocytidine and had no effect on the transmembrane of LOR microspheres; medium molecular weight HA could affect Ca2+ channel and has an effect on the transmembrane transport of LOR microspheres; high molecular weight HA can affect clathrin-mediated endocytosis, lipid microcapsule-mediated endocytosis and endosomes, indicating that high molecular weight HA-LOR microspheres are effective in the intestinal tract. The uptake of LOR can be facilitated by the action of uptake enhancers, the action of Ca2+ channels and the uptake of ATP to LOR.

Molecular Epidemiology of Group B Streptococcus Isolates from Pregnant Women with Premature Rupture of Membranes in Fuzhou, China.

Objective: This study investigated the molecular epidemiology of Group B Streptococcus (GBS) in pregnant women with premature rupture of membranes (PROM) in Fuzhou region of China as a source of clinical reference. Methods: GBS isolates were obtained from pregnant women with PROM. All isolates were genotyped, serotyped, and tested for drug-resistance and virulence genes using PCR and DNA sequencing. Antibiotic susceptibility testing was performed using the Vitek® 2 automated system. Results: Among the 140 GBS isolates, seventeen sequence types (STs) were identified, of which ST19 (20.0%) was the most prevalent, followed by ST862, ST10, and ST12. Three clonal complexes (CC19, CC10 and CC1) were identified. The predominant serotype was III (45.7%), followed by V (23.6%), Ib (18.6%), Ia (7.1%), and II (3.6%). The prevalence of multidrug resistance was 72.8% (102/140). All isolates were susceptible to penicillin G, ampicillin, quinupristin, linezolid, vancomycin, and tigecycline. The majority of isolates were resistant to erythromycin (70.0%), clindamycin (72.1%), and tetracycline (81.4%), and 28.6% of isolates were resistant to levofloxacin and moxifloxacin. Of the 98 erythromycin-resistant strains, mreA, ermB, mefA, mefE, ermA, and ermTR were detected in 100%, 70.4%, 49.0%, 22.4%, 13.3%, and 9.2%, respectively. No linB was detected among 101 clindamycin-resistant strains. Of the 114 tetracycline-resistant strains, tetM, tetK, tetL and tetO were detected in 52.6%, 61.4%, 7.9%, and 23.7%, respectively. Regarding virulence genes, all strains carried rib and hylB, followed by scpB (98.6%), and bca (80.7%), whereas only one strain carried bac. Conclusion: ST19/III and ST862/III were the most prevalent GBS subtypes. Penicillin G remains a first-line antibiotic for intrapartum antibiotic prophylaxis and treatment of GBS infections. The prevalence of resistance to clindamycin, erythromycin, and tetracycline is high among GBS isolates in the Fuzhou region. ST862 and ST651 are emerging animal origin STs in human infections, and may become potential zoonotic threats.

Enhancing Catalytic Performance through Subsurface Chemistry: The Case of C2H2 Semihydrogenation over Pd Catalysts.

Subsurface chemistry in heterogeneous catalysis plays an important role in tuning catalytic performance. Aiming to unravel the role of subsurface heteroatoms, C2H2 semihydrogenation on a series of Pd catalysts doped with subsurface heteroatom H, B, C, N, P, or S was fully investigated by density functional theory (DFT) calculations together with microkinetic modeling. The obtained results showed that catalytic performance toward C2H2 semihydrogenation was affected significantly by the type and coverage of subsurface heteroatoms. The Pd-B0.5 and Pd-C0.5 catalysts with 1/2 monolayer (ML) heteroatom coverage, as well as Pd-N, Pd-P, and Pd-S catalysts with 1/16 ML heteroatom coverage, were screened to not only obviously improve C2H4 selectivity and activity but also effectively suppress green oil. The essential reason for subsurface heteroatoms in tuning catalytic performance is attributed to the distinctive surface Pd electronic and geometric structures caused by subsurface heteroatoms. In the Pd-B0.5 and Pd-C0.5 catalysts, the Pd surface electronic and geometric effects play the dominant role, while the geometric effect plays a key role in the Pd-N, Pd-P, and Pd-S catalysts. The findings provide theoretically valuable information for designing high-performance metal catalysts in alkyne semihydrogenation through subsurface chemistry.

Clinical findings and genetic analysis of patients with copy number variants involving 17p13.3 using a single nucleotide polymorphism array: a single-center experience.

BACKGROUND: 17p13.3 microdeletions or microduplications (collectively known as copy number variants or CNVs) have been described in individuals with neurodevelopmental disorders. However, 17p13.3 CNVs were rarely reported in fetuses. This study aims to investigate the clinical significance of 17p13.3 CNVs with varied sizes and gene content in prenatal and postnatal samples. METHODS: Eight cases with 17p13.3 CNVs out of 8806 samples that had been subjected to single nucleotide polymorphism array analysis were retrospectively analyzed, along with karyotyping, clinical features, and follow-up. RESULTS: Eight cases with 17p13.3 CNVs consisted of five fetuses, one aborted embryo and two probands manifested severe congenital defects. The indications of prenatal testing varied considerably for the five fetuses, including ultrasound abnormalities (n = 3), segmental deletions indicated by non-invasive prenatal testing (n = 1), and intellectual disability in the mother of one fetus (n = 1). Of them, two and six harbored copy number gains and losses involving 17p13.3, respectively. The size of the detected 17p13.3 CNVs ranged from 576 kb to 5.7 Mb. Case 1 was diagnosed with 17p13.3 duplication syndrome, and cases 4, 6, and 7 with Miller-Dieker syndrome (MDS). Microdeletions of the 17p13.3 region in two cases (cases 5 and 8) involving YWHAE and CRK, sparing PAFAH1B1, were classified as pathogenic. Case 2 harbored a 576 kb microduplication, encompassing YWHAE and CRK but not PAFAH1B1, which was of maternal origin and considered a variant of uncertain significance. Case 3 carried one 74.2 Mb mosaic duplication of approximately 3.5 on chromosome 17p13.2q25.3, and two deletions at 17p13.3p13.2 and 17q25.3. The karyotype of case 3 was 46,XY,r(17)(p13q25). For five fetuses, only case 2 continued gestation and showed normal development at the age of 15 months; the others were subjected to termination of pregnancy. CONCLUSION: The clinical findings of 17p13.3 microdeletions or microduplications varied among subjects, and 17p13.3 CNVs often differ in size and gene content. Microdeletions or microduplications containing the typical MDS region, as well as the microdeletions involving YWHAE and CRK, could be classified as pathogenic. The clinical significance of small duplications including YWHAE and CRK but not PAFAH1B1 remains uncertain, for which parental testing and clinical heterogeneity should be considered in genetic counseling.

Prenatal diagnosis of fetuses with region of homozygosity detected by single nucleotide polymorphism array: a retrospective cohort study.

Region of homozygosity (ROH) is classified as uniparental disomy (UPD) or identity by descent, depending on its origin. To explore the clinical relevance of ROH in prenatal diagnoses, we reviewed 5063 fetal samples subjected to single nucleotide polymorphism array at our center over 5 years. ROH cases meeting our reporting threshold were further analyzed. ROHs were detected in 22 fetuses (0.43%, 22/5063), of which, 77.3% (17/22) showed a ROH on a single chromosome and 22.7% (5/22) showed multiple ROHs on different chromosomes. Among 5063 fetuses undergoing invasive prenatal diagnoses owing to various indications, five cases were identified as UPDs with a rate of ~1/1000. We observed clinically relevant UPDs in two cases related to Prader-Willi syndrome and transient neonatal diabetes mellitus. Of note, one case showed 50% mosaicism for trisomy 2 in amniotic fluid, whereas a complete UPD (2) was observed in umbilical cord blood. Trio whole-exome sequencing was performed for three cases. Clinically relevant variants were identified in two cases, one of which, NM_000302:c.2071_2072insCC (p.R693Qfs*122) in PLOD1 located in the ROH, may be related to Ehlers-Danlos syndrome, kyphoscoliotic type, 1. Overall, 72.7% (16/22) of the ROH carriers showed ultrasound abnormalities, of whom eight (50%, 8/16) had adverse perinatal outcomes. Our study demonstrates that the clinical relevance of ROHs should be examined regarding fetuses with ROHs occurring on imprinted chromosomes or those derived from consanguineous parents in prenatal diagnoses; imprinting disorders and/or autosomal recessive diseases attributed to ROHs should be considered during genetic counseling.

The impacts of aging pH and time of acid mine drainage solutions on Fe mineralogy and chemical fractions of heavy metals in the sediments.

Fe (oxyhydr)oxides are the main components that accumulate heavy metals (HMs) in the acid mine drainage (AMD) sediments, but how the aging pH and time of AMD solution affects the Fe mineralogy and HMs speciation remains ambiguous. Herein, we determined the impacts of aging pH and time on the Fe mineralogy and chemical fractions of HMs in the sediments from Dabaoshan mining area using mineral characterizations, chemical extraction, and AMD solution incubation. For the natural AMD sediments, jarosite and goethite are the major Fe (oxyhydr)oxides in sample S1 with solution pH 2.68, while schwertmannite is dominant in sample S2 with solution pH 6.78, co-existing minor ferrihydrite. With increasing the AMD solution pH, the total contents of HMs (expect for As) and the reducible fraction of HMs (expect for Pb) in the sediments both increase. The HMs of Mn, Zn, Ni, and Cd are mainly associated with Fe (oxyhydr)oxides, while Pb possibly exists as Pb-bearing minerals (e.g., PbSO4) in the sediments. The oxidizable fraction of all HMs is negligible in both sediments. When the AMD solution of S1 was aged at different pHs, schwertmannite is dominant initially at all pHs, with a higher crystallinity being at a lower pH. With increasing aging time, the pre-formed schwertmannite transforms to goethite and jarosite at pH ≤ 3, while it keeps stable at pH 5 and 7 due to the accumulation of more HMs. These new insights are essential to assess the mobility and availability of HMs in the AMD-affected areas.

Syngas Conversion to C2 Species over WC and M/WC (M = Cu or Rh) Catalysts: Identifying the Function of Surface Termination and Supported Metal Type.

Improving the selectivity and activity of C2 species from syngas is still a challenge. In this work, catalysts with monolayer Cu or Rh supported over WC with different surface terminations (M/WC (M = Cu or Rh)) are rationally designed to facilitate C2 species generation. The complete reaction network is analyzed by DFT calculations. Microkinetics modeling is utilized to consider the experimental reaction temperature, pressure, and the coverage of the species. The thermal stabilities of the M/WC (M = Cu or Rh) catalysts are confirmed by AIMD simulations. The results show that the surface termination and supported metal types in the M/WC (M = Cu or Rh) catalysts can alter the existence form of abundant CHx (x = 1-3) monomer, as well as the activity and selectivity of CHx monomer and C2 species. Among these, only the Cu/WC-C catalyst is screened out to achieve outstanding activity and selectivity for C2H2 generation, attributing to that the synergistic effect of the subsurface C atoms and the surface monolayer Cu atoms presents the noble-metal-like character to promote the generation of CHx and C2 species. This work demonstrates a new possibility for rational construction of other catalysts with the non-noble metal supported by the metal carbide, adjusting the surface termination of metal carbide and the supported metal types can present the noble-metal-like character to tune catalytic performance of C2 species from syngas.

Genetic Characteristics and Microbiological Profile of Hypermucoviscous Multidrug-Resistant Klebsiella variicola Coproducing IMP-4 and NDM-1 Carbapenemases.

We report here a hypermucoviscous, New Delhi metallo-ß-lactamase 1 (NDM-1) and imipenemase 4 (IMP-4) carbapenemases-coproducing Klebsiella variicola isolate obtained from a pediatric patient. This strain was resistant to carbapenems and most other ß-lactams. Although hypermucoviscous, this strain possessed attenuated virulence according to serum killing assay and Galleria mellonella infection model. Notably, two copies of blaNDM-1 were contained on two tandem ISCR1 elements and coexisted with blaIMP-4 in a novel hybrid multidrug resistance plasmid. This is the first description of the coexistence of blaNDM-1 and blaIMP-4 in a single plasmid of hypermucoviscous K. variicola. IMPORTANCE As an important member of the Klebsiella pneumoniae complex, Klebsiella variicola is poorly studied as an emerging human pathogen. We, for the first time, report a unique K. variicola isolated from a pediatric patient in China. This isolate exhibited hypermucoviscosity, a classic hypervirulence characteristic of K. pneumoniae, and contained multiple carbapenem-resistant genes, including blaIMP-1 and blaNDM-1. Interestingly, these antimicrobial resistance genes were located on a novel hybrid plasmid, and our results suggested that this plasmid might have been introduced from K. pneumoniae and undergone a series of integration and recombination evolutionary events. Overall, our study provides more insight into K. variicola and highlights its superior capability to acquire and maintain foreign resistance genes.

Chk1 suppression leads to a reduction in the enhanced radiation-induced invasive capability on breast cancer cells.

Radiation therapy is generally effective for treating breast cancers. However, approximately 30% of patients with breast cancer experience occasional post-treatment local and distant metastasis. Low-dose (0.5 Gy) irradiation is a risk factor that promotes the invasiveness of breast cancers. Although an inhibitor of checkpoint kinase 1 (Chk1) suppresses the growth and motility of breast cancer cell lines, no study has investigated the effects of the combined use of a Chk1 inhibitor and radiation on cancer metastasis. Here, we addressed this question by treating the human breast cancer cell line MDA-MB-231 (in vitro) and mouse mammary tumor cell line 4 T1 (in vitro and in vivo) with γ-irradiation and the Chk1 inhibitor PD407824. Low-dose γ-irradiation promoted invasiveness, which was suppressed by PD407824. Comprehensive gene expression analysis revealed that low-dose γ-irradiation upregulated the mRNA and protein levels of S100A4, the both of which were downregulated by PD407824. We conclude that PD407824 suppresses the expression of S100A4. As the result, γ-irradiation-induced cell invasiveness were inhibited.

Molecular-Scale Understanding of Sulfate Exchange from Schwertmannite by Chromate Versus Arsenate.

Schwertmannite effectively sorbs chromate (Cr(VI)), yet the sorption mechanisms remain elusive. We determined the Cr(VI) sorption mechanisms on schwertmannite at pH 3.2 and 5 using combined macroscopic sorption experiments with molecular-scale characterization and by comparing them to arsenate (As(V)) sorption. Cr(VI) adsorbs as bidentate-binuclear (BB) inner-sphere complexes through exchanging more sulfate and less >Fe-OH/OH2, with 0.59-0.71 sulfate released per Cr(VI) sorbed. While As(V) also forms BB complexes, it exchanges sulfate and >Fe-OH/OH2 equally with 0.49-0.52 sulfate released per As(V) sorbed. At high As(V) loadings, As(V) precipitates as amorphous FeAsO4, particularly at low pH. The abovementioned differences between Cr(VI) and As(V) can be related to their different ionic radii and binding strength. Moreover, Cr(VI) and As(V) preferentially exchange sulfate inner-sphere complexes, increasing the proportion of sulfate outer-sphere complexes in schwertmannite. In turn, the concentration of sulfate outer-sphere complexes increases and then decreases with increasing Cr(VI) loading. Results suggest that an oxyanion, which would form inner-sphere complexes on a mineral surface, preferentially exchanges inner-spherically bound oxyanions than outer-spherically bound ones on the surface, even though both are exchanged. This study improves our understanding of the sorption of oxyanions on schwertmannite and their capabilities to template schwertmannite formation and stabilize its structure.

Molecular epidemiology of Carbapenem-resistant Klebsiella pneumoniae in a paediatric hospital in China.

OBJECTIVE: We investigated the epidemiological characteristics of drug resistance and virulence factors of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from paediatric patients in Shanghai. METHODS: CRKP strains were consecutively collected between January and December in 2018. Antimicrobial susceptibility was determined by VITEK 2 compact. Polymerase chain reaction (PCR) was used to analyse drug resistance determinants, virulence genes and plasmid types. wzi sequencing and multilocus sequence typing was used to determine clonal relatedness. RESULTS: Among 172 CRKP strains, blaKPC-2 and blaNDM-5 were the predominant carbapenemase genes. Compared with NDM-5, KPC-2 producers showed higher resistance rates to fluoroquinolones and aminoglycosides. The majority of KPC-2 producers belonged to KL64-ST11 background, while NDM-5 producers were mainly identified as KL62-ST48. Plasmid typing shown that IncF and IncFIB were the most prevalent plasmids in KPC-2 producers and IncX3 was widely spread in NDM-5-KP. Thirty-seven isolates carried various hypervirulence genes and the profiles of these genes showed high diversity. CONCLUSIONS: The predominant carbapenemase of CRKP strains from paediatric patients in Shanghai were KPC-2 and NDM-5. KL47-ST11 KPC-2-KP and KL62-ST48 NDM-5-KP were representative clonal lineages. Although not prevalent, hypervirulence associated genes have begun to spread. Active long-term surveillance should be performed in both drug resistance characteristics and virulence factors.

Fecal carriage and molecular epidemiology of carbapenem-resistant Enterobacteriaceae from outpatient children in Shanghai.

BACKGROUND: Fecal colonization with carbapenem-resistant Enterobacteriaceae (CRE) is a risk factor for bacterial translocation resulting in subsequent endogenous infections. The purpose of this study is to investigate the prevalence of CRE strains colonization in stool samples of outpatient in a tertiary pediatric hospital of Shanghai, China. METHODS: In a retrospective study, fecal samples were consecutively obtained from patients in 2016 and screening test for CRE was conducted by using home-made MacConkey agar. Antimicrobial susceptibility was determined by the broth microdilution method and ß-lactamases were characterized by polymerase chain reaction (PCR) assays and DNA sequencing. Multilocus sequence typing (MLST) was performed for the genetic relationships of the isolates. RESULTS: A total of 880 fecal samples were included for this screening test and 32 CRE strains were identified in 32 non-duplicate fecal samples from 32 children (1.3 ± 1.5 years), with a carriage rate of 3.6%. These strains mainly distributed in Klebsiella pnuemoniae (37.5%) and Escherichia coli (37.5%). All CRE strains showed high resistance to most of the routinely used antibiotics (> 90%) except for polymyxin B and tigecycline. The blaNDM gene was the major carbapenemase gene harbored by gastrointestinal CRE strains, followed by blaKPC-2, blaIMP-26, and blaIMP-4. Other ß-Lactamase genes including blaCTX-M, blaSHV, blaTEM-1, and blaDHA-1 were also detected. MLST analysis revealed that various sequence types (STs) were detected in these strains, with ST11 and ST37 being more prevalent in K.pneumoniae and ST101 in E.coli. CONCLUSIONS: This study revealed the prevalence of CRE fecal carriage in children from outpatient and urgent implementation of infection control measure should be conducted to limit the spread of CRE strains.

Epidemiology Characteristics of Streptococcus pneumoniae From Children With Pneumonia in Shanghai: A Retrospective Study.

Background:Streptococcus pneumoniae is the most common pathogen causing death in children under 5 years old. This retrospective surveillance aimed to analyze serotype distribution, drug resistance, virulence factors, and molecular characteristics of pneumonia isolates from children in Shanghai, China. Methods: A total of 287 clinical pneumococcal isolates were collected from January to December in 2018 and were divided into community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HAP) two groups according to where someone contracts the infection. All isolates were serotyped by multiplex sequential PCR and antimicrobial susceptibility testing was performed using E-test or disk diffusion method. The molecular epidemiology was analyzed using multilocus sequence typing and seven housekeeping genes were sequenced to identified the sequence types (STs). In addition, we investigated the presence of virulence genes via PCR. Results: The most common serotypes were 19F, 6A, 19A, 23F, 14, and 6B, and the coverage rates of the 7-, 10- and 13-valent pneumococcal conjugate vaccines were 58.9, 58.9, and 80.5%, respectively. More PCV13/non-PCV7 serotypes and higher rate of penicillin non-susceptible S. pneumoniae were seen in HAP. Molecular epidemiological typing showed a high level of diversity and five international antibiotic-resistant clones were found, including Taiwan19F-14, Spain23F-1, Spain6B-2, Taiwan23F-15 and Sweden15A-25. No significant difference was observed in the presence of virulence genes among the isolates obtained from CAP and HAP. All of the S. pneumoniae isolates carried lytA, ply, psaA, pavA, spxB, htrA, and clpP, and the carriage rate of nanA and piaA were 96.2 and 99.0%. Conversely, cps2A, cbpA, and pspA were present in 33.8-44.3% of the isolates. Conclusions: Serotype changes and emerging multidrug-resistant international clones were found in current study. lytA, ply, psaA, pavA, spxB, htrA, and clpP may be good protein vaccine candidates. Long-term high-quality surveillance should be conducted to assess impact and effectiveness brought by vaccines, and provide a foundation for prevention strategies and vaccine policies.