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ABSTRACT: Objectives: The blaNDM gene was prevalent among children and became the predominant cause of severe infection in infants and children. This study aimed to investigate the epidemiology and molecular characteristics of blaNDM in Enterobacteriaceae among children in China. Methods: Carbapenem-resistant Enterobacteriaceae (CRE) were collected in the Children's Hospital of Fudan University from January 2016 to December 2022. Five carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48) were screened by PCR method. Multilocus sequence typing (MLST) was conducted for phylogenetic analyses. blaNDM-carrying plasmids were typed by PCR-based Incompatibility (Inc) typing method. Moreover, plasmid comparison was performed with 213 publicly available IncX3 plasmids. Results: A total of 330 CRE strains were enrolled, 96.4% of which carried carbapenemase genes. blaNDM gene accounted for 64.8% (214 strains) and included four variants, including blaNDM-1 (59.8%), blaNDM-5 (39.3%), blaNDM-7 (0.5%), and blaNDM-9 (0.5%). There were no predominant MLST lineages of blaNDM carrying strains. IncX3 was the major plasmid carrying blaNDM-1 (68.0%) and blaNDM-5 (72.6%) and was dominant in blaNDM-Klebsiella penumoniae (79.8%), blaNDM-Escherichia coli (58.2%), and blaNDM-Enterobacter cloacae (61.0%), respectively. Most (79.0%) clinical IncX3 plasmids in the world carried blaNDM, and the prevalence of blaNDM in IncX3 plasmids was more common in China (95.8%) than other countries (58.1%, P

ObjectivesTo summarize the clinical characteristics, outcomes and identify risk factors of Acinetobacter baumannii (AB) meningitis in children.MethodsThis was a single-center, retrospective study. Children hospitalized between January 2016 and December 2021 who were diagnosed with AB meningitis were included. The clinical characteristics and outcomes were reviewed. Risk factors were determined using univariate analyses (chi-square and Mann-Whitney U tests).ResultsSeventeen patients were included; 15 cases were secondary to neurosurgery, and two were neonates with primary bacterial meningitis. Common symptoms included fever, convulsions and nervous system abnormalities. Cerebrospinal fluid (CSF) tests typically showed increased white blood cell counts dominated by neutrophils, reduced glucose levels and elevated protein levels. Ten patients were successfully treated (successful treatment [ST] group); seven had failed treatment (failed treatment [FT] group). Univariate analyses revealed that mechanical ventilation, routine white cell counts in the peripheral blood, procalcitonin, protein in the CSF, septic shock and carbapenem-resistant AB (CRAB) differed significantly between the groups.ConclusionAB meningitis in children has a high mortality rate. FT was associated with mechanical ventilation, septic shock, CRAB, lower peripheral leukocyte counts, higher protein levels in the CSF and procalcitonin. Larger studies are needed to identify independent risk factors for adverse outcomes.

BackgroundPertussis is a highly contagious respiratory illness mainly caused by Bordetella pertussis (BP). Bordetella parapertussis (BPP) can induce symptoms compatible with pertussis, but has been underdiagnosed and underreported. The current pertussis vaccines offer low protection against BPP. Herein, we aim to reveal the epidemiology and genomic evolution of BPP in Shanghai, China.MethodsChildren diagnosed with BPP infection from January 2017 to December 2022 in Shanghai, China were enrolled. We performed antimicrobial susceptibility testing (AST), multiple locus variable-number tandem repeat analysis (MLVA), and whole genome sequencing (WGS) analysis. A total of 260 international BPP genomes were chosen for comparison to investigate the genomic diversity and phylogenetic characteristics of Chinese strains within a global context.ResultsSixty patients were diagnosed with BPP infection by culture, with the positive ratio of 3.5‰ (60/17337) for BPP in nasopharyngeal swap samples. The average age of patients was 4.5 ± 0.3 years. BPPs contained four MLVA types including MT6 (65.0%), MT4 (26.7%), untype-1 (6.7%) and MT5 (1.7%), and none of strains showed resistance to macrolides. All strains carried virulence genotype of ptxP37/ptxA13/ptxB3/ptxC3/ptxD3/ptxE3/fim2-2/fim3-10. MT4 and MT5 strains carried prn54, whereas MT6 and untype-1 BPPs expressed prn101. We identified two outbreaks after 2020 caused by MT4 and MT6 strains, each corresponding to distinct WGS-based phylogenetic lineages. The MT4-lineage is estimated to have originated around 1991 and has since spread globally, being introduced to China between 2005 and 2010. In contrast, the MT6-lineage was exclusively identified in China and is inferred to have originated around 2002.ConclusionWe revealed the genomic diversity of BPPs circulating in Shanghai, China, and reported the outbreaks of MT6 and MT4 BPPs after 2020. This is the first report on the emergence and regional outbreak of MT6 BPPs in the world, indicating that continuous surveillance on BPPs are thus required.

Proton exchange membrane water electrolysis (PEMWE) with high‐purity H2 and O2 products and swift response to electricity fluctuation is of great interest for renewable energy, chemical and pharmaceutical industries. Ruthenium oxide shows promise as an alternative to iridium oxide catalysts in PEMWE but suffers from severe anodic corrosion. Herein, a pluralistic electronic structure modulation approach is presented to address the instability issue of Ru, by in situ growing MnxRu1−xO2 solid solution on MnO2, coated carbon fibers (MnxRu1−xO2/MnO2/CFs). Due to higher ion electronegativity, Mn dopants in the MnxRu1−xO2 solid solution accept electrons, activating the Ru site. Simultaneously, the MnO2 support donates electrons to prevent Ru site overoxidation and dissolution due to its lower work function than the MnxRu1−xO2 solid solution. As a result, the MnxRu1−xO2/MnO2/CFs catalyst exhibits a low overpotential of 161 mV at 10 mA cm−2 and a remarkable stability exceeding 600 h. Profiting by its improved oxygen evolution reaction (OER) kinetic activity, the MnxRu1−xO2/MnO2/CF‐based PEMWE shows a low cell voltage of 1.9 V at 2 A cm−2, and stably operate at current density of 500 mA cm−2 for 24 h. This work shows the potential of the pluralistic electronic structure modulation to boost activity and stability of Ru‐based acidic OER electrocatalysts.

Background: The increasing prevalence of antibiotic-resistant Helicobacter pylori strains poses a significant threat to children's health. This study investigated antibiotic resistance rates in Helicobacter pylori strains isolated from children in Shanghai and analyzed the presence of virulence genes in these strains. Methods: We obtained 201 Helicobacter pylori strains from pediatric patients with upper gastrointestinal symptoms who underwent gastrointestinal endoscopy between 2019 and 2022. Subsequently, we performed antibiotic susceptibility tests and virulence gene PCR assays on these strains. Results: Helicobacter pylori resistance rates of 45.8%, 15.4%, 1.0%, and 2.5% were detected for metronidazole, clarithromycin, amoxicillin, and levofloxacin, respectively. Among all isolates, 64.7% exhibited resistance to at least one antibiotic. Resistance to metronidazole and clarithromycin increased from 2019 to 2022. The predominant vacA gene subtype was vacA s1a/m2. The prevalence of vacA m2 and dupA exhibited an upward trend, while oipA presented a decreasing trend from 2019 to 2022. The prevalence of dupA was significantly higher in gastritis than peptic ulcer disease, and in non-treatment compared to treatment groups. Conclusions: Helicobacter pylori antibiotic resistance remains high in children and has risen in recent years. Therefore, the increasing use of metronidazole and clarithromycin requires increased monitoring in children. No association was observed between antibiotic resistance and virulence gene phenotypes.

Resurgence and spread of macrolide-resistant Bordetella pertussis (MRBP) threaten global public health. We collected 283 B. pertussis isolates during 2016–2022 in Shanghai, China, and conducted 23S rRNA gene A2047G mutation detection, multilocus variable-number tandem-repeat analysis, and virulence genotyping analysis. We performed whole-genome sequencing on representative strains. We detected pertussis primarily in infants (0–1 years of age) before 2020 and older children (>5–10 years of age) after 2020. The major genotypes were ptxP1/prn1/fhaB3/ptxA1/ptxC1/fim2–1/fim3–1 (48.7%) and ptxP3/prn2/fhaB1/ptxA1/ptxC2/fim2-1/fim3-1 (47.7%). MRBP increased remarkably from 2016 (36.4%) to 2022 (97.2%). All MRBPs before 2020 harbored ptxP1, and 51.4% belonged to multilocus variable-number tandem-repeat analysis type (MT) 195, whereas ptxP3-MRBP increased from 0% before 2020 to 66.7% after 2020, and all belonged to MT28. MT28 ptxP3-MRBP emerged only after 2020 and replaced the resident MT195 ptxP1-MRBP, revealing that 2020 was a watershed in the transformation of MRBP.

Abstract Argonaute proteins (Agos) bind short nucleic acids as guides and are directed by them to recognize target complementary nucleic acids. Diverse prokaryotic Agos (pAgos) play potential functions in microbial defense. The functions and mechanisms of a group of full-length yet catalytically inactive pAgos, long-B pAgos, remain unclear. Here, we show that most long-B pAgos are functionally connected with distinct associated proteins, including nucleases, Sir2-domain-containing proteins and trans-membrane proteins, respectively. The long-B pAgo-nuclease system (BPAN) is activated by guide RNA-directed target DNA recognition and performs collateral DNA degradation in vitro. In vivo, the system mediates genomic DNA degradation after sensing invading plasmid, which kills the infected cells and results in the depletion of the invader from the cell population. Together, the BPAN system provides immunoprotection via abortive infection. Our data also suggest that the defense strategy is employed by other long-B pAgos equipped with distinct associated proteins.

Abstract Objective To investigate the characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) in bone and joint infection (BJI) among children. Methods A total of 338 patients diagnosed with BJI from 2013 to 2022 in Children’s Hospital of Fudan University were enrolled. Demographic information, microbiology culture results and laboratory findings, including white blood counts (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and erythrocyte sedimentation rate (ESR) were collected and analyzed. MRSA was confirmed by antimicrobial susceptibility testing. Other MRSA-caused infections were randomly selected for comparison. Twenty-three virulence and antimicrobial resistance (AMR) genes were screened for MRSA strains. Multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing were performed using PCR amplification and sequencing. Results Of the identified pathogens in BJI, MRSA accounted for 21.0% (47/224). Patients with BJI had high levels of initial CRP, white blood cell count (WBC) and IL-6. ST59 (43.9%) and t437 (37.6%) were the main MRSA subtypes isolated from the children. The major genotypes in BJI were ST59-t437 (29.8%) and ST22-t309 (14.9%), with high carriage of hemolysins including hla (94.4–100%), hlb (66.2–93.3%), and hld (100%). Notably, Panton–Valentine leukocidin (pvl) had a high prevalence (53.3%) in ST22-t309-MRSA. Other virulence genes including tst, seg and sei were more commonly detected in ST22-t309-MRSA (40.0–46.7%) than in ST59-t437-MRSA (4.2–9.9%). High-carriage AMR genes in MRSA included aph(3ʹ)/III (66.7–80%), ermB (57.5–73.3%) and ermC (66.7–78.9%). MRSA presented high-resistance to erythromycin (52.0–100%) and clindamycin (48.0–92.5%), different genotypes displayed variation in their susceptibilities to antibiotics. Conclusions The major MRSA genotype in BJI was ST59-t437, followed by ST22-t309, with a higher prevalence of the pvl gene. Continuous surveillance of pvl-positive ST22-t309-MRSA in pediatric BJI infections is thus required.

Objectives: To reveal the clinical and molecular characteristics of Bordetella pertussis (BP) prevalent in Shanghai, China. Methods: A total of 9430 children with suspected pertussis from 2021 to 2022 were included, and nasopharyngeal swab samples were collected for polymerase chain reaction detection, culture, antimicrobial susceptibility testing, and 23S rRNA gene A2047G detection. BP strains were typed using multilocus variable-number tandem-repeat analysis and virulence genotyping. Results: Of 9430 cases, 5.1% and 1.6% were confirmed by polymerase chain reaction and culture, respectively. Infants (aged 6-10 years (10.8∼21.7%). Macrolide-resistant BP (MRBP) accounted for 89.3%, and all carried the A2047G mutation. There were six multilocus variable-number tandem-repeat analysis types (MTs), including MT28 (62.0%), MT195 (20%), MT27 (10.0%), MT104 (4.7%), MT55 (2.7%), and MT32 (0.7%). BP strains with pertussis toxin (ptx)P3/(pertactin) prn2/ptxC2/ptxA1/(fimbrial proteins) fim2-1/fim3-1, including MT27, MT28, and MT32, accounted for 72.7%, among which MT27 and MT32 were macrolide-sensitive BP, whereas most (94.6∼100%) of MT28 were MRBP. Strains harboring ptxP1/prn1/ptxC1/ptxA1/fim2-1/fim3-1, including MT55, MT104, and MT195, belonged to macrolide-sensitive BP. Conclusion: The emergence and spread of MT28 ptxP3-MRBP was first reported in China, highlighting the importance of continuous surveillance of ptxP3-MRBP to prevent its potential circulation.

Background: We isolated the carbapenemase-producing Enterobacteriaceae (CPE) strains from children during 2016–2021 in Shanghai, China and investigated the antimicrobial resistance, molecular and epidemiological features of these isolates. Methods: Antimicrobial susceptibility tests were performed to confirm the carbapenem resistance. Carbapenemase production was assessed by the rapid phenotypic identification of five major carbapenemases (KPC, NDM, VIM, IMP, and OXA-48), which were further confirmed by PCR amplification and sequencing. Multilocus sequence typing (MLST) was conducted for phylogenetic analyses. Results: A total of 320 CPE strains were collected from 2016 to 2021, consisting of carbapenemase-producing Klebsiella pneumoniae (CP-Kpn, 55.0%), Escherichia coli (CP-Eco, 24.5%) and Enterobacter cloacae (CP-Ecl, 20.4%) and others (2, 0.1%). NDM was the primary carbapenemase (67.6%) in children, followed by KPC(26.4%), IMP(5.3%) and OXA-48 (0.6%). The minimum inhibitory concentration (MIC) for imipenem has been increasing from 2016 to 2021. NDM and KPC isolates are high resistant while IMP strains show the lower resistant to imipenem. Invasive infection accounted for 10.7% of CPE-related infections and was mainly caused by CP-Kpn (70.6%). NDM-Kpn was detected in 51.8% of infants (70.8% of neonates), while KPC-Kpn was mainly isolated from non-infants (56.3%∼64.3%). ST11 was the primary clone (64.6%) of KPC-Kpn and presented an increasing trend from 2016 to 2021. Conclusion: NDM is widely prevalent and transfers among CPE strains in children. NDM-Kpn shows the most serious threat to infants, especially to neonates. High-risk clone of ST11 KPC-Kpn should be paid more attention and monitored continuously in children.

Here the authors harness the on-chip integration of Jones matrix metasurfaces to demonstrate an ultra-compact approach to access and manipulate the optical spin states of vertical cavity surface-emitting lasers (VCSELs) with previously unattainable phase controllability.

PurposeTo investigate the mechanisms of Klebsiella pneumoniae-induced pyogenic liver abscess (PLA).MethodsForty-three K. pneumoniae strains from PLAs and 436 from non-PLAs were collected. Their differences were compared for virulence genes and factors, sequence types, and serotypes. Virulence genes wzi, wzy-K1, and wzi+wzy-K1 were deleted in K. pneumoniae NTUH-K2044. Various analyses, such as transmission electron microscopy, neutrophil killing tests, and mouse lethality tests, were used to confirm the consequent changes.ResultsDifferences were found between K. pneumoniae strains from PLA and non-PLA samples for virulence genes and factors, including metabolism genes (allS and peg-344), capsular polysaccharide (CPS)-synthesis channel gene (wzy-K1), CPS-regulating genes (p-rmpA, p-rmpA2, and c-rmpA), and siderophore genes (iucA and iroN). When wzy-K1 was positive, the difference between PLA and non-PLA samples was only observed with c-rmpA. Δwzi, Δwzy-K1, and ΔwziΔwzy-K1 strains reverted to hypovirulence. In the Kupffer cell stimulation assay, interleukin (IL)-6, IL-12, IL-10, and transforming growth factor-β secretions were found to be equivalent in NTUH-K2044, Δwzi, Δwzy-K1, and ΔwziΔwzy-K1 groups. Lower IL-1β and higher tumor necrosis factor-α secretions were observed for Δwzi, Δwzy-K1, and ΔwziΔwzy-K1.ConclusionsHypercapsule production is the cornerstone of hypervirulence, regardless of exopolysaccharides. K1 K. pneumoniae-induced PLA may decrease core inflammatory cytokines rather than increase anti-inflammatory cytokines. Exopolysaccharides could also attenuate the inflammatory response to aid in the immune escape of K. pneumoniae.

ObjectiveTo investigate the epidemiology and infectious characteristics of Epstein-Barr virus (EBV) infection among children in Shanghai, China from 2017 to 2022.MethodsWe conducted a retrospective analysis of 10,260 inpatient patients who were subjected EBV nucleic acid testing from July 2017 to December 2022. Demographic information, clinical diagnosis, laboratory findings, etc. were collected and analyzed. EBV nucleic acid testing were performed by real-time PCR.ResultsA total of 2192 (21.4%) inpatient children were EBV-positive, with the average age of 7.3 ± 0.1 y. EBV detection was stable from 2017 to 2020 (26.9~30.1%), but showed essential decreases in 2021 (16.0%) and 2022 (9.0%). EBV was highest (>30%) detected from three quarters (Q) including 2018-Q4, 2019-Q4 and 2020-Q3. There were 24.5% of EBV coinfection with other pathogens, including bacteria (16.8%), other viruses (7.1%) and fungi (0.7%). EBV viral loads increased when coinfecting with bacteria ((142.2 ± 40.1) ×104/mL) or other viruses ((165.7 ± 37.4) ×104/mL). CRP significantly increased in EBV/fungi coinfection, while procalcitonin (PCT) and IL-6 showed remarkable increases in EBV/bacteria coinfection. Most (58.9%) of EBV-associated diseases belonged to immune disorders. The primary EBV-related diseases were systemic lupus erythematosus (SLE, 16.1%), immunodeficiency (12.4%), infectious mononucleosis (IM, 10.7%), pneumonia (10.4%) and Henoch-schonlein purpura (HSP, 10.2%). EBV viral loads were highest ((233.7 ± 27.4) × 104/mL) in patients with IM.ConclusionEBV was prevalent among children in China, the viral loads increased when coinfecting with bacteria or other viruses. SLE, immunodeficiency and IM were the primary EBV-related diseases.

Among the existing gas storage facilities, salt cavern gas storage has the advantages of high injection production efficiency, low gas cushion volume, safety, flexibility, etc. It is of great significance to speed up the construction of underground gas storage by transforming abandoned salt caverns of salt industry into underground gas storage. However, old salt cavern wells cannot be directly converted into gas storage injection and production wells, so the old wellbore must be plugged to ensure the effectiveness of plugging. Therefore, a set of plugging optimization technology for salt cavern gas storage wells is urgently needed. In this paper, a 3D finite element model of the cement plug-formation system based on cohesive element method is established for the milling and plugging of the old well in the salt cavern gas storage section. The results show that under the condition of constant gas storage pressure, a certain degree of small deformation will occur at the bottom of the cement plug after compression, resulting in the shear direction deformation of the cement plug formation cementation interface, and peeling will occur after accumulation to a certain extent. With the increase of simulation time, the length of stripping section gradually increases and tends to be stable, and reaches the limit of stripping failure length. In the process of research, the factors and laws affecting the stripping failure length were also analyzed. It was found that the stripping failure length of cement plug formation cementation interface was related to the maximum operating pressure of gas storage, cement plug length, cement plug diameter, elastic modulus, Poisson’s ratio and other factors. The research results are helpful to judge whether the milling and plugging length of the old well section is sufficient, and provide theoretical guidance for ensuring the long-term safe operation of the gas storage.

Magnesium alloy has the advantages of low density, good damping and noise reduction and good electrical conductivity. It is the lightest metal structural material in applications. However, they are easily corroded due to the low potential of magnesium alloy electrodes, which limits their wide application in industry. At present, surface coating protection technology is one of the most effective methods to improve the corrosion resistance of magnesium alloys. Graphene oxide (GO) has excellent thermal, mechanical and barrier properties, and has broad application prospects in metal protection. GO-based composite coatings can provide a good physical barrier to corrosive media and have become one of the candidate materials for anti-corrosion coatings. In this article, the solutions were proposed for the limitations of single-component GO nanosheets, such as agglomeration and poor compatibility. The preparation methods, types and corrosion protection research progress of GO composite coatings were mainly summarized and its protection mechanism was analyzed in depth. Finally, the future development trend of GO application of magnesium alloy surface corrosion protection coating were prospected. The preparation methods and types of GO composite coatings on magnesium alloys were mainly described. The research progress and corrosion protection mechanism of GO coating on magnesium alloy were summarized.

Tumor suppressor BRCA2 is known to stabilize and restart stalled DNA replication forks. Here the authors show that BRCA2 is recruited to the replication fork through its interaction with MCM10 and inhibits Primase-Polymerase-mediated repriming, lesion bypass and single strand DNA gap formation after DNA damage.

Retinal vein injection guided by microscopic image is an innovative procedure for treating retinal vein occlusion. However, the retina organization is complex, fine, and weak, and the operation scale and force are small. Surgeons’ limited operation and force-sensing accuracy make it difficult to perform precise and stable drug injection operations on the retina in a magnified field of image vision. In this paper, a 3-DOF automatic drug injection mechanism was designed for microscopic image guiding robot-assisted needle delivery and automatic drug injection. Additionally, the robot-assisted real-time three-dimensional micro-force-sensing method for retinal vein injection was proposed. Based on the layout of three FBG sensors on the hollow outer wall of the nested needle tube in a circular array of nickel-titanium alloys, the real-time sensing of the contact force between the intraoperative instrument and the blood vessel was realized. The experimental data of 15 groups of porcine eyeball retinal veins with diameters of 100–200 μm showed that the piercing force of surgical instruments and blood vessels is 5.95∼12.97 mN, with an average value of 9.98 mN. Furthermore, 20 groups of experimental measurements on chicken embryo blood vessels with diameters of 150–500 μm showed that the piercing force was 4.02∼23.4 mN, with an average value of 12.05 mN.

ObjectiveTo investigate the epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) and hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP).MethodsTotally 436 K. pneumoniae strains were collected from 7 hospitals in mainland China between 2017.01 and 2018.02. Sequence types, serotypes, antimicrobial-resistance and virulence genes were analyzed. Additionally, string test, capsule stain, Periodic Acid Schiff stain, fitness analysis, quantitative real-time PCR and mouse lethality test were also performed. Molecular combinations were used to screen putative blaKPC(+)-HvKP and Hv-blaKPC(+)-KP, followed by the confirmation of mouse lethality test.ResultsDiverse detection rates were found for the virulence genes, ranging from c-rmpA (0.0%) to entB (100.0%). According to the molecular criteria, 127, 186, 9 and 26 strains were putatively denoted as HvKP, blaKPC(+)-KP, blaKPC(+)-HvKP and Hv-blaKPC(+)-KP. Mouse lethality test confirmed 2 blaKPC(+)-HvKP strains (JS184 and TZ20) and no Hv-blaKPC(+)-KP. JS184 showed K2 serotype, thin capsule, positive exopolysaccharid and string test. TZ20 presented K20 serotype, thin capsule, negative exopolysaccharide and string test. Compared with the positive control NTUH-K2044, equal galF expression and growth curves were confirmed for JS184 and TZ20.ConclusionsMolecular determination of CR-HvKP and Hv-CRKP brings remarkable bias compared with mouse lethality test. The exact prevalence of CR-HvKP is less than 1.0%, which of Hv-CRKP is much lower.

A novel semi-solid extrusion shear process was proposed based on the idea of "process coupling and shortening process", which can improve the comprehensive mechanical properties by grain refinement. The casting process and solidification process of AZ31 semi-solid forming process were simulated via Anycasting software. The appropriate extrusion parameters were selected by comparing the results of simulation and experiment. The results show that in the deformation zone, the nucleation of AZ31 is promoted by dendrite fragmentation and pressure, leading to the achievement of a fine and uniform structure. The presence of the liquid phase is beneficial to coordinating the deformation during extrusion, reducing the effect of slip and twining on the texture, and thus the extrusion texture is weakened. The maximum basal texture strength is only 5.3 when the shear angle is 180°. Shear angle can further refine grains and improve comprehensive mechanical properties.The best mechanical properties are obtained at the shear angle of 150° with yield strength of 222 MPa, tensile strength of 309 MPa and elongation of 8%.

The SiO2/SiNx dielectric film stacks deposited by inductively coupled plasma chemical vapor deposition (ICP-CVD) are employed on the top of the oxide-confined vertical-cavity surface-emitting lasers (VCSELs). The reflecting mirror characteristics of the dielectric films are measured with varying numbers of pairs from 4 to 12. The prepared devices have low threshold current of 0.3 mA, single-mode peak power of 1.4 mW at room temperature. The thermal resistance of the device depending on ambient temperature is estimated according to the relationship of wavelength shift and dissipated power, allowing us to extract the actual temperature in active region and the temperature dependence of the output characteristics of the VCSEL. The beam property of the device is characterized by the far field pattern (FFP). Depending on the drive current, the average divergence angles of the output beam estimated from the full-width-half-maximum (FWHM) of the FFP varies between 20.4° and 21.2°. Furthermore, polarization-controlled single mode emission is achieved by introducing a built-in grating into the VCSEL with orthogonal polarization suppression ratio (OPSR) around 19 dB.

Abstract Background Hereditary spherocytosis (HS) is the most common haemolytic anaemia caused by congenital membrane defects of red blood cells. The name derives from the presence of spherical red blood cells in the peripheral blood. Clinical manifestations of HS are anaemia, haemolytic jaundice, and large spleen, and infection can worsen the condition, often with cholelithiasis. HS is mainly caused by abnormal functions of the products of six genes. Splenectomy is the main treatment for HS. Case presentation Half a day after birth, the proband exhibited HS-related symptoms, with progressive aggravation. Routine examination in the outpatient department showed an increase in white blood cells and a decrease in red blood cells. His mother had HS and a partial splenectomy. We suspected that the infant might also have HS. Genomic DNA samples were extracted from the three members of the HS trio pedigree, and genomic whole-exome sequencing (WES) was performed. The three DNA samples were amplified by polymerase chain reaction (PCR), followed by Sanger sequencing to identify mutation sites. A novel nonsense heterozygous mutation, c.790C > T (p. Gln264Ter), in the ANK1 gene, which causes premature termination of translation, was found in this Chinese family with autosomal dominant HS. Conclusions This de novo nonsense mutation can cause the onset of HS in early childhood, with severe symptoms. Expanding the ANK1 genotype mutation spectrum will lay a foundation for the further application of mutation screening in genetic counselling.

Abstract Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol（RES）in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES‐mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial‐mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway.

ABSTRACT Consolidation is one complication of pediatric severe community-acquired pneumonia (SCAP) that can respond poorly to conservative medical treatment. We investigated the pathogens that cause pediatric SCAP including cases with persistent consolidation that need bronchoscopy intervention. Alveolar lavage fluid (ALF) samples collected from cases admitted to Children’s Hospital of Fudan University with SCAP during January 2019 to March in 2019 were retrospectively tested by the RespiFinder 2SMART multiplex PCR (multi-PCR) assay targeting 22 respiratory pathogens. A total of 90 cases and 91 samples were enrolled; 80.0% (72/90) of the cases had pulmonary consolidation and/or atelectasis. All samples were positive with targeted pathogens tested by multi-PCR, and 92.3% (84/91) of the samples were co-detected with pathogens. Mycoplasma pneumoniae (MP) and adenovirus (ADV) as the two dominant pathogens, with the positive rates of 96.7% (88/91) and 79.1% (72/91), respectively. Most of the samples were positive with MP and ADV simultaneously. As a control, 78.0% (71/91) of the samples were positive by conventional tests (CT), in which MP had the detection rate of 63.9% (55/86) by a traditional real-time PCR assay, while ADV were positive in 13.1% (12/91) of the samples by a direct immunofluorescence assay (DFA). In cases with persistent pulmonary consolidation, the positive rates of pathogens by multi-PCR and CT were 100% (72/72) and 81.9% (59/72), respectively. There were no significant differences of MP or ADV positive rates between cases with and without pulmonary consolidation. MP and ADV most prevalent in pediatric SCAP cases required fiberscope intervention, and presented with coinfections dominantly. IMPORTANCE Pathogens that cause pediatric severe community-acquired pneumonia (SCAP) requiring bronchoscopy intervention are understudied. Through this study, we explore the etiology of SCAP form alveolar lavage fluid (ALF) samples by the RespiFinder 2SMART multi-PCR assay. It is observed that high mixed detection rates of Mycoplasma pneumoniae and adenovirus in ALF samples collected from hospitalized SCAP children experienced bronchoscopy intervention. Eighty percent of the cases had pulmonary consolidation and/or atelectasis. The presence of possible coinfection of these two pathogens might contribute to poor clinical anti-infection response. The results of this study might be helpful for the selection of clinical strategies for the empirical treatment of such pediatric SCAP cases.

The tribological properties of garaphene and graphene oxide (GO) as water based additives were investigated for AZ31 Magnesium alloy cold rolling. The morphology and composition of surfaces were characterized by field emission scanning electron microscopy(FESEM) and Raman spectrum. The lubricating mechanism of graphene and graphene oxide(GO) as water-based additives was explored. The results indicate that the best tribological response of the magnesium alloy/steel pairs evaluated is obtained when GO and graphene at a concentration of 0.5%(mass fraction) is added to water. The friction coefficients of graphene nanofluids and GO nanofluids are 0.132 and 0.038, and the wear volumes are 23.1 mm3 and 2.59 mm3. Furthermore, the cold-rolling tests show that the application of GO nanofluids leads to a significant reduction in the rolling force and an improvement in the surface quality of sheets. Under the same testing conditions, the lubricating performance of GO nanofluids are superior to graphene nanofluids, which attributes to the superior dispersion in the water and prominent wetting of the GO nanofluids on the magnesium alloy surface.

ABSTRACTKlebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) have disseminated worldwide and emerged as major threats to public health. Of epidemiological significance, the international pandemic of KPC-KP is primarily associated with CG258 isolates and blaKPC-IncF plasmids. CRISPR-Cas system is an adaptive immune system that can hinder gene expansion driven by horizontal gene transfer. Because of blaKPC-IncF plasmids are favored by CG258 K. pneumoniae, it was of interest to examine the co-distribution of CRISPR and blaKPC-IncF plasmids in such isolates. We collected 459 clinical K. pneumoniae isolates in China and collected 203 global whole-genome sequences in GenBank to determine the prevalence of CRISPR-Cas systems. We observed that CRISPR-Cas system was significantly scarce in the CG258 lineage and blaKPC-positive isolates. Furthermore, the results of conjugation and plasmid stability assay fully demonstrated the CRIPSR-Cas system in K. pneumoniae could effectively hindered blaKPC-IncF plasmids invasion and existence. Notably, most blaKPC-IncF plasmids were also proved to be good targets of CRISPR owing to carry matched and functional protospacers and PAMs. Overall, our work suggests that type I-E CRISPR-Cas systems could impact the spread of blaKPC in K. pneumoniae populations, and the scarcity of CRISPR-Cas system was one of potential factors leading to the propagation of blaKPC-IncF plasmids in CG258 K. pneumoniae.

We aimed to examine the association of CSF tumor necrosis factor-alpha (TNFα) with conversion from mild cognitive impairment (MCI) to dementia. At baseline, there were a total of 129 participants with MCI in this study. The association of CSF TNFα levels with the incidence of dementia were evaluated using Cox proportional hazards regression analysis adjusted for potential confounders. Individuals were categorized into groups based on the CSF TNFα tertiles. Compared to the low group (the reference group), the intermediate group progressed more rapidly to dementia [HR (95% CI) = 2.2 (1.15-4.1); p = 0.016] after adjusting for other covariates. However, the high group did not progress faster than the low group [HR (95% CI) = 1.5 (0.79-2.8); p = 0.214]. Our study suggested a potential non-relationship between CSF TNFα levels and the risk of development of dementia among MCI older people.

ABSTRACT The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial resistance (AMR) in children. Clinical bacterial isolates were collected from 11 tertiary care children’s hospitals in China in 2016 to 2020. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer method or automated systems, with interpretation according to the Clinical and Laboratory Standards Institute 2019 breakpoints. A total of 288,377 isolates were collected, and the top 10 predominant bacteria were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. In 2020, the coronavirus disease 2019 (COVID-19) pandemic year, we observed a significant reduction in the proportion of respiratory tract samples (from 56.9% to 44.0%). A comparable reduction was also seen in the primary bacteria mainly isolated from respiratory tract samples, including S. pneumoniae, H. influenzae, and S. pyogenes. Multidrug-resistant organisms (MDROs) in children were commonly observed and presented higher rates of drug resistance than sensitive strains. The proportions of carbapenem-resistant K. pneumoniae (CRKP), carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and methicillin-resistant S. aureus (MRSA) strains were 19.7%, 46.4%%, 12.8%, and 35.0%, respectively. The proportions of CRKP, CRAB, and CRPA strains all showed decreasing trends between 2015 and 2020. Carbapenem-resistant Enterobacteriaceae (CRE) and CRPA gradually decreased with age, while CRAB showed the opposite trend with age. Both CRE and CRPA pose potential threats to neonates. MDROs show very high levels of AMR and have become an urgent threat to children, suggesting that effective monitoring of AMR and antimicrobial stewardship among children in China are required. IMPORTANCE AMR, especially that involving multidrug-resistant organisms (MDROs), is recognized as a global threat to human health; AMR renders infections increasingly difficult to treat, constituting an enormous economic burden and producing tremendous negative impacts on patient morbidity and mortality rates. There are many surveillance programs in the world to address AMR profiles and MDRO prevalence in humans. However, published studies evaluating the overall AMR rates or MDRO distributions in children are very limited or are of mixed quality. In this study, we showed the bacterial epidemiology and resistance profiles of primary pathogens in Chinese children from 2016 to 2020 for the first time, analyzed MDRO distributions with time and with age, and described MDROs’ potential threats to children, especially low-immunity neonates. Our study will be very useful to guide antiinfection therapy in Chinese children, as well as worldwide pediatric patients.

The computational material science based on molecular dynamics method is critical for the investigation of the micro-nano scale plastic deformation, which helps to clarify the competition relationship between different plastic deformation mechanisms of magnesium alloys.The mechanism of slip, twinning and grain boundary sliding in magnesium alloys was summarized; the basic principles of molecular dynamics and the potential functions commonly applied to the hexagonal close-packed structure metals were briefly introduced. Moreover,the research progress of plastic deformation mechanism of Mg alloys based on the molecular dynamics was mainly analyzed. Based on the main problems mentioned above, it was pointed out that the development of high-precision potential function for magnesium alloy multiple systems and how to achieve the relationship of multiple scales will be the focused directions in the further research.

The tribological properties of garaphene and graphene oxide (GO) as water based additives were investigated for AZ31 Magnesium alloy cold rolling. The morphology and composition of surfaces were characterized by field emission scanning electron microscopy(FESEM) and Raman spectrum. The lubricating mechanism of graphene and graphene oxide(GO) as water-based additives was explored. The results indicate that the best tribological response of the magnesium alloy/steel pairs evaluated is obtained when GO and graphene at a concentration of 0.5%(mass fraction) is added to water. The friction coefficients of graphene nanofluids and GO nanofluids are 0.132 and 0.038, and the wear volumes are 23.1 mm3 and 2.59 mm3. Furthermore, the cold-rolling tests show that the application of GO nanofluids leads to a significant reduction in the rolling force and an improvement in the surface quality of sheets. Under the same testing conditions, the lubricating performance of GO nanofluids are superior to graphene nanofluids, which attributes to the superior dispersion in the water and prominent wetting of the GO nanofluids on the magnesium alloy surface.

ObjectiveTo investigate the overall distributions of key virulence genes in Klebsiella pneumoniae, especially the hypervirulent blaKPC-positive K. pneumoniae (Hv-blaKPC(+)-KP).MethodsA total of 521 complete genomes of K. pneumoniae from GenBank were collected and analyzed. Multilocus sequence typing, molecular serotyping, antibiotic-resistance, virulence genes and plasmid replicon typing were investigated.ResultsPositive rates of virulence genes highly varied, ranging from 2.9 (c-rmpA/A2) to 99.6% (entB). Totally 207 strains presented positive fimH, mrkD, entB and wzi and 190 showed positive fimH, mrkD, entB, irp2 and wzi, which were the two primary modes. A total of 94, 165 and 29 strains were denoted as hypervirulent K. pneumoniae (HvKP), blaKPC(+)-KP and Hv-blaKPC(+)-KP. ST11 accounted for 17 among the 29 Hv-blaKPC(+)-KP strains; Genes iucA, p-rmpA2 and p-rmpA were positive in 28, 26 and 18 Hv-blaKPC(+)-KP strains respectively. Among the 29 Hv-blaKPC(+)-KP strains exhibiting four super clusters from GenBank, IncHI1B plasmids carrying virulence genes and IncFII ones with blaKPC were responsible for both 23 strains respectively.ConclusionsPositive rates of virulence genes vary remarkably in K. pneumoniae. Genes iucA, p-rmpA2 and p-rmpA were primary ones inducing Hv-blaKPC(+)-KP. IncHI1B plasmids carrying virulence genes and IncFII ones with blaKPC constitute the primary combination responsible for Hv-blaKPC(+)-KP. The making of Hv-blaKPC(+)-KP is mostly via blaKPC(+)-KP acquiring another plasmid harboring virulence genes.

Trans-resveratrol (RES) exhibits a wide range of biological activities. Various methodological approaches have been established to improve the pharmacokinetic properties of RES. Moreover, additional in vivo studies are required to support clinical application. In this study, RES/HP-β-CD (RHSD) inclusion complex was prepared and characterized by FTIR, PXRD, DSC and NMR data. The effect and potential mechanism of RHSD against cervical cancer were investigated in a mouse xenograft tumor model by qPCR assay, Western blot assay, and immunohistochemical assay. Results showed that RHSD significantly decreased tumor growth compared with free RES, while the effect of preventing tumor growth was more prominent in vivo. Notably, RHSD could inhibit tumor development by suppressing the expression of HPV E6 and E7 oncogenes and upregulating P53 and Rb1 protein in cervical cancer. These findings demonstrated that RHSD was safe and potential for development of a new oral administration drug to treat cervical cancer.

Abstract Background Lysinibacillus sphaericus has been widely used in integrated mosquito control program and it is one of the minority bacterial species unable to metabolize carbohydrates. In consideration of the high genetic conservation at genomic level and difficulty of genetic horizontal transfer, it is hypothesized that effective restriction-modification (R-M) systems existed in mosquitocidal L. sphaericus. Results In this study, six type II R-M systems including LspC3–41I were predicted in L. sphaericus C3–41 genome. It was found that the cell free extracts (CFE) from this strain shown similar restriction and methylation activity on exogenous Bacillus/Escherichia coli shuttle vector pBU4 as the HaeIII, which is an isoschizomer of BspRI. The Bsph_0498 (encoding the predicted LspC3–41IR) knockout mutant Δ0498 and the complement strain RC0498 were constructed. It was found that the unmethylated pBU4 can be digested by the CFE of C3–41 and RC0498, but not by that of Δ0498. Furthermore, the exogenous plasmid pBU4 can be transformed at very high efficacy into Δ0498, low efficacy into RC0498, but no transformation into C3–41, indicating that LspC3–41I might be a major determinant for the genetic restriction barrier of strain C3–41. Besides, lspC3–41IR and lspC3–41IM genes are detected in other two strains besides C3–41 of the tested 16 L. sphaericus strains, which all belonging to serotype H5 and MLST sequence type (ST) 1. Furthermore, the three strains are not horizontal transferred, and this restriction could be overcome by in vitro methylation either by the host CFE or by commercial methytransferase M. HaeIII. The results provide an insight to further study the genetic restriction, modification and evolution of mosquitocidal L. sphaericus, also a theoretical basis and a method for the genetic manipulations of L. sphaericus. Conclusions LspC3–41I is identified as the major determinant for the restriction barrier of L. sphaericus C3–41. Only three strains of the tested 16 L. sphaericus strains, which all belonging to serotype H5 and ST1 by MLST scheme, contain LspC3–41I system. Two different methods can be used to overcome the restriction barrier of the three isolates to get transformants efficiently: 1) to methylate plasmid DNA prior to the electroporation; and 2) to delete the major restriction endonuclease encoding gene lspC3–41IR.

The elevated temperature mechanical properties and fracture mechanisms of as-aged ZM61-xSn(x=0,6,8,10, mass fraction/%)alloys are investigated by optical microscope(OM), X-ray diffraction(XRD), scanning electron microscope(SEM) and high temperature tensile test. The results show that the phase compositions of ZM61-xSn(x=6,8,10)alloys are α-Mg,α-Mn,MgZn2 and Mg2Sn phases. The Sn element can refine the microstructure, improve the high temperature tensile strength, but deteriorate the elongation of ZM61 alloy. The ultimate tensile strength of ZM61-xSn(x=6,8,10) alloys with tensile test at 300℃ are 149,140, 145MPa, compared with ZM61 alloy which is carried out tensile test at the same temperature, the tensile strength increased 26%,17% and 23%, respectively. The elongation of ZM61-xSn(x=0,6,8,10)alloys with tensile test at 300℃ are 39.95%,5.65%,7.01% and 6.33%. The tensile temperature exerts dominating effect for ZM61-xSn(x=6,8,10)alloys on the fracture mechanism. As tensile temperature lower than 220℃, the alloys show transgranular fracture characteristics. The alloys show intergranular fracture characteristics when the tensile temperature is higher than 220℃.

Since the measurement of mechanical sealing film thickness and just-lift-off time is very difficult, the sealing film condition monitoring method based on acoustic emission signal is proposed. The mechanical seal acoustic emission signal present obvious characteristics of time-varying nonlinear and pulsating. In this paper, the acoustic emission signal is used to monitor the seal end faces just-lift-off time and friction condition. The acoustic emission signal is decomposed by empirical mode decomposition into a series of intrinsic mode function with independent characteristics of different time scales and different frequency band. The acoustic emission signal only generated by end faces friction is obtained by eliminating the false intrinsic mode function components. The correlation coefficient of acoustic emission signal and Multi-scale Laplace Wavelet is calculated. It is proved that the maximum frequency (8000 Hz) of the correlation coefficient is appeared at the spindle speed of 300 rpm. And at this time (300 rpm) the end faces have just lifted off. By a set of mechanical oil seal running test, it is demonstrated that this method could accurately identify mechanical seal end faces just-lift-off time and friction condition.

For the problem of the determination of lift-off position and the measurement of end face thickness for mechanical seal more difficult, the method based on acoustic emission signal end face lift-off condition monitoring technology for mechanical seal was proposed. The electric eddy current sensor made direct measurement in the internal of mechanical seal device, and the acoustic emission sensor was fixed in the outside for indirect measurement. The acoustic emission signals were de-noised by wavelet threshold de-noising method. The representative energy features were selected by wavelet packet energy spectrum algorithm. It was established that the Radial Basis Function neural network model used for identification of the mechanical seal lift-off position, and the extracted wavelet energy features as its input. It was confirmed accurate and effective that the acoustic emission identification technology through comparing with the data detected by electric eddy current sensor. So using the acoustic emission technology realized the identification of the mechanical seal lift-off position of mechanical main shaft from inside to outside. It is convenient to be used and promotion in industrial field.

In view of the strong background noise involved in vibration signal of tool wear and the difficulty to obtain fault frequencies, this paper proposed a tool wear fault feature extraction method based on morphological filters-singularity value decomposition (SVD) with empirical mode decomposition (EMD). Firstly, an experiment system of the cutting tool wear monitoring was set up and a variety of data coming from vibratory sensor were collected, then, the pulse components from the original signal were inhibited by morphological filters and the signal sequences removed outlier were reconstructed, the attractor track matrix was decomposed using SVD for further noise reduction, and then we got weak signal failure frequency after the de-noise signals were decomposed with EMD. Finally, tool wear was identified by GA-B-spline neural network. B-spline networks were trained using genetic algorithms to search for global optimization. The experimental results shown that the diagnosis approach put forward in this paper could identify tool wear fault patterns effectively in noise background.

In view of the strong background noise involved in vibration signal of tool wear and the difficulty to obtain fault frequencies, so, it is important to de-noise before the further processing. However, the traditional de-noising methods, based on Gaussian noise assumption, lose here because the noise is identified as containing a high non-Gaussian component. Independent component analysis (ICA) was recently developed to deal with the blind source separation problem and it is particularly effective in the separation of non-Gaussian signals. So, this paper proposed a signal-noise-separated method with ICA, then de-noise signals are decomposed with empirical mode decomposition (EMD) and we got the better signals characters. Finally, Tool wear by identified by GA-B-spline neural network. B-spline networks is traditionally trained by using gradient-based methods, this may fall into local minimum during the learning process. Here, it is trained using genetic algorithms to search for global optimization. The experimental results show that the diagnosis approach put forward in this paper can effectively identify tool wear fault patterns in noise background and it has great application potential in health condition monitoring of tool wear.

Monitoring the contact state of seal end faces would help the early warning of the seal failure. In the acoustic emission (AE) detection for mechanical seal, the main difficulty is to reduce the background noise and to classify the dispersed features. To solve these problems and achieve higher detection rates, a new approach based on genetic particle filter with autoregression (AR-GPF) and hypersphere support vector machine (HSSVM) is presented. First, AR model is used to build the dynamic state space (DSS) of the AE signal, and GPF is used for signal filtering. Then, multiple features are extracted, and a classification model based on HSSVM is constructed for state recognition. In this approach, AR-GPF is an excellent time-domain method for noise reduction, and HSSVM has advantage on those dispersed features. Finally experimental data shows that the proposed method can effectively detect the contact state of the seal end faces and has higher accuracy rates than some other existing methods.