Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents.

Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)2PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through 1H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)2PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of 1H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by 31P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (Rs)". Significantly, this class of CSAs based on (alkaloid)2linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.

Evaluating the efficacy of different antibiotics against Neisseria gonorrhoeae: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

BACKGROUND: With the widespread use of antibiotics, antimicrobial resistance in Neisseria gonorrhoeae is worsening. The objective of this study was to evaluate the efficacy changes of seven antibiotics in the treatment of N. gonorrhoeae by using Monte Carlo simulation combined with pharmacokinetics/pharmacodynamics/ (PK/PD). METHODS: The minimum inhibitory concentration (MIC) of antibiotics against clinical isolates from 2013 to 2020 in Nanjing, China, was determined by agar dilution method. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens. RESULTS: All dosage regimens of seven antibiotics achieved PTAs ≥ 90% for MIC ≤ 0.06 µg/ml. But when the MIC was increased to 1 µg/ml, PTAs at each MIC value exceeded 90% only for ceftriaxone 1,000 mg and 2,000 mg, zoliflodacin 2,000 mg and 3,000 mg. Among them, the CFR values of each dosing regimen against N. gonorrhoeae only for ceftriaxone, cefixime and zoliflodacin were ≥ 90% in Nanjing from 2013 to 2020. CONCLUSIONS: Cephalosporins are still the first-line drugs in the treatment of gonorrhea. However, the elevated MIC values of cephalosporins can lead to decline in clinical efficacy of the conventional dose regimens, and increasing the dose of ceftriaxone to 1,000 mg-2,000 mg may improve the efficacy. In addition, zoliflodacin is possible to be a potential therapeutic agent in the future.

Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia.

BACKGROUND: The aim of this study was to analyse the differences in the phenotypes of missing teeth between a pair of brothers with hypohidrotic ectodermal dysplasia (HED) and to investigate the underlying mechanism by comparing the mutated gene loci between the brothers with whole-exome sequencing. METHODS: The clinical data of the patients and their mother were collected, and genomic DNA was extracted from peripheral blood samples. By Whole-exome sequencing filtered for a minor allele frequency (MAF) ≤0.05 non-synonymous single-nucleotide variations and insertions/deletions variations in genes previously associated with tooth agenesis, and variations considered as potentially pathogenic were assessed by SIFT, Polyphen-2, CADD and ACMG. Sanger sequencing was performed to detect gene variations. The secondary and tertiary structures of the mutated proteins were predicted by PsiPred 4.0 and AlphaFold 2. RESULTS: Both brothers were clinically diagnosed with HED, but the younger brother had more teeth than the elder brother. An EDA variation (c.878 T > G) was identified in both brothers. Additionally, compound heterozygous variations of WNT10A (c.511C > T and c.637G > A) were identified in the elder brother. Digenic variations in EDA (c.878 T > G) and WNT10A (c.511C > T and c.637G > A) in the same patient have not been reported previously. The secondary structure of the variant WNT10A protein showed changes in the number and position of α-helices and ß-folds compared to the wild-type protein. The tertiary structure of the WNT10A variant and molecular simulation docking showed that the site and direction where WNT10A binds to FZD5 was changed. CONCLUSIONS: Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.

Efficient Electrosynthesis of Urea over Single-Atom Alloy with Electronic Metal Support Interaction.

Urea electrosynthesis from carbon dioxide (CO2) and nitrate (NO3-) is an alternative approach to traditional energy-intensive urea synthesis technology. Herein, we report a CuAu single-atom alloy (SAA) with electronic metal support interaction (EMSI), achieving a high urea yield rate of 813.6 µg h-1 mgcat-1 at -0.94 V versus reversible hydrogen electrode (vs. RHE) and a Faradaic efficiency (FE) of 45.2% at -0.74 V vs. RHE. In-situ experiments and theoretical calculations demonstrated that single-atom Cu sites modulate the adsorption behavior of intermediate species. Bimetallic sites synergistically accelerate C-N bond formation through spontaneous coupling of *CO and *NO to form *ONCO as key intermediates. More importantly, electronic metal support interaction between CuAu SAA and CeO2 carrier further modulates electron structure and interfacial microenvironment, endowing electrocatalysts with superior activity and durability. This work constructs SAA electrocatalysts with EMSI effect to tailor C-N coupling at the atomic level, which can provide guidance for the development of C-N coupling systems.

Investigation on hybrid laser ablation and its application in fused silica damage mitigation.

We present and investigate a hybrid laser-based method of surface shaping for damage mitigation on fused silica surfaces. Damage sites were removed and precisely shaped into an optically-benign cone by a procedure of femtosecond laser ablation with a subsequent CO2 laser polishing process. The morphology of the cone rim was quantitatively predicted by a numerical model. Since the heat-affected zone (HAZ) of the laser polishing process was effectively confined by the optimization of ablation parameters, the dimensions of the raised rim were reduced by an order of magnitude. The intensity of the on-axis hotspot was positively related to the dimensions of the raised rim, and thus an inapparent downstream intensification was achieved by the rim reduction. Laser-induced damage threshold (LIDT) of the cone was tested to be ∼14 J/cm2 on the input surface. Therefore, the presented method is appropriate to mitigate damage and also provides a promising approach to manufacturing functional microstructures for high-power applications.

Advanced LD pumped 3.3 J/1 Hz nanosecond Nd:glass preamplifier for SG-II upgrade laser facility.

We demonstrate a laser-diode-pumped multipass Nd:glass laser amplifier with a range of advanced characteristics. The amplifier exhibits high extraction efficiency, enables arbitrary shaping of spatial beam intensity, and effectively suppresses frequency modulation to amplitude modulation conversion. Our approach achieves excellent beam quality via thermal lensing and thermal depolarization compensation. When a 1.82 mJ/5 ns laser pulse was injected into the amplifier, the output energy reached up to 3.3 J with a repetition rate of 1 Hz at a central wavelength of 1053.3 nm. The near-field modulation of the amplified output beam was below 1.2, and the far-field focusing ability of the beam was 90% at 2.9 times the diffraction limit. This laser amplifier system holds potential for integration as a preamplifier within the SG-II upgrade high power laser facility.

Synthesis of AuX (X = Ni, Ga, Mo, Zn, and Cr) Alloy Aerogels as High-Performance Electrocatalytic CO2 Reduction Reaction Catalysts.

Electrocatalytic CO2 reduction reaction (eCO2RR) into value-added chemicals is highly desirable to mitigate the global warming effect and energy crisis. Metal aerogels, as featured by a self-supporting structure, large specific surface area, outstanding conductivity, and a hierarchical porous structure, are ideal electrocatalysts in eCO2RR. Herein, we report a simple and general strategy for constructing a series of Au-based alloy aerogels which contain Au with another metal including Ga, Ni, Mo, Zn, and Cr, respectively. For the first time, the electrocatalytic activities of AuGa aerogels, AuNi aerogels, and AuMo aerogels for CO2RR were studied in detail. The resultant Au81Ga19 aerogel achieves a 95.2% Faradaic efficiency (FE) at -1.16 V versus reversible hydrogen (vs RHE) in H-cells. Impressively, a total 99.4% FE for C1 products (CO + HCOOH) with a current density of 100 mA cm-2 at -0.6 V vs RHE and a large current density of 228 mA cm-2 can be achieved at -0.9 V with a 72.3% FE for the C1 product in a flow cell. Electrochemical characterization and theoretical calculations further revealed that the outstanding performance of the Au-based aerogels was derived from the large specific surface area, abundant grain boundaries, low interfacial charge transfer resistance, and synergetic effect. Overall, this study provides a promising alternative to engineer alloy aerogel electrocatalysts for highly efficient CO2 electroreduction.

Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3.

BACKGROUND: Beiging of white fat plays an important role in energy metabolism. Beige adipocytes contribute to the regulation of body weight and body temperature through expenditure of chemical energy to produce heat, and they have therefore recently attracted considerable attention as potential targets for therapeutic approaches in metabolic disorders, including obesity. All adipocytes, including beige adipocytes, differentiate from mesenchymal stem cells (MSCs), which may provide an important path for clinical intervention; however, the mechanism of beiging of human adipose cell-derived MSCs is not fully understood. Here, we provide insights on the role of IRISIN, which is known to be secreted by skeletal muscle and promote beiging of white fat. RESULTS: We established an IRISIN-induced mesenchymal stem cell beiging model and found that IRISIN protein interacts with the MSC membrane protein TRPC3. This interaction results in calcium influx and consequential activation of Erk and Akt signaling pathways, which causes phosphorylation of PPARγ. The phosphorylated PPARγ enters the nucleus and binds the UCP1 promoter region. Furthermore, the role of TRPC3 in the beiging of MSCs was largely abolished in Trpc3-/- mice. We additionally demonstrate that the calcium concentration in the brain of mice increases upon IRISIN stimulation, followed by an increase in the content of excitatory amino acids and norepinephrine, while Trpc3-/- mice exhibit the reverse effect. CONCLUSIONS: We found that TRPC3 is a key factor in irisin-induced beiging of MSCs, which may provide a new target pathway in addressing metabolic disorders. Our results additionally suggest that the interaction of irisin with TRPC3 may affect multiple tissues, including the brain.

Relationships among social support, coping style, self-stigma, and quality of life in patients with diabetic foot ulcer: A multicentre, cross-sectional study.

Patients with diabetic foot ulcer have a significantly lower quality of life. Quality of life could be connected to other psychological or social processes. The purpose of this study was to examine the relationships between social support, decision regret, self-stigma, and quality of life in patients with diabetic foot ulcers. The sample of the study consisted of 229 diabetic foot ulcer patients. Data were collected from September 2019 to March 2020. The demographic and clinical information, the Stigma Scale for Chronic Illness, Medical Coping Scale, Social Support Scale, and Quality of Life scale were used to assess the quality life for diabetic foot ulcer. Pearson correlation coefficient and structural equation modelling were used for data analysis. The quality of life was negatively correlated with self-stigma, positively correlated with social support, giving up coping, and not significantly correlated with confrontation coping and avoidance coping. Self-stigma has significant indirect effects on quality of life through social support and coping style. Further clinical intervention strategies for decreasing self-stigma as well as strengthening social support and positive coping styles are needed to inform diabetic foot ulcer patients, thus improving their quality of life.

In Vitro Activity of Ertapenem against Neisseria gonorrhoeae Clinical Isolates with Decreased Susceptibility or Resistance to Extended-Spectrum Cephalosporins in Nanjing, China (2013 to 2019).

Neisseria gonorrhoeae isolates collected in Nanjing, China, that possessed decreased susceptibility (or resistance) to extended-spectrum cephalosporins (ESCs) were examined for susceptibility to ertapenem, and their sequence types were determined. Ceftriaxone and cefixime MICs of ≥0.125 mg/L and ≥0.25 mg/L, respectively, were first determined in 259 strains isolated between 2013 and 2019, and then MICs of ertapenem were measured using the antimicrobial gradient Epsilometer test (Etest). Also, genetic determinants of ESC resistance were identified and N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed to analyze associations with ertapenem susceptibility. All isolates displayed ertapenem MICs between 0.006 mg/L and 0.38 mg/L; the overall MIC50 and MIC90 were 0.032 mg/L and 0.125 mg/L, respectively. Forty-four (17.0%) isolates displayed ertapenem MICs of ≥0.125 mg/L; 10 (3.9%) had MICs of ≥0.25 mg/L. The proportion of isolates with ertapenem MICs of ≥0.125 mg/L increased from 4.0% in 2013 to 20.0% in 2019 (χ2 = 24.144, P < 0.001; chi-square test for linear trend). The penA mosaic allele was present in a significantly higher proportion of isolates with ertapenem MICs of ≥0.125 mg/L than of isolates with MICs of ≤0.094 mg/L) (97.7% versus 34.9%, respectively; χ2 = 58.158, P < 0.001). ST5308 was the most prevalent NG-MAST type (8.5%); ST5308 was also significantly more common among isolates with ertapenem MICs of ≥0.125 mg/L than isolates with MICs of ≤0.094 mg/L (22.7% and 5.6%, respectively; χ2 = 13.815, P = 0.001). Ertapenem may be effective therapy for gonococcal isolates with decreased susceptibility or resistance to ESCs and isolates with identifiable genetic resistance determinants.

Characterization of the Dual Functions of LvCrustinVII from Litopenaeus vannamei as Antimicrobial Peptide and Opsonin.

Crustin are a family of antimicrobial peptides that play an important role in protecting against pathogens infection in the innate immune system of crustaceans. Previously, we identified several novel types of crustins, including type VI and type VII crustins. However, their immune functions were still unclear. In the present study, the immune function of type VII crustin LvCrustinVII were investigated in Litopenaeus vannamei. LvCrustinVII was wildly expressed in all tested tissues, with relatively high expression levels in hepatopancreas, epidermis and lymphoid organ. Upon Vibrio parahaemolyticus infection, LvCrustinVII was significantly upregulated in hepatopancreas. Recombinant LvCrustinVII (rLvCrustinVII) showed strong inhibitory activities against Gram-negative bacteria Vibrio harveyi and V. parahaemolyticus, while weak activities against the Gram-positive bacteria Staphylococcus aureus. Binding assay showed that rLvCrustinVII could bind strongly to V. harveyi and V. parahaemolyticus, as well as the cell wall components Glu, LPS and PGN. In the presence of Ca2+, rLvCrustinVII could agglutinate V. parahaemolyticus and enhance hemocyte phagocytosis. The present data partially illustrate the immune function of LvCrustinVII, which enrich our understanding on the functional mechanisms of crustins and provide useful information for application of this kind of antimicrobial peptides.

In vitro and in vivo study on angiogenesis of porcine induced pluripotent stem cell-derived endothelial cells.

Pluripotent stem cells (PSCs) are a promising source of endothelial cells (ECs) for the treatment of cardiovascular diseases. Since clinical application of embryo stem cells (ESCs) involves issues of medical ethics and risk of immune rejection, induced pluripotent stem cells (iPSCs) will facilitate cell transplantation therapy for the cardiovascular diseases. Swine is identified as an ideal large-animal model for human, because of its similar organ size and physiological characteristics. However, there are very few studies on EC differentiation of porcine iPSCs (piPSCs). In recent study, we provided an efficient protocol to differentiate piPSCs into ECs with the purity of 19.76% CD31 positive cells within 16 days. Passaging of these cells yielded a nearly pure population, which also expressed other endothelial markers such as CD144, eNOS and vWF. Besides, these cells exhibited functions of ECs such as uptake of low-density lipoprotein and formation of tubes in vitro or blood vessels in vivo. Our study successfully obtained ECs from piPSCs via a feeder- and serum-free monolayer system and demonstrated their angiogenic function in vivo and in vitro. piPSC-ECs derivation is not only potential for the autologous cell transplantation and cardiovascular drug screening, but also for the mechanistic studies on EC differentiation and endothelial dysfunction.

Derivation and Characterization of Endothelial Cells from Porcine Induced Pluripotent Stem Cells.

Although the study on the regulatory mechanism of endothelial differentiation from the perspective of development provides references for endothelial cell (EC) derivation from pluripotent stem cells, incomplete reprogramming and donor-specific epigenetic memory are still thought to be the obstacles of iPSCs for clinical application. Thus, it is necessary to establish a stable iPSC-EC induction system and investigate the regulatory mechanism of endothelial differentiation. Based on a single-layer culture system, we successfully obtained ECs from porcine iPSCs (piPSCs). In vitro, the derived piPSC-ECs formed microvessel-like structures along 3D gelatin scaffolds. Under pathological conditions, the piPSC-ECs functioned on hindlimb ischemia repair by promoting blood vessel formation. To elucidate the molecular events essential for endothelial differentiation in our model, genome-wide transcriptional profile analysis was conducted, and we found that during piPSC-EC derivation, the synthesis and secretion level of TGF-ß as well as the phosphorylation level of Smad2/3 changed dynamically. TGF-ß-Smad2/3 signaling activation promoted mesoderm formation and prevented endothelial differentiation. Understanding the regulatory mechanism of iPSC-EC derivation not only paves the way for further optimization, but also provides reference for establishing a cardiovascular drug screening platform and revealing the molecular mechanism of endothelial dysfunction.

Spiritual care needs and their associated influencing factors among elderly patients with moderate-to-severe chronic heart failure in China: A cross-sectional study.

BACKGROUND: The significance of spiritual care needs among chronic diseases patients has been emphasized across countries and cultures in many studies. However, there were few studies on spiritual care needs among elderly patients with moderate-to-severe chronic heart failure (CHF) in China. OBJECTIVE: To investigate spiritual care needs and associated influencing factors among elderly patients with moderate-to-severe CHF, and to examine the relationships among spiritual care needs, self-perceived burden, symptom management self-efficacy, and perceived social support. METHODS: A cross-sectional design was implemented, and the STROBE Checklist was used to report the study. A convenience sample of 474 elderly patients with moderate-to-severe CHF were selected from seven hospitals in Tianjin, China. The sociodemographic characteristics questionnaire, the Spiritual Needs Questionnaire Scale, the Self-Perceived Burden Scale, the Self-efficacy for Symptom Management Scale, and the Perceived Social Support Scale were used. Descriptive statistics, univariate, multiple linear regression, and Pearson's correlation analysis were used to analyze data. RESULTS: The total score of spiritual care needs among 474 elderly patients with moderate-to-severe CHF was 37.95 ± 14.71, which was moderate. Religious belief, educational background, self-perceived burden, symptom management self-efficacy, and perceived social support were the main factors affecting spiritual care needs, and spiritual care needs were negatively correlated with self-perceived burden (r = -0.637, p < 0.01) and positively correlated with symptom management self-efficacy (r = 0.802, p < 0.01) and social support (r = 0.717, p < 0.01). SIGNIFICANCE OF RESULTS: The spiritual care needs of elderly patients with moderate-to-severe CHF were moderate, which were influenced by five factors. It is suggested that clinical nurses, families, and society should take targeted spiritual care measures to improve patients' symptom management self-efficacy and perceived social support from many aspects, and reduce self-perceived burden to meet their spiritual care needs and improve the quality and satisfaction of spiritual care in nursing practice.

Needs for nurses to provide spiritual care and their associated influencing factors among elderly inpatients with stroke in China: A cross-sectional quantitative study.

OBJECTIVES: To investigate the spiritual care needs and associated influencing factors among elderly inpatients with stroke, and to examine the correlations among spiritual care needs, spiritual well-being, self-perceived burden, self-transcendence, and social support. METHODS: A cross-sectional quantitative design was implemented, and the STROBE Checklist was used as the foundation of the study. A convenience sample of 458 elderly inpatients with stroke was selected from three hospitals in China. The sociodemographic characteristics questionnaire, the Nurse Spiritual Therapeutics Scale, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being, the Self-Perceived Burden Scale, the Chinese Self-Transcendence Scale, and the Perceived Social Support Scale were used. Descriptive statistics, correlation, Student's t-test, ANOVA, non-parametric, and multiple linear regression analyses were used to analyze the data. RESULTS: The total score of spiritual care needs was 29.82 ± 7.65. Spiritual care needs were positively correlated with spiritual well-being (r = 0.709, p < 0.01), self-transcendence (r = 0.710, p < 0.01), and social support (r = 0.691, p < 0.01), whereas being negatively correlated with self-perceived burden (r = -0.587, p < 0.01). Religious beliefs, educational level, residence place, disease course, spiritual well-being, self-perceived burden, self-transcendence, and social support were found to be the main influencing factors. SIGNIFICANCE OF RESULTS: The spiritual care needs were prevalent and moderate. It is suggested that nurses should enhance spiritual care knowledge and competence, take targeted spiritual care measures according to inpatients' individual personality traits or characteristics and differences of patients, reduce their self-perceived burden and improve their spiritual well-being, self-transcendence and social support in multiple ways and levels, so as to meet their spiritual care needs to the greatest extent and enhance their spiritual comfort.

Correlations among spiritual care competence, spiritual care perceptions and spiritual health of Chinese nurses: A cross-sectional correlational study.

BACKGROUND: The significance of spiritual care competence among nurses has been emphasized across countries and cultures in many studies. However, there were few studies on correlations among spiritual care competence, spiritual care perceptions, and spiritual health of nurses in China. OBJECTIVE: To investigate spiritual care competence, spiritual care perceptions, and spiritual health, and examine the correlations among spiritual care competence, spiritual care perceptions and spiritual health, and the mediating role of spiritual health between other two variables of Chinese nurses. METHODS: A cross-sectional and correlational design was implemented, and the STROBE Checklist was used to report the study. A convenience sample of 2,181 nurses were selected from 17 hospitals in 3 provinces, China. Participants provided data on sociodemographic by completing the Chinese Version of the Spiritual Care Competence Scale, the Chinese Version of the Spiritual Care-Giving Scale, and the Spiritual Health Scale Short Form. Descriptive statistics, univariate, multiple linear regression, and Pearson correlation analysis were used to analyze data. RESULTS: The total scores of spiritual care competence, spiritual care perceptions, and spiritual health were 58.25 ± 16.21, 144.49 ± 16.87, and 84.88 ± 10.57, respectively, which both were moderate. Spiritual care competence was positively correlated with spiritual care perceptions (r = 0.653, p < 0.01) and spiritual health (r = 0.587, p < 0.01). And spiritual health played a mediating role between the other two variables (accounting for 35.6%). SIGNIFICANCE OF RESULTS: The spiritual care competence, spiritual care perceptions, and spiritual health of Chinese nurses need to be improved. It is recommended that nursing managers should pay attention to spiritual care education of nurses, and improve spiritual care perceptions and spiritual health in multiple ways, so as to improve their spiritual care competence and to maximize the satisfy spiritual care needs of patients in China.

Susceptibility Trends of Zoliflodacin against Multidrug-Resistant Neisseria gonorrhoeae Clinical Isolates in Nanjing, China, 2014 to 2018.

Previously, we reported the potent activity of a novel spiropyrimidinetrione, zoliflodacin, against Neisseria gonorrhoeae isolates collected in 2013 from symptomatic men in Nanjing, China. Here, we investigated trends of susceptibilities to zoliflodacin in 986 isolates collected from men between 2014 and 2018. N. gonorrhoeae isolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Mutations in the gyrA, gyrB, parC, parE, and mtrR genes were determined by PCR and sequencing. The MICs of zoliflodacin ranged from ≤0.002 to 0.25 mg/liter; the overall MIC50 and MIC90 were 0.06 mg/liter and 0.125 mg/liter, respectively, in 2018, increasing 2-fold from 2014. However, the percentage of isolates with lower zoliflodacin MICs declined in each year sequentially, while the percentage with higher MICs increased yearly (P ≤ 0.00001). All isolates were susceptible to spectinomycin but resistant to ciprofloxacin (MIC ≥ 1 mg/liter); 21.2% (209/986) were resistant to azithromycin (≥1 mg/liter), 43.4% (428/986) were penicillinase-producing N. gonorrhoeae (PPNG), 26.9% (265/986) were tetracycline-resistant N. gonorrhoeae (TRNG), and 19.4% (191/986) were multidrug-resistant (MDR) isolates. 202 isolates with the lowest (≤0.002 to 0.015 mg/liter) and highest (0.125 to 0.25 mg/liter) zoliflodacin MICs were quinolone resistant with double or triple mutations in gyrA; 193/202 (95.5%) also had mutations in parC There were no D429N/A and/or K450T mutations in GyrB identified in the 143 isolates with higher zoliflodacin MICs; an S467N mutation in GyrB was identified in one isolate. We report that zoliflodacin continues to have excellent in vitro activity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin, and extended-spectrum cephalosporins.

High-contrast OPCPA front end in high-power petawatt laser facility based on the ps-OPCPA seed system.

A high-energy, high-beam-quality, high-contrast picosecond optical parametric chirped-pulse amplification (ps-OPCPA) laser system was demonstrated. The pulse from a femtosecond oscillator was stretched to 4 ps, after which it was amplified from 140 pJ to 600 µJ by an 8 ps/6 mJ pump laser in two non-collinear OPCPA stages. The total gain was >106, and the root mean square of the energy stability of the laser system was 1.6% in 10 h. The contrasts of the solid and fiber mode-locked femtosecond oscillator-seeded ps-OPCPA systems were compared, and a signal-to-noise ratio of >1011 was achieved. Using this system, the contrast of the front end in high-power picosecond petawatt laser facility was improved by ∼40 dB to >1011, beyond ∼200 ps ahead of the main pulse with an output level of 60 mJ.

High-stability, high-energy Nd:glass rod regenerative amplifier with compensation for cavity misalignment.

We report on an Nd:glass large-mode rod regenerative amplifier with a pulse energy of 125 mJ at 1053 nm. The amplifier contains a linear-type resonator, which is designed in Stability Zone II with a misalignment sensitivity factor of 12.9 m. A method is proposed for analyzing the sensitivity of the mode displacement on the gain media to cavity misalignment, and the optimum solution to compensation for cavity misalignment is obtained and applied to the amplifier. The amplifier exhibits excellent energy stability with a fluctuation of 0.47% (RMS) within 7 h and high spatial beam quality with M2=1.17. The beam pointing stability in the horizontal and vertical axes within 7 h is 2.7 and 3.6 µrad (RMS), respectively.

Interspecies cell fusion between mouse embryonic stem cell and porcine pluripotent cell.

In the area of stem cell research, fusion of somatic cells into pluripotent cells such as mouse embryonic stem (ES) cells induces reprogramming of the somatic nucleus and can be used to study the effect of trans-acting factors from the pluripotent cell on the pluripotent state of somatic nucleus. As many other groups, we previously established a porcine pluripotent cell line at a low potential. Therefore, here, we performed experiments to investigate if the fusion with mouse ES cell could improve the pluripotent state of porcine pluripotent cell. Our data showed that resultant mouse-porcine interspecies fused cells are AP positive, and could be passaged up to 20 passages. Different degrees of increases in expression of porcine pluripotent genes proved that pig-origin gene network can be programmed by mouse ES. Further differentiation study also confirmed these fused cells' potential to form three germ layers. However, unexpectedly, we found that chromosome loss and aberrant (especially in porcine chromosomes) is severe after the cell fusion, implying that interspecies cell fusion may be not suitable to study porcine pluripotency without additional supportive conditions for genome stabilization.