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We demonstrate, to the best of our knowledge, the first double-pass pre-chirp managed fiber amplifier. The double-pass fiber amplifier exhibits high gain allowing us to amplify chirped picosecond pulses from 20 mW to 113 W in a rod-type Yb-fiber corresponding to 38 dB gain. We study the dependence of static mode degradation (SMD) on the nonlinear phase shift (NPS) accumulated by the amplified pulse. Our results indicate that a larger nonlinear phase shift results in stronger nonlinear polarization evolution of the fundamental mode and leads to a lower threshold for SMD. After optimization, our pre-chirp managed amplifier seeded by 80 mW pulses delivers 102 W amplified power from the main output. The amplified pulses are compressed to 37 (55) fs with 90 (100) W average power by a grating pair (chirped mirrors). The double-pass configuration significantly simplifies the implementation of pre-chirp managed fiber amplifiers leading to an extremely compact system.

Gut microbiota have been targeted by alternative therapies for non-communicable diseases. We examined the gut microbiota of a healthy Taiwanese population, identified various bacterial drivers in different demographics, and compared them with dialysis patients to associate kidney disease progression with changes in gut microbiota.This was a cross-sectional cohort study.Fecal samples were obtained from 119 healthy Taiwanese volunteers, and 16S rRNA sequencing was done on the V3-V4 regions to identify the bacterial enterotypes. Twenty-six samples from the above cohort were compared with fecal samples from 22 peritoneal dialysis and 16 hemodialysis patients to identify species-level bacterial biomarkers in the dysbiotic gut of chronic kidney disease (CKD) patients.Specific bacterial species were identified pertaining to different demographics such as gender, age, BMI, physical activity, and sleeping habits. Dialysis patients had a significant difference in gut microbiome composition compared to healthy controls. The most abundant genus identified in CKD patients wasThis study characterizes the healthy gut microbiome of a Taiwanese population in terms of various demographics. In a case-control examination, the results showed the alteration in gut microbiota in CKD patients corresponding to different dialysis treatments. Also, this study identified the bacterial species abundant in CKD patients and their possible role in complicating the patients' condition.

Cognitive and noncognitive skills are critical for a host of economic and social outcomes as an adult. While there is broad agreement that a significant amount of skill acquisition and development occurs early in life, the precise activities and investments that drive this process are not well understood. In this paper we examine how children’s time allocation affects their accumulation of skill. Children’s time allocation is endogenous in a model of skill production since it is chosen by parents and children. We apply a recently developed test of exogeneity to search for models that yield causal estimates of the impact time inputs have on child skills. We show that the test, which exploits bunching in time inputs induced by a non-negativity time constraint, has power to detect endogeneity stemming from omitted variables, simultaneity, measurement error, and several forms of model misspecification. We find that with a sufficiently rich set of controls, we are unable to reject exogeneity in our most detailed production function specifications. The estimates from these models indicate that active time with adult family members, such as parents and grandparents, are the most productive in generating cognitive skill.

Olfactory dysfunction is related to several clinical neurodegenerative diseases, such as Alzheimer’s disease, multiple sclerosis, degenerative ataxias, Parkinson’s disease, and so on. Owing to the individual difference in the sensory adaption of human smell function, the olfactory responses usually exhibit large inter-individual difference and change over time after repeated stimulations. The traditional analysis tools, such as statistical parametric mapping (SPM) in functional magnetic resonance imaging technique (fMRI) analysis, utilize the paradigm-based linear correlation and statistical techniques to discriminate the activation areas from background activities. However, these traditional approaches extract olfactory-induced responses using the stereotypic template or paradigm generated model. The olfactory-induced hemodynamic responses affected by internal/external events, such as changes of smell fatigue and attention, are not considered and therefore could result in misleading results. In this paper, owing to the stochastic characteristic of olfactory-induced responses, we adopted multivariate empirical mode decomposition (MEMD) to extract olfactory-induced hemodynamic responses in MRI blood-oxygen-level dependent (BOLD) signals. The MEMD is an efficient data-driven approach to extract nonlinear and non-stationary signals, which is an improved method to expand traditional empirical mode decomposition (EMD) from one channel to multi-channel processing. We applied MEMD to decompose time series of BOLD signals from each slice into multivariate intrinsic mode functions (IMF). The MEMD enables common features of different scales in an image slice to be arranged in distinct IMFs. Each IMF is an analytic, self-constructed, well-defined, and data-driven function with time-varying frequencies. Each IMF was examined by checking its correlation with the paradigm-generated template. The task-related IMFs were chosen to reconstruct olfactory-induced hemodynamic responses. The group analysis of MEMD-processed data showed olfactory-induced activations in the anterior cingulate cortex and middle frontal gyrus.

Olfactory dysfunction is related to several clinical neurodegenerative diseases, such as Alzheimer's disease, multiple sclerosis, degenerative ataxias, Parkinson's disease, and so on. Owing to the individual difference in the sensory adaption of human smell function, the olfactory responses usually exhibit large inter-individual difference and change over time after repeated stimulations. The traditional analysis tools, such as statistical parametric mapping (SPM) in functional magnetic resonance imaging technique (fMRI) analysis, utilize the paradigm-based linear correlation and statistical techniques to discriminate the activation areas from background activities. However, these traditional approaches extract olfactory-induced responses using the stereotypic template or paradigm generated model. The olfactory-induced hemodynamic responses affected by internal/external events, such as changes of smell fatigue and attention, are not considered and therefore could result in misleading results. In this paper, owing to the stochastic characteristic of olfactory-induced responses, we adopted multivariate empirical mode decomposition (MEMD) to extract olfactory-induced hemodynamic responses in MRI blood-oxygen-level dependent (BOLD) signals. The MEMD is an efficient data-driven approach to extract nonlinear and non-stationary signals, which is an improved method to expand traditional empirical mode decomposition (EMD) from one channel to multi-channel processing. We applied MEMD to decompose time series of BOLD signals from each slice into multivariate intrinsic mode functions (IMF). The MEMD enables common features of different scales in an image slice to be arranged in distinct IMFs. Each IMF is an analytic, self-constructed, well-defined, and data-driven function with time-varying frequencies. Each IMF was examined by checking its correlation with the paradigm-generated template. The task-related IMFs were chosen to reconstruct olfactory-induced hemodynamic responses. The group analysis of MEMD-processed data showed olfactory-induced activations in the anterior cingulate cortex and middle frontal gyrus.

High harmonic generation (HHG) delivering attosecond pulse duration with photon energy in the extreme ultraviolet spectral range has been demonstrated as a robust table-top coherent light source, allowing for the observation and manipulation of ultrafast process within the shortest time window ever made by humans. The past decade has witnessed the rapid progress of HHG from a variety of solid targets and its application for photoemission spectroscopy in condensed matter. In this article, we review the HHG in solids and the understanding of the underlying physics of HHG, which allows all-optical band structure reconstruction. We also introduce combinations of HHG source and photoemission spectroscopy, such as angular-resolved photoemission spectroscopy and photoemission electron microscopy. With the capacity of exploring a wide momentum space and high temporal resolution, the extension of attosecond science to the field of condensed matter physics will lead to new insights into the fundamental ultrafast dynamics in novel quantum materials.

Escherichia coli is one major cause of bacterial infections and can horizontally acquire antimicrobial resistance and virulence genes through conjugation. Because conjugative plasmids can rapidly spread among bacteria of different species, the plasmids carrying both antimicrobial resistance and virulence genes may pose a significant threat to public health. Therefore, the identification and characterization of these plasmids may facilitate a better understanding of E. coli pathogenesis and the development of new strategies against E. coli infections. Because iron uptake ability is a potential virulence trait of bacteria, we screened for E. coli conjugative plasmids able to confer both iron uptake ability and ampicillin resistance. The plasmid pEC41, which was derived from the bacteremia clinical isolate EC41, was identified. EC41, which carried the fimH27 allele, belonged to sequence type (ST) 405 and phylogroup D. According to the sequencing analyses, pEC41 was 86 kb in size, and its backbone structure was almost identical to that of another highly conjugative plasmid, pCTX-M3, in which the extended-spectrum β-lactamase gene blaCTX–M–3 was originally identified. pEC41 carried blaCTX–M–3 and blaTEM–1. The ferric citrate uptake (fec) system was identified in pEC41 and was responsible for conferring iron uptake ability. The fec system contributes to the pathogenesis of EC41 in systemic infections but not in urinary tract infections (UTIs). However, this system promoted competitive fitness of a cystitis-associated clinical isolate to colonize urinary tracts. Additionally, the distribution of the fec system was related to E. coli isolates associated with human bacteremia and UTIs. In summary, the present study identified a novel conjugative plasmid, pEC41, which conferred both antimicrobial resistance and an extra iron uptake ability to E. coli. The iron uptake ability was encoded in the fec system and contributed to E. coli pathogenesis. This study is the first to show that the fec system is a virulence factor in E. coli.

The device of multi-pass-cell (MPC) could broaden the spectra of ultrafast laser pulses based on the self-phase-modulation (SPM) effect, which is composed of two concave mirrors and nonlinear mediums. In this paper, the pulse duration of 172 fs is compressed from a 11.3 ps Nd: YVO4 regenerative amplifier at the repetition rate of 1 kHz by using two stages of MPC systems. The pulse duration is shortened by a factor of 66, and the pulse energy of 117 μJ is obtained with a total efficiency of 51%. With high average power Nd-doped laser systems at 10 ps level, this method has the potential to generate high power femtosecond lasers with high efficiency, compact configuration, and low cost.

Escherichia coli is the most common cause of urinary tract infections (UTIs). It is widely accepted that uropathogenic E. coli (UPEC) mainly emerge from the distal gut microbiota. Identification of bacterial characteristics that are able to differentiate UPEC from fecal commensal strains will facilitate the development of novel strategies to detect and monitor the spread of UPEC.Fifty fecal commensal, 83 UTI-associated and 40 biliary tract infection (BTI)-associated E. coli isolates were analyzed. The NotI restriction patterns of chromosomal DNA in the isolates were determined by pulse-field gel electrophoresis. The phylogenetic types and the presence of 9 known virulence genes of each isolate were determined by PCR analyses. Additionally, the susceptibilities of the isolates to antibiotics were revealed. Then the associations of NotI resistance with UTI-associated isolates, phylotypes, and antibiotic resistance were assessed.NotI resistance was correlated with UTI-associated isolates, compared to the fecal isolates. Consistently, NotI-resistant isolates harbored a greater number of virulence factors and mainly belonged to phylotype B2. Additionally NotI resistance was correlated with chloramphenicol resistance among the bacteria. Among the fecal, UTI-associated and BTI-associated groups, the distribution of NotI-resistant group B2 isolates was correlated with UTI-associated bacteria.NotI resistance alone is a potential marker for distinguishing fecal strains and UPEC, while the combination of NotI resistance and B2 phylogeny is a candidate marker to differentiate UPEC from fecal and other extraintestinal pathogenic E. coli. Additionally, NotI resistance may be valuable for assessing the potential of chloramphenicol resistance of E. coli.

PurposeDual-specificity protein phosphatases 26 (DUSP26) is a recently identified phosphatase enzyme that regulates MAPK and Akt signaling pathways. The role of DUSP26 in the development and prognosis of high-grade gliomas (HGGs) and primary glioblastoma (GBM) has remained unclear and was the focus of this study.Materials and MethodsThe prognostic value of DUSP26 was assessed using retrospective analyses using online data sets and tissue microarray of HGGs. U251 and U87 cells modified to overexpress DUSP26 were utilized to study the role of DUSP26 in cell growth, migration, and cell apoptosis analyzed by CCK-8 assay, clonogenic, transwell migration, and TUNEL, respectively. The phosphorylation of proteins in MAPK and Akt signaling pathways was assayed by Western blot and immunofluorescence assays.ResultsAnalyses using available online data sets and tissue microarray showed that DUSP26 is down-regulated in high-grade gliomas and GBM as compared to normal brain. Stratification of glioma patients based on DUSP26 expression level showed an inverse correlation between DUSP26 expression and patient survival. At the cellular level, DUSP26 overexpression led to decreased cell proliferation, migration, and senescence in U251 and U87 cells, whereas apoptosis was increased as compared to corresponding controls. Interestingly, the biologic effects of DUSP26 overexpression were associated with the dephosphorylation of proteins in the MAPK and Akt signaling pathways.ConclusionsThese findings suggest that the loss of DUSP26 expression, seen in a subset of high-grade gliomas and GBM patients, facilitates malignant behavior; and with inverse correlation between its expression levels with patient survival. DUSP26 can serve as an independent prognostic factor.

In this study we propose a construction framework utilizing stepwise integrations and the Sherman-Morrison-Woodbury formula to seek pseudospectral integration preconditioning matrices for differential operators. We illustrate this framework through formulating an inverse matrix for the Helmholtz differential operator of the form $\frac{d}{dx} a(x) \frac{d}{dx} + c(x)$. Numerical experiments were conducted to examine the performance of the derived operator. The results show that the inverse matrix is an effective solution operator to numerically solve general second order differential equations.

Background Flagella‐mediated motility is both a crucial virulence determinant of Helicobacter pylori and a factor associated with gastrointestinal diseases. Flagellar formation requires flagellins to be glycosylated with pseudaminic acid (Pse), a process that has been extensively studied. However, the transfer of Pse to flagellins remains poorly understood. Therefore, the aim of this study is to characterize a putative glycosyltransferase jhp0106 in flagellar formation. Materials and Methods Western blotting and chemical deglycosylation were performed to examine FlaA glycosylation. Protein structural analyses were executed to identify the active site residues of Jhp0106, while the Jhp0106‐FlaA interaction was examined using a bacterial two‐hybrid assay. Lastly, site‐directed mutants with mutated active site residues in the jhp0106 gene were generated and investigated using a motility assay, Western blotting, cDNA‐qPCR analysis, and electron microscopic examination. Results Loss of flagellar formation in the Δjhp0106 mutant was confirmed to be associated with non‐glycosylated FlaA. Furthermore, three active site residues of Jhp0106 (S350, F376, and E415) were identified within a potential substrate‐binding region. The interaction between FlaA and Jhp0106, Jhp0106::S350A, Jhp0106::F376A, or Jhp0106::E415A was determined to be significant. As well, the substitution of S350A, F376A, or E415A in the site‐directed Δjhp0106 mutants resulted in impaired motility, deficient FlaA glycosylation, and lacking flagella. However, these phenotypic changes were regardless of flaA expression, implying an indefinite proteolytic degradation of FlaA occurred. Conclusions This study demonstrated that Jhp0106 (PseE) binds to FlaA mediating FlaA glycosylation and flagellar formation. Our discovery of PseE has revealed a new glycosyltransferase family responsible for flagellin glycosylation in pathogens.

Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host with the capacity for high-throughput analysis. Then, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the simple pathogenicity assay. From the screening, several virulence factors (VFs) involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. The results demonstrated, the simple assay with C. elegans was useful as a UPEC infectious model. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.

The recent years have witnessed the rapid economic growth of our country. The medical industry has also come to a new era. The number of hospital staff continues to increase, while some problems of managing human resource have gradually emerged. These problems have a bad impact on the functions of the hospital. We must attach great importance to solve them. In the process of managing the human resources of hospital, we must insist to put people first. That is how we can better boost the working initiative of medical staff, setting the foundation for the development of hospital in a long run. This article has conducted deepening research on this issue. First of all, it briefly introduced the theory of putting people first. And then it stated the connotation of the theory of putting people first applied in managing human resources of hospital. At last, it explored the strategies on applying the theory of putting people first in managing human resources of hospital in accordance to the concrete conditions.

Background: Traumatic brain injury (TBI) is a brain function change caused by external forces, which is one of the main causes of death and disability worldwide. The aim of this study was to identify early diagnostic markers and potential therapeutic targets for TBI.Methods: Differences between TBI and controls in GSE89866 and GSE104687 were analyzed. The two groups of differentially expressed genes (DEGs) were combined for coexpression analysis, and the modules of interest were performed using enrichment analysis. Hub genes were identified by calculating area under curve (AUC) values of module genes, PPI network analysis, and functional similarity. Finally, the difference in immune cell infiltration between TBI and control was calculated by ssGSEA.Results: A total of 4,817 DEGs were identified in GSE89866 and 1,329 DEGs in GSE104687. They were clustered into nine modules. The genes of modules 1, 4, and 7 had the most crosstalk and were identified as important modules. Enrichment analysis revealed that they were mainly associated with neurodevelopment and immune inflammation. In the PPI network constructed by genes with top 50 AUC values in module genes, we identified the top 10 genes with the greatest connectivity. Among them, down-regulated RPL27, RPS4X, RPL23A, RPS15A, and RPL7A had similar functions and were identified as hub genes. In addition, DC and Tem were significantly up-regulated and down-regulated between TBI and control, respectively.Conclusion: We found that hub genes may have a diagnostic role for TBI. Molecular dysregulation mechanisms of TBI are associated with neurological and immune inflammation. These results may provide new ideas for the diagnosis and treatment of TBI.

Uropathogenic Escherichia coli (UPEC) is the most common pathogen of urinary tract infections (UTIs). Antibiotic therapy is the conventional measure to manage such infections. However, the rapid emergence of antibiotic resistance has reduced the efficacy of antibiotic treatment. Given that the bacterial factors required for the full virulence of the pathogens are potential therapeutic targets, identifying such factors may facilitate the development of novel therapeutic strategies against UPEC UTIs. The peptidoglycan (PG) endopeptidase Spr (also named MepS) is required for PG biogenesis in E. coli. In the present study, we found that Spr deficiency attenuated the ability of UPEC to infect kidneys and induced a fitness defect during bladder colonization in a mouse model of UTI. Based on the liquid chromatography (LC)/mass spectrometry (MS)/MS analysis of the bacterial envelope, spr deletion changed the levels of some envelope-associated proteins, suggesting that Spr deficiency interfere with the components of the bacterial structure. Among the proteins, FliC was significantly downregulated in the spr mutant, which is resulted in reduced motility. Lack of Spr might hinder the function of the flagellar transcriptional factor FlhDC to decrease FliC expression. The motility downregulation contributed to the reduced fitness in urinary tract colonization. Additionally, spr deletion compromised the ability of UPEC to evade complement-mediated attack and to resist intracellular killing of phagocytes, consequently decreasing UPEC bloodstream survival. Spr deficiency also interfered with the UPEC morphological switch from bacillary to filamentous shapes during UTI. It is known that bacterial filamentation protects UPEC from phagocytosis by phagocytes. In conclusion, Spr deficiency was shown to compromise multiple virulence properties of UPEC, leading to attenuation of the pathogen in urinary tract colonization and bloodstream survival. These findings indicate that Spr is a potential antimicrobial target for further studies attempting to develop novel strategies in managing UPEC UTIs.

Background Juvenile xanthogranuloma (JXG) is a type of non-Langerhans cell histiocytosis (non-LCH) that primarily affects infants and young children. It mostly occurs in the skin, while the brain is rarely affected. Multiple intracranial lesions, as found in this case, are even more scarce. Case We are reporting the case of a 9-year-old boy who presented with an imbalanced gait, ataxia, nystagmus, and right facial droop. Magnetic resonance imaging (MRI) revealed multiple intracranial lesions, while chest contrast-enhanced computed tomography (CT) showed irregular soft tissue density of the lesion, with uneven density, poorly defined border, and mild heterogeneous enhancement. Histopathologic examination of the resected intracranial lesion reported disseminated JXG. Subsequently, the patient received treatment of methylprednisolone and interferon-α. The three-month follow-up CT showed that the lesion within the chest was slightly reduced. Conclusion This case report aims to highlight the radiological features, diagnosis, and treatment of intracranial JXG and to provide some guidance for clinical management. Given the rarity of such cases and the lack of relevant studies, further research regarding to diagnosis and treatment is needed.

Isolated attosecond pulse generation in argon is theoretically investigated for different gas pressures and medium lengths. The output of attosecond pulse is effectively enhanced by using a longer gas medium with optimized pressure. The peak intensity of the attosecond pulse by using 6 mm gas medium is doubled compared with that of 1–3 mm gas cell, which is usually used in the experiment. Our simulation shows that the distortion of the driving laser waveform and the absorption are the main factors that limit the output of the attosecond pulse for the long gas medium. Optimized generation condition could be found by balancing the medium length and pressure.

Triazolopyridines are an important kind of fused-ring compounds. A HOCl-promoted triazolopyridine formation strategy is reported here for the first time in which hypochlorous acid (HOCl) mildly and efficiently promotes the formation of 1,2,4-triazolo[4,3-a]pyridines NT1-NT6 from various 2-pyridylhydrazones N1-N6. N6, a rhodol-pyridylhydrazone hybrid, was developed into a fluorescent probe for the selective detection of HOCl, and successfully applied to probe endogenous HOCl in living cells and zebrafish in situ and in real time. The present intramolecular cyclization reaction is selective and atom-economical, thereby not only providing an important approach for the convenient synthesis of triazolopyridines, but also offering a general strategy for sensitive, selective and biocompatible detection of endogenous HOCl in complex biosystems.

The adrenal gland responds to heat stress by epinephrine and glucocorticoid release to alleviate the adverse effects. This study investigated the effect of acute heat stress on the protein profile and histone modification in the adrenal gland of layer-type country chickens. A total of 192 30-week-old roosters were subject to acute heat stress. A resistant group and a susceptible group were identified according to body temperature change after heat stress. Adrenal glands were collected for global protein expression and histone modification analysis. The results indicated that fatty acid amide hydrolase and parathymosin were downregulated, whereas somatostatin, steroidogenic acute regulatory protein, hydroxy-δ-5-steroid dehydrogenase, 3 beta- and steroid δ-isomerase 1, and prostaglandin E synthase 3 were upregulated in the resistant group. Histone modification analysis identified 115 histone markers. The tri-methylation state of histone H3 lysine 27 (H3K27me3) was significantly more abundant in the susceptible group and showed positive crosstalk with K36me and K37me in the H3 tails. Roosters in the heat-resistant group exhibited lower hypothalamus–pituitary–adrenal axis activity but higher reactivity to maintain body temperature homeostasis. Alteration of adrenal H3K27me3 level was associated with the endocrine function of adrenal H3K27me3 and may have contributed to the thermotolerance of chickens.

Background: Increasing studies have been demonstrated that circRNAs play vital regulatory roles in the biological behaviors of glioblastoma cells, and increasing circRNAs are found to have the capacity of encoding small peptides, which are involved in the regulatory process.Methods: Western blot and qRT-PCR were conducted to confirm the expression of SRSF7 and circ-PLEKHA5 respectively. RNase R digestion assay and fluorescence in situ hybridization assays were conducted to evaluate the existence and cellular location of circ-PLEKHA5. RIP assay was used to access the relationship between SRSF7 and circ-PLEKHA5. Dual-luciferase assay and FLAG tag assays were performed to test the coding capability of circ-PLEKHA5. Immunofluorescence assay was conducted to evaluate the location of circ-PLEKHA5-622aa. CCK-8, vasculogenic mimicry (VM) formation and transwell assays were used to evaluate the roles of SRSF7, circ-PLEKHA5, circ-PLEKHA5-622aa on proliferation, VM formation, migration and invasion. Nude mice xenograft studys with PAS-CD34 staining were used to clarify the functional roles of SRSF7 and circ-PLEKHA5 on VM formation in vivo.Results: SRSF7 was up-regulated in glioma, and promoted the proliferation, migration, invasion, VM formation and the expression of VM-associated proteins of glioma cells by increasing the expression of circ-PLEKHA5. Circ-PLEKHA5 was mainly localized in cytoplasm and promoted the proliferation, migration, invasion, VM formation and the expression of VM-associated proteins of glioma cells by encoding a novel protein circ-PLEKHA5-622aa. The application of SRSF7 and circ-PLEKHA5 inhibitor significantly suppressed the tumor growth and VM formation in vivo.Conclusions: This study first demonstrated the coding ability of circ-PLEKHA5, and identified the regulatory roles of SRSF7/circ-PLEKHA5/circ-PLEKHA5-622aa pathway in VM formation of glioblastoma cells. Our findings might provide a novel strategy for glioma treatment.

Superconducting nanowire single photon detector response to X-ray photon was demonstrated using a laser-plasma subps X-ray radiation, to the best of our knowledge. The time jitter was measured to be 248.2 ps, which is larger than ordinary visible or NIR SNSPDs and its efficiency is relatively lower, but the results pave the way for a new competitive X-ray detector with ultrahigh count rates, ultralow timing jitter, ultrahigh sensitivity and negligible dark counts.

Background Extraintestinal pathogenic E. coli (ExPEC) is a common gram-negative organism causing various infections, including urinary tract infections (UTIs), bacteremia, and neonatal meningitis. The cjrABC-senB gene cluster of E. coli contributes to ExPEC virulence in the mouse model of UTIs. Consistently, the distribution of cjrABC-senB is epidemiologically associated with human UTIs caused by E. coli. cjrABC-senB, which has previously been proposed to encode an iron uptake system, may facilitate ExPEC survival in the iron availability-restricted urinary tract. Given that the bloodstream is also an iron limited environment to invading bacteria, the pathogenic role of cjrABC-senB in ExPEC bacteremia, however, remains to be investigated. Methods The ability of ExPEC RS218 strains with and without cjrABC-senB to survive in the mouse bloodstream and human serum was evaluated. Subsequently, the role of this gene cluster in the ExPEC interaction with the complement system was evaluated. Finally, the distribution of cjrABC-senB in human clinical E. coli isolates was determined by PCR. The frequency of cjrABC-senB in bacteremia isolates that were not associated with UTIs (non-UTI bacteremia isolates) was compared with that in UTI-associated isolates and fecal isolates. Results Expression of cjrABC-senB attenuated the survival of RS218 in the mouse bloodstream and human serum. The cjrABC-senB-harboring strains triggered enhanced classical- and alternative-complement pathway activation and became more vulnerable to complement-mediated killing in serum. cjrA was identified as the major gene responsible for the attenuated serum survival. Expressing cjrABC-senB and cjrA increased bacterial susceptibility to detergent and induced periplasmic protein leakage, suggesting that the expression of these genes compromises the integrity of the outer membrane of ExPEC. In addition, the frequency of cjrABC-senB in non-UTI bacteremia isolates was significantly lower than that in UTI-associated isolates, while the frequencies in non-UTI bacteremia isolates and fecal isolates showed no significant difference. Consistently, this epidemiological investigation suggests that cjrABC-senB does not contribute to E. coli bacteremia in humans. Conclusion The contribution of cjrABC-senB to the pathogenesis of ExPEC is niche dependent and contradictory because the genes facilitate ExPEC UTIs but hinder bacteremia. The contradictory niche-dependent characteristic may benefit the development of novel strategies against E. coli-caused infections.

Xing Xiao,1,2,* Wei Chen,3,* Zhe-Wei Wei,4,* Wei-Wei Chu,2 Xiao-Fang Lu,3 Bo Li,1,2 Hong Chen,1 Si-Jun Meng,1 Teng-Fei Hao,1 Ji-Tao Wei,1,2 Yu-Long He,1 Chang-Hua Zhang1 1Center of Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 2Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 3Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 4Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-Hua Zhang; Yu-Long He Email zhchangh@mail.sysu.edu.cn; heyulong@mail.sysu.edu.cnBackground: Nab-paclitaxel has been widely used in treating breast cancer and pancreatic patients for its low toxicity and high efficiency. However, its role in gastric cancer (GC) remains ambiguous. The aim of our study was to test the anti-tumor activity of nab-paclitaxel using GC patient-derived organoids.Methods: By using the organoid culture system, we describe the establishment of human gastric cancer organoid lines from surgical samples of three patients with gastric cancer. The consistency of these organoids with original cancer tissues was evaluated by histopathological examination. The characteristics of the cancer organoids were tested using immunofluorescence (IF) staining. Using organoids, the anti-tumor efficiencies of nab-paclitaxel, 5-Fu and epirubicin were compared by CCK8 assay and Annexin V-FITC/PI staining.Results: Three organoids were successfully established and passaged. The morphology of the established GC organoids was consistent with original cancer tissues. The IC50 of nab-paclitaxel was 3.68 μmol/L in hGCO1, 2.41 μmol/L in hGCO2 and 2.91 μmol/L in hGCO3, which was significantly lower than those of 5-FU (72.99 μmol/L in hGCO1, 28.32 μmol/L in hGCO2 and 2.91 μmol/L in hGCO3) and epirubicin (25.85μmol/L in hGCO1, 15.15 μmol/L in hGCO2 and 7.60 μmol/L in hGCO3). When each organoid lines were treated with nab-paclitaxel for increasing period of time, the percentage of the apoptotic cells in each organoid increased accordingly.Conclusion: Nab-paclitaxel showed strong anti-tumor activity and had the potential to become front-line drug for treating GC patients. Gastric cancer organoid may be a good tool to predict in vivo response to drugs.Keywords: nab-paclitaxel, organoid, gastric cancer, anti-tumor

A new approach for the total synthesis of the active stilbene dimer dehydro

Multi-stage and multi-strategy word representation learning (M2WRL) model with sense and sememe in HowNet outperforms most single-stage and single-strategy models in effectiveness and efficiency. However, fixed stages and using order among strategies are decided empirically, which could lead to poor generalizability of those models. Combined with attention strategy and maximum strategy, this paper proposes an adaptive multistage multi-strategy word representation learning (A-M2WRL) model with senses and sememes in HowNet. Compared with our previous M2WRL model, A-M2WRL model is more generalized, reducing human workload. The effectiveness of A-M2WRL model is evaluated on two classical tasks, word similarity and word analogy. Experiment results indicate that our A-M2WRL model overall outperforms other baselines.

In recent years, the risk of flooding disasters caused by climate change has increased, and a new concept of runoff sharing has been proposed in China. It is an operation method based on the area of ​​the catchment from the perspective of water conservancy. However, the basin area is also a spatial unit of human economic activity. Social and economic development and the distribution of runoff responsibilities clearly show a mutual measurement relationship, and the land has a certain social responsibility to handle its own runoff. How can it be distributed fairly and efficiently? The issue of responsibility for runoff sharing has become an important issue for joint initiatives in the field of soil and water. In the case of considering the watershed as a spatial scope, in addition to considering its own hydrological properties, there are also socioeconomic development issues that should be clarified and discussed step by step. Therefore, this study attempts to use the three-stage data envelopment analysis (DEA) method to consider hydrology The concept of interaction with the socio-economic environment takes into account the impact of exogenous factors on the allocation of runoff responsibility, and evaluates the efficiency of runoff responsibility. In view of this, from the standpoint of the government and residents sharing the runoff, this study effectively combines the different types of data of the social, economic, and ecological environments in the catchment areas to carry out a comprehensive assessment, and weighs out the optimal distribution efficiency of the overall river basin. This study is divided into three parts to clarify the distribution of runoff responsibilities, which are divided into: (1) Establishing an assessment framework for the distribution of river basin runoff responsibilities: Based on the analysis of the spatial unit of the catchment area, an attempt is made to integrate different regional development conditions, which can be summarized Appropriate and appropriate distribution methods; (2) Weighing the fairness and efficiency of the distribution of runoff responsibilities in the spatial unit of the watershed: Point out the current runoff responsibility distribution model and characteristics of the catchment area; (3) Attempt to develop the principles for the use of land use planning, Apply the concept of runoff responsibility to land use planning. Based on the results of this study, a more fair way to distribute runoff responsibilities is proposed, and a new perspective on social natural equality from the river basin scale is clarified. The key factors that affect the distribution of runoff responsibilities are clear. Efficiently undertake total runoff and provide policy planning advice. Try to discuss the issue of runoff responsibility allocation from the field of urban planning, provide river basin runoff responsibility with a planning vision, strengthen the spatial thinking of water and soil dialogue, and look forward to providing a new model of river basin governance in extreme climates.

Hyper-parameters in deep learning are sensitive to prediction results. Non-maximum suppression (NMS) is an indispensable method for the object detection pipelines. NMS uses a pre-defined threshold algorithm to suppress the bounding boxes while their overlaps are not significant. We found that the pre-defined threshold is a hyper-parameter determined by empirical knowledge. We propose an adaptive threshold NMS that uses different thresholds to suppress the bounding boxes whose overlaps are not significant. The proposed adaptive threshold NMS algorithm provides improvements on Faster R-CNN with the AP metric on pneumonia dataset. Furthermore, we intend to propose more methods to optimize the hyper-parameters.

Background Extraintestinal pathogenic E. coli (ExPEC) remains one of the most prevalent bacterial pathogens that cause extraintestinal infections, including neonatal meningitis, septicemia, and urinary tract (UT) infections (UTIs). Antibiotic therapy has been the conventional treatment for such infections, but its efficacy has decreased due to the emergence of antibiotic-resistant bacteria. Identification and characterization of bacterial factors that contribute to the severity of infection would facilitate the development of novel therapeutic strategies. The ExPEC periplasmic protease Prc contributes to the pathogen’s ability to evade complement-mediated killing in the serum. Here, we further investigated the role of the Prc protease in ExPEC-induced UTIs and the underlying mechanism. Methods The uropathogenic role of Prc was determined in a mouse model of UTIs. Using global quantitative proteomic analyses, we revealed that the expression of FliC and other outer membrane-associated proteins was altered by Prc deficiency. Comparative transcriptome analyses identified that Prc deficiency affected expression of the flagellar regulon and genes that are regulated by five extracytoplasmic signaling systems. Results A mutant ExPEC with a prc deletion was attenuated in bladder and kidney colonization. Global quantitative proteomic analyses of the prc mutant and wild-type ExPEC strains revealed significantly reduced flagellum expression in the absence of Prc, consequently impairing bacterial motility. The prc deletion triggered downregulation of the flhDC operon encoding the master transcriptional regulator of flagellum biogenesis. Overexpressing flhDC restored the prc mutant’s motility and ability to colonize the UT, suggesting that the impaired motility is responsible for attenuated UT colonization of the mutant. Further comparative transcriptome analyses revealed that Prc deficiency activated the σE and RcsCDB signaling pathways. These pathways were responsible for the diminished flhDC expression. Finally, the activation of the RcsCDB system was attributed to the intracellular accumulation of a known Prc substrate Spr in the prc mutant. Spr is a peptidoglycan hydrolase and its accumulation destabilizes the bacterial envelope. Conclusions We demonstrated for the first time that Prc is essential for full ExPEC virulence in UTIs. Our results collectively support the idea that Prc is essential for bacterial envelope integrity, thus explaining how Prc deficiency results in an attenuated ExPEC.

Additional file 1: Table S1. Primers used in this study

We demonstrate an Yb-fiber based pre-chirp managed amplification system that emits 50-MHz, 47-fs pulses with 101.2-W average power. Using chirped mirrors as a compressor, we achieve 98% throughput efficiency.

We demonstrate an energetic ultrafast laser source that simultaneously provides three-color pulses tunable from 925 nm to 1150 nm with energy up to 75 nJ. The repetition-rate can be tuned from 1 to 20 MHz.

OSA continuum 3(7), 1988-1998 (2020). doi:10.1364/OSAC.392981, We incorporate two techniques into pre-chirp managed amplification (PCMA) to achieve high-energy ultrashort pulses with the duration well below 100 fs. Numerical simulations confirmed by our experimental results demonstrate that seeding PCMA with circularly polarized pulses instead of linearly polarized pulses can increase the amplified pulse energy by 1.5 times. We also employ high-dispersion chirped mirrors to compress the amplified pulses with the throughput efficiency as high as 98%. These two techniques allow us to demonstrate an Yb-fiber PCMA system that emits 50-MHz, 47-fs pulses with 101.2-W average power., Published by OSA, Washington, DC

We incorporate circularly polarized seeding pulses and high-dispersion mirror compressor into pre-chirp managed amplification and obtain 50-MHz, 47-fs pulses with 101.2-W average power. The efficiency of the pulse compression is >98%.

A new approach for the total synthesis of the active stilbene dimer dehydro-δ-viniferin has been achieved in 9 steps with methyl 4-hydroxybenzoate and 3,5-dihydroxyacetophenone as starting materials. The key feature of the method is the amberlyst 15-mediated cyclodehydration of α-aryloxyketone. [Formula: see text].

In this study, we applied the Holo-Hilbert spectral analysis (HHSA) method to analyze HRV in electrocardiography (ECG) signals. The HHSA intends to interpret the measured interbeat-interval (IBI) signal as the multiplication of an oscillatory signal (carrier wave) with a modulatory signal (envelope wave). Instantaneous frequency analysis (IFA) was adopted to calculate the frequency modulation (FM) and amplitude modulation (AM) frequencies at each time point. The probability of FM-AM distribution across the whole measured IBI signal was accumulated and displayed on a Holo-Hilbert spectrum (HHS). Twenty healthy subjects were recruited in our ECG study. Each subject was requested to view two video clips, including one relaxing video clip and one horror video clip. We observed the very high-frequency (VHF) band was modulated by a ∼0.05 Hz AM frequency on the calculated HHS. The value of VHF power was significantly decreased (p

Respiration is a crucial vital sign to indicate acidotic state of human body. In this paper, we have developed a Holo-Hilbert spectral analysis (HHSA)-based approach to detect subject’s respiration frequency from wrist photoplethysmogram (PPG) signals. The HHSA is a two-layer EMD architecture which first decomposes the original signal into intrinsic mode functions and then tries to find additive and multiplicative interactions among the participating components. The HHSA enables frequency-modulated (FM) and amplitude-modulated (AM) features of a signal can be comprehensively presented on a Holo-Hilbert spectrum (HHS). With the help of HHSA, subject’s respiration frequency can be identified on HHS by finding the AM frequency with the most prominent amplitude around the FM frequency of heart rate. The efficacy of the proposed method has been demonstrated in two designed experiments. In the first experiment, 75 subjects with ages ranged from 20–80 years old, and the difference between the detected results of proposed method and the readouts of transthoracic impedance plethysmography is 0.04 ± 0.96 breathes-per-minute (brm). In the second experiment, six subjects were requested to breathe at 6, 12, 18, 24 brm, following the pacing rhythms of a metronome. The difference between detected respiration rates and expected breathing rates is 0.01 ± 0.70 brm. The HHSA-based approach has manifested its capability to extract respiration-induced multiplicative component in PPG signal. It avoids the ambiguity of frequency representation in signal multiplication when using traditional additive decomposition methods.

Neural oscillatory activities existing in multiple fre-quency bands usually represent different levels of neurophysiolog-ical meanings, from micro-scale to macro-scale organizations. In this study, we adopted Holo-Hilbert spectral analysis (HHSA) to study the amplitude-modulated (AM) and frequency-modulated (FM) components in sensorimotor Mu rhythm, induced by slow- and fast-rate repetitive movements. The HHSA-based approach is a two-layer empirical mode decomposition (EMD) architecture, which firstly decomposes the EEG signal into a series of frequency-modulated intrinsic mode functions (IMF) and then decomposes each frequency-modulated IMF into a set of amplitude-modulated IMFs. With the HHSA, the FM and AM components were incor-porated with their instantaneous power to achieve full-informa-tional spectral analysis. We observed that the instantaneous power induced by slow-rate movements was significantly higher than that induced by fast-rate movements (p0.01, Wilcoxon signed rank test). The alpha-band AM frequencies induced by slow-rate movements were higher than those induced by fast-rate move-ments, while no statistical difference was found in beta-band AM frequencies. In addition, to study the functional coupling between the primary sensorimotor area and other brain regions, spectral coherence was applied and statistical difference was found in frontal area in slow-rate versus fast-rate movements. The discrep-ancy between slow- and fast-rate movements might be owing to the change of motor functional modes from default mode network (DMN) to automatic timing with the increase of movement rates. The use of HHSA for oscillatory activity analysis can be an effi-cient tool to provide informative interaction among different fre-quency bands.

Manipulation of the emission properties of pure organic molecules through external stimuli is attractive but challenging. Herein, a dual-emissive hexathiobenzene-based molecule is reported with significant aggregation-induced phosphorescence characteristics, and demonstrates reversible switching among blue, green, and yellow phosphorescence by controlling molecular aggregation state or protonation state. Variation of solvent or pH value manipulates the interconversion between fluorescence and phosphorescence, while the change in protonation state in organic solvent switches two short-lived emissions in a controllable manner. Such a controlled manipulation is achieved by the rational design of combining a twisted structure and the proper arrangement of energy gaps among different excited states. This work provides a new design principle for organic molecules with efficient room-temperature phosphorescence and tunable singlet-triplet emissive properties, and contributes to the design and development of smart materials and intelligent optoelectronic devices.

During major earthquake disasters, a lack of preparedness on the part of both officials and citizens can result in serious injuries and fatalities. Indeed, due to the unequal distribution of responsibility, decision-making processes differ sharply between disaster management planners and the general population. Although the potential relationship between earthquake risk perception and adjustment behavior remains subject to debate, humans are indeed capable of responding to disasters and further reducing their risk. Previous discussions emphasized engineering or seismological efforts to mitigate earthquake disaster while attributing less responsibility to government preparedness and individuals’ subjective resilience, although both of these could place people at greater risk of earthquake damage. Therefore, the purpose of this study is to explore and compare the spatial patterns of earthquake disaster probability, subjective resilience, and governmental preparedness. The results show that there are significantly unequal distributions of both subjective resilience on the part of citizens and low preparedness on the part of officials, which might result in serious impacts in a future earthquake disaster. In particular, it is imperative that subjective resilience and governmental preparedness be increased in the northern and southern regions along the Houchiali Fault.

Drag reduction (DR) in plane Couette flow (PCF) induced by the addition of flexible polymers has been studied via direct numerical simulation (DNS). The similarities and differences in the drag reduction features of PCF and plane Poiseuille flow (PPF) have been examined in detail, particularly in regard to the polymer-induced modification of large-scale structures (LSSs) in the near-wall turbulence. Specifically, it has been demonstrated that in the near-wall region, drag-reduced PCF has features similar to those of drag-reduced PPF; however, in the core region, intriguing differences are found between these two drag-reduced shear flows. Chief among these differences is the significant polymer stretch that arises from the enhanced exchanges between elastic potential energy and turbulent kinetic energy and the commensurate observation of peak values of the conformation tensor components $\unicode[STIX]{x1D60A}_{yy}$ and $\unicode[STIX]{x1D60A}_{zz}$ in this region. This finding is in stark contrast to that of drag-reduced PPF where the polymer stretch and the exchanges between elastic potential energy and turbulent kinetic energy in the core region are insignificant; to this end, in drag-reduced PPF, peak values of the conformation tensor components appear in the near-wall region. Therefore, this study paves the way for understanding the underlying flow physics in drag-reduced PCF, particularly in the context of elastic theory. Moreover, the longitudinal large-scale streaks at the channel centre of drag-reduced PCF are greatly strengthened due to the increased production/dissipation ratio; the LSS imprint effects on the near-wall flow of drag-reduced PCF monotonically increase as the Weissenberg number is enhanced.

This work studies the power quality impacts of electric transportation charging including electric buses (EBs) and electric vehicles (EVs) on distribution systems. The stochastic harmonic models for EBs and EVs and the stochastic models for their usage scenarios are built utilising the measured charging data. Based on these models, a power quality analysis method considering the charging uncertainties of EBs and EVs is proposed in this study and then their impacts on distribution systems are investigated. The Monte Carlo simulation is integrated into the proposed method to study the under voltage, overcurrent, voltage unbalance, transformer overload, harmonic current, voltage etc. caused by the stochastic charging of EBs and EVs. An actual distribution system acquired from Taiwan Power Company is taken as an example to validate the practicability of the proposed method. The test results of the proposed stochastic model are compared with those of the conservative model.