Deep learning model to discriminate diverse infection types based on pairwise analysis of host gene expression.

Accurate detection of pathogens, particularly distinguishing between Gram-positive and Gram-negative bacteria, could improve disease treatment. Host gene expression can capture the immune system's response to infections caused by various pathogens. Here, we present a deep neural network model, bvnGPS2, which incorporates the attention mechanism based on a large-scale integrated host transcriptome dataset to precisely identify Gram-positive and Gram-negative bacterial infections as well as viral infections. We performed analysis of 4,949 blood samples across 40 cohorts from 10 countries using our previously designed omics data integration method, iPAGE, to select discriminant gene pairs and train the bvnGPS2. The performance of the model was evaluated on six independent cohorts comprising 374 samples. Overall, our deep neural network model shows robust capability to accurately identify specific infections, paving the way for precise medicine strategies in infection treatment and potentially also for identifying subtypes of other diseases.

Statistical properties for an optically injected chaotic semiconductor laser with a high-pass filter.

Chaotic waveforms with Gaussian distributions are significant for laser-chaos-based applications such as random number generation. By exploring the injection parameter space of the optical injection semiconductor lasers, we numerically investigate the associated probability density functions of the generated chaotic waveforms when different high-pass filters with different cutoff frequencies are used. Our results demonstrate that the chaotic waveforms with Gaussian probability density functions can be obtained once the cutoff frequency of the high-pass filter is larger than the laser relaxation resonance frequency. Especially, we find that the Gaussian probability density function can reach a superhigh coefficient of determination R2 ≥ 99.5% and an ultralow skewness |S|<0.1 in a large parameter space by jointly controlling the injection parameter and cutoff frequency.

Scalable parallel ultrafast optical random bit generation based on a single chaotic microcomb.

Random bit generators are critical for information security, cryptography, stochastic modeling, and simulations. Speed and scalability are key challenges faced by current physical random bit generation. Herein, we propose a massively parallel scheme for ultrafast random bit generation towards rates of order 100 terabit per second based on a single micro-ring resonator. A modulation-instability-driven chaotic comb in a micro-ring resonator enables the simultaneous generation of hundreds of independent and unbiased random bit streams. A proof-of-concept experiment demonstrates that using our method, random bit streams beyond 2 terabit per second can be successfully generated with only 7 comb lines. This bit rate can be easily enhanced by further increasing the number of comb lines used. Our approach provides a chip-scale solution to random bit generation for secure communication and high-performance computation, and offers superhigh speed and large scalability.

Signature of quantum criticality in cuprates by charge density fluctuations.

The universality of the strange metal phase in many quantum materials is often attributed to the presence of a quantum critical point (QCP), a zero-temperature phase transition ruled by quantum fluctuations. In cuprates, where superconductivity hinders direct QCP observation, indirect evidence comes from the identification of fluctuations compatible with the strange metal phase. Here we show that the recently discovered charge density fluctuations (CDF) possess the right properties to be associated to a quantum phase transition. Using resonant x-ray scattering, we studied the CDF in two families of cuprate superconductors across a wide doping range (up to p = 0.22). At p* ≈ 0.19, the putative QCP, the CDF intensity peaks, and the characteristic energy Δ is minimum, marking a wedge-shaped region in the phase diagram indicative of a quantum critical behavior, albeit with anomalies. These findings strengthen the role of charge order in explaining strange metal phenomenology and provide insights into high-temperature superconductivity.

Prevailing Charge Order in Overdoped La_{2-x}Sr_{x}CuO_{4} beyond the Superconducting Dome.

The extremely overdoped cuprates are generally considered to be Fermi liquid metals without exotic orders, whereas the underdoped cuprates harbor intertwined states. Contrary to this conventional wisdom, using Cu L_{3}-edge and O K-edge resonant x-ray scattering, we reveal a charge order (CO) correlation in overdoped La_{2-x}Sr_{x}CuO_{4} (0.35≤x≤0.6) beyond the superconducting dome. This CO has a periodicity of ∼6 lattice units with correlation lengths of ∼20 lattice units. It shows similar in-plane momentum and polarization dependence and dispersive excitations as the CO of underdoped cuprates, but its maximum intensity differs along the c direction and persists up to 300 K. This CO correlation cannot be explained by the Fermi surface instability and its origin remains to be understood. Our results suggest that CO is prevailing in the overdoped metallic regime and requires a reassessment of the picture of overdoped cuprates as weakly correlated Fermi liquids.

bvnGPS: a generalizable diagnostic model for acute bacterial and viral infection using integrative host transcriptomics and pretrained neural networks.

MOTIVATION: The confusion of acute inflammation infected by virus and bacteria or noninfectious inflammation will lead to missing the best therapy occasion resulting in poor prognoses. The diagnostic model based on host gene expression has been widely used to diagnose acute infections, but the clinical usage was hindered by the capability across different samples and cohorts due to the small sample size for signature training and discovery. RESULTS: Here, we construct a large-scale dataset integrating multiple host transcriptomic data and analyze it using a sophisticated strategy which removes batch effect and extracts the common information from different cohorts based on the relative expression alteration of gene pairs. We assemble 2680 samples across 16 cohorts and separately build gene pair signature (GPS) for bacterial, viral, and noninfected patients. The three GPSs are further assembled into an antibiotic decision model (bacterial-viral-noninfected GPS, bvnGPS) using multiclass neural networks, which is able to determine whether a patient is bacterial infected, viral infected, or noninfected. bvnGPS can distinguish bacterial infection with area under the receiver operating characteristic curve (AUC) of 0.953 (95% confidence interval, 0.948-0.958) and viral infection with AUC of 0.956 (0.951-0.961) in the test set (N = 760). In the validation set (N = 147), bvnGPS also shows strong performance by attaining an AUC of 0.988 (0.978-0.998) on bacterial-versus-other and an AUC of 0.994 (0.984-1.000) on viral-versus-other. bvnGPS has the potential to be used in clinical practice and the proposed procedure provides insight into data integration, feature selection and multiclass classification for host transcriptomics data. AVAILABILITY AND IMPLEMENTATION: The codes implementing bvnGPS are available at https://github.com/Ritchiegit/bvnGPS. The construction of iPAGE algorithm and the training of neural network was conducted on Python 3.7 with Scikit-learn 0.24.1 and PyTorch 1.7. The visualization of the results was implemented on R 4.2, Python 3.7, and Matplotlib 3.3.4.

Towards High-Performance Supercapacitor Electrodes via Achieving 3D Cross-Network and Favorable Surface Chemistry.

Transition metal phosphides/phosphates (TMPs) are considered appealing electrode materials in energy-related fields, especially in supercapacitors. However, the dilemma of inadequate electrode kinetics and dimensional unreliability evoked by a huge volume variation during cycling significantly plagues their progress. To mitigate this issue, in this work, a 3D cross-network in situ assembled via self-derived N-doped carbon hybrid Ni-Co-P/POx 2D sheets is fabricated. Particularly, high-Fermi-level N-doped carbon well confines Ni-Co-P/POx nanoparticles at the molecular level, and N-doping leads to redistribution of spin/electron density in the carbon skeleton, effectively regulating the electron environment of nearby Ni-Co-based moieties, resulting in a relatively lower surface work function, as known via experimental and Kelvin probe force microscopy (KPFM) results, which favors electron flee from the electrode surface and facilitates electron transport toward a rapid supercapacitor response. Moreover, the well-defined 3D cross-network architectures featured with in-plane pores and interconnected with each other can provide more ion/electron transfer pathways and 2D sheets with excellent surface chemistry available for sustainable ion/electron mobility, synergistically affording the favorable electrode kinetics. Accordingly, the resultant Ni-Co-P/POx@NC electrode shows admirable specific capacitance, excellent rate survivability, and long-term cyclability. The as-assembled asymmetric device exhibits remarkable energy and power outputs (48.5 Wh kg-1 and 7500 W kg-1), superior to many reported devices. Furthermore, our devices possess the prominent ability to power a commercial electronic thermometer for 1560 s at least, showcasing superb application prospects.

Overexpression of centromere protein K (CENPK) gene in Differentiated Thyroid Carcinoma promote cell Proliferation and Migration.

Differentiated thyroid carcinoma (DTC) is one of the most common malignant tumors. Increasing evidence indicates that centromere protein K(CENPK) may play a key role in promoting carcinogenesis. The expression, biological functions, and clinical significance of CENPK in DTC are still unclear. The CENPK expression in the DTC specimen was confirmed using quantitative real-time PCR and Western blot. The expression of CENPK was silenced and promoted by lentivirus-mediated transfection with shRNA sequences or CENPK plasmid targeting CENPK in TPC1 and FTC-133 cells, respectively. Colony formation, Cell Counting Kit-8 (CCK-8), Transwell invasion, and scratch assays were performed to assess the malignant biological properties of FTC-133 and TPC1 cells. Tumorigenicity assay was performed using C57BL/6 mice to explore the influence of CENPK on the growth of TPC1. The present work suggested that the expression of CENPK remarkably increased in follicular thyroid cancer and papillary thyroid cancer  tissue samples at the mRNA level. Immunohistochemical staining also showed consistent results at the protein level. In addition, CENPK mRNA expression level showed great value in diagnosis of DTC. Knockdown of CENPK significantly inhibited the invasion and migration of TPC1 and FTC-133 cells. In contrast, CENPK overexpression promoted invasion and migration of TPC1 and FTC-133 cells. Knockdown and overexpression of CENPK showed consistent effect on DTC tumor growth and expression of Ki-67 invivo. Our results indicated that CENPK was evidently upregulated in DTC. Knocking down CENPK suppressed TPC1 cell proliferation, invasion and migration. Targeting the CENPK may be anovel therapeutic method for DTC.

[Comparison the application of 3D versus 2D laparoscopic thyroidectomy via modified chest and mammary areola approach].

OBJECTIVE: To explore the safety, effectiveness and feasibility of 3D laparoscopy in thyroidectomy via modified chest and mammary areola approach comparing with 2D. METHOD: Twenty six cases received 3D laparoscopic thyroidectomy (3D group) and 34 cases experienced 2D (2D group). We compared the indexes about general status, operation time, operative blood loss, duration and overall volume of postoperative drainage, complications, etc between two groups. RESULT: Eight cases of thyroid cancer were detected in 3D group and 3 cases in 2D group. While there was no statistical difference between two groups with respect to other observation indexes such as other general status, operation time, operative blood loss, duration and overall volume of postoperative drainage, complications, etc. CONCLUSION: 3D laparoscopic thyroidectomy via modified chest and mammary areola approach is a safe, effective and feasible procedure, and it may substitute the place of 2D in the future.

[122 cases of endoscopic thyroidectomies through modified chest and mammary areola approach].

OBJECTIVE: To explore the safety and feasibility of endoscopic thyroidectomies through modified chest and mammary areola approach. METHOD: We retrospectively analyzed 122 cases of endoscopic thyroidectomies through a modified chest and mammary areola approach without extensive dissection of thoracic flap. The information about general status, surgical procedures and techniques, complications, etc. were summarized and discussed. RESULT: One hundred and twenty-one cases were operated successfully while 1 case was converted to video-assisted thyroidectomy through infraclavicular approach. The maximum diameter of the mass was (2.05 ± 1.06) cm, mean operation time was (88.61 ± 27.87) min, the operative blood loss was (31.23 ± 16.14) ml, duration of postoperative drainage was (3.54 ± 0.88) d and overall drainage volume was (139.09 ± 95.93) ml. Parathyroid glands were detected in specimens of 9 cases while no case of permanent postoperative hypocalcaemia was displayed. 6 cases of hoarseness were developed. One case experienced conversion surgery, all the others obtained satisfactory cosmetic result. All cases were followed up for 0-24 months without relapse and metastasis of the disease. CONCLUSION: Endoscopic thyroidectomy via a modified chest and breast areola approach can facilitated the procedure and avoid extensive dissection of thoracic flap, and proved to be safe and effective.

[Effect of quercetin on doxorubicin-induced expression of MDR1 gene in HL-60 cells].

OBJECTIVE: Leukemia cells can acquire a multidrug resistant (MDR) phenotype in response to a wide variety of chemotherapeutic agents including doxorubicin (Dox). In addition to the constitutive expression in the leukemia prior to chemotherapy, a complex phenotype of pleiotropic resistance is presented in the residual or recurrent leukemia. Recent studies showed Dox-induced coexpression of COX2 and MDR1 genes in human leukaemia cells, and whether Dox-induced MDR1 up-regulation in acute leukaemia cells is dependent on COX2-transcriptional activity and thus might be overcome or prevented with COX2-promotor inhibitor quercetin interfering with COX2 expression and activity. This study was purposed to investigate the impacts of quercetin on Dox-induced mRNA expression of MDR1 and COX2 genes in HL-60 leukemia cells. METHODS: The MDR1 and COX2 mRNA expression in HL-60 cells was detected by RT-PCR; the prostaglandin E2 (PGE2) release was measured by ELISA; the cytotoxicity of Dox was determined by MTT test. RESULTS: The incubation of HL-60 cells with Dox not only up-regulated MDR1 mRNA, but also COX2 mRNA expression, and after co-incubation with quercetin or celecoxib, Dox-induced overexpression of MDR1 and COX2 mRNA were reduced by quercetin, not by celecoxib, whereas PGE2 release was significantly decreased with subsequent enhancement of Dox cytotoxic efficacy by both of them. CONCLUSIONS: Dox-induced MDR1 up-regulation may be dependent on COX2-transcriptional activity, not PGE2, suggesting that the existence of causal link between COX2 and MDR1 expression induced by Dox, and modulation of COX2 transcriptional expression by quercetin would not only sensitize leukemia cells to Dox, but also prevent the acquisition of MDR during chemotherapy.

Screening and comparison of differentially expressed genes between one MDR-TB strain and the virulent M. tuberculosis H37Rv.

To screen and compare the differentially expressed genes between one MDR-TB strain separated from one child patient and the virulent Mycobacterium tuberculosis H37Rv, suppression subtractive hybridization (SSH) technology was used to build a library of cDNAs that were differentially expressed in the MDR and H37Rv. From this cDNA library, genes that were expressed in the MDR-TB but not in the H37Rv were selected for gene sequencing and homology analysis; 113 positive clones were obtained, their cDNA fragments were sequenced, and homology analysis was performed. Four novel sequences were identified. The results provide a partial list of genes differentially expressed in MDR-TB and four novel genes were found. Identification of these genes may contribute to our understanding of MDR-TB development.

[Genotyping of 210 Mycobacterium tuberculosis strains with Spoligotyping and MIRU-VNTR among pediatric tuberculosis patients in Chongqing].

OBJECTIVE: To evaluate the application of spacer oligonucleotide typing (Spoligotyping) and mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) analysis in the molecular-epidemiological study of tuberculosis and to discuss the characteristics of pediatric Mycobacterium (M.) tuberculosis strains in Chongqing. METHODS: M. tuberculosis strains isolated and typed by Spoligotyping and MIRU-VNTR respectively, from the children patients in Chongqing and to compare the results from both methods, epidemiologically. RESULTS: By means of Spoligotyping, 210 clinical isolates were divided into 2 gene groups, displaying 44 genotypes. Among them, the biggest group was M. tuberculosis Beijing family, including 130 strains (61.90%), using the Spoligotyping. From the results of MIRU-VNTR, 24 loci showed different polymorphism and the HGI of different loci set (12 old loci, 15 basic loci and 24-loci set) increased accordingly. The subtle difference in HGI was originated from one locus ETR-B, which was included in the 24-locus system. The diversity of each loci and MIRU-VNTR set for non-Beijing genotype strains was higher than that of the Beijing genotype strains. CONCLUSION: In this study, it was preliminarily confirmed the existence of high polymorphism of M. tuberculosis while the Beijing Family was the main genotype and main prevalent strain in children of Chongqing area. Spoligotyping prior to 15-locus with ETR-B combination seemed more suitable for the massive epidemiological investigation of pediatric tuberculosis patients.

Determination of glutamic acid by an oscillating chemical reaction using the analyte pulse perturbation technique.

An analytical method for the determination of glutamic acid by the sequential perturbation caused by different amounts of glutamic acid on the oscillating chemical system involving the Cu(II)-catalyzed oscillating reaction between hydrogen peroxide and sodium thiocyanate in an alkaline medium is proposed. The method relies on the linear relationship between the changes in the oscillation amplitude of the chemical system and the concentration of glutamic acid. The reaction is implemented in a continuous-flow stirred-tank reactor, and changes in the oscillation amplitude on each perturbation are proportional to the glutamic acid concentration. The use of the analyte pulse perturbation (APP) technique permits sequential determinations on the same oscillating system owing to the expeditiousness with which the steady state is regained after each perturbation. The dynamic range lies between 2.5x10(-6) and 3.2x10(-4) M of glutamic acid, with the regression coefficient is 0.9987. The precision is excellent (less than 0.68% as relative standard deviation (R.S.D.)). Some aspects of the potential mechanism of action of glutamic acid on the oscillating system are discussed.