Diagnostic Potential of Serum Glycome Analysis in Lung Cancer: A Glycopattern Study.

Lung cancer is the leading cause of cancer-related death, with high morbidity and mortality rates due to the lack of reliable methods for diagnosing lung cancer at an early stage. Low-dose computed tomography can help detect abnormal areas in the lungs, but only 16% of cases are diagnosed early. Tests for lung cancer markers are often employed to determine genetic expression or mutations in lung carcinogenesis. Serum glycome analysis is a promising new method for early lung cancer diagnosis as glycopatterns exhibit significant differences in lung cancer patients. In this study, we employed a solid-phase chemoenzymatic method to systematically compare glycopatterns in benign cases, adenocarcinoma before and after surgery, and advanced stages of adenocarcinoma. Our findings indicate that serum high-mannose levels are elevated in both benign cases and adenocarcinoma, while complex N-glycans, including fucose and 2,6-linked sialic acid, are downregulated in the serum. Subsequently, we developed an algorithm that utilizes 16 altered N-glycans, 7 upregulated and 9 downregulated, to generate a score based on their intensity. This score can predict the stages of cancer progression in patients through glycan characterization. This methodology offers a potential means of diagnosing lung cancer through serum glycome analysis.

Novel Approach to Enriching Glycosylated RNAs: Specific Capture of GlycoRNAs via Solid-Phase Chemistry.

Ribonuclease (RNA) modifications can alter cellular function and lead to differential immune responses by acting as discriminators between RNAs from different phyla. RNA glycosylation has recently been observed at the cell surface, and its dysregulation in disease may change RNA functions. However, determining which RNA substrates can be glycosylated remains to be explored. Here, we develop a solid-phase chemoenzymatic method (SPCgRNA) for targeting glycosylated RNAs, by which glycosylated RNA substrates can be specifically recognized. We found the differential N-glycosylation of small RNAs in hTERT-HPNE and MIA PaCa-2 cancer cells using SPCgRNA. RNA-Seq showed that the changes in glyco-miRNAs prepared from SPCgRNA were consistent with those of traditional methods. The KEGG signaling pathway analysis revealed that differential miRNA glycosylation can affect tumor cell proliferation and survival. Further studies found that NGI-1 significantly inhibited the proliferation, migration, and circulation of MIA PaCa-2 and promoted cell apoptosis. In addition, ß-1,4-galactosyltransferase 1 (B4GALT1) not only affected the expression level of glycosylated miRNAs hsa-miR-21-5p but also promoted cell apoptosis and inhibited the cell cycle possibly through the p53 signaling pathway, while B4GALT1 and p53 were also affected following the hsa-miR-21-5p increase. These results suggest that B4GALT1 may catalyze miRNAs glycosylation, which further promotes cancer cell progression.

Improving Ponzi Scheme Contract Detection Using Multi-Channel TextCNN and Transformer.

With the development of blockchain technologies, many Ponzi schemes disguise themselves under the veil of smart contracts. The Ponzi scheme contracts cause serious financial losses, which has a bad effect on the blockchain. Existing Ponzi scheme contract detection studies have mainly focused on extracting hand-crafted features and training a machine learning classifier to detect Ponzi scheme contracts. However, the hand-crafted features cannot capture the structural and semantic feature of the source code. Therefore, in this study, we propose a Ponzi scheme contract detection method called MTCformer (Multi-channel Text Convolutional Neural Networks and Transofrmer). In order to reserve the structural information of the source code, the MTCformer first converts the Abstract Syntax Tree (AST) of the smart contract code to the specially formatted code token sequence via the Structure-Based Traversal (SBT) method. Then, the MTCformer uses multi-channel TextCNN (Text Convolutional Neural Networks) to learn local structural and semantic features from the code token sequence. Next, the MTCformer employs the Transformer to capture the long-range dependencies of code tokens. Finally, a fully connected neural network with a cost-sensitive loss function in the MTCformer is used for classification. The experimental results show that the MTCformer is superior to the state-of-the-art methods and its variants in Ponzi scheme contract detection.

An Empirical Study of Training Data Selection Methods for Ranking-Oriented Cross-Project Defect Prediction.

Ranking-oriented cross-project defect prediction (ROCPDP), which ranks software modules of a new target industrial project based on the predicted defect number or density, has been suggested in the literature. A major concern of ROCPDP is the distribution difference between the source project (aka. within-project) data and target project (aka. cross-project) data, which evidently degrades prediction performance. To investigate the impacts of training data selection methods on the performances of ROCPDP models, we examined the practical effects of nine training data selection methods, including a global filter, which does not filter out any cross-project data. Additionally, the prediction performances of ROCPDP models trained on the filtered cross-project data using the training data selection methods were compared with those of ranking-oriented within-project defect prediction (ROWPDP) models trained on sufficient and limited within-project data. Eleven available defect datasets from the industrial projects were considered and evaluated using two ranking performance measures, i.e., FPA and Norm(Popt). The results showed no statistically significant differences among these nine training data selection methods in terms of FPA and Norm(Popt). The performances of ROCPDP models trained on filtered cross-project data were not comparable with those of ROWPDP models trained on sufficient historical within-project data. However, ROCPDP models trained on filtered cross-project data achieved better performance values than ROWPDP models trained on limited historical within-project data. Therefore, we recommended that software quality teams exploit other project datasets to perform ROCPDP when there is no or limited within-project data.

Influence of the structure and composition of Fe-Mn binary oxides on rGO on As(III) removal from aquifers.

Fe-Mn binary oxide (FMBO) possesses high efficiency for As(III) abatement based on the good adsorption affinity of iron oxide and the oxidizing capacity of Mn(IV), and the composition and structure of FMBO play important roles in this process. To compare the removal performance and determine the optimum formula for FMBO, magnetic graphene oxide (MRGO)-FMBO and MRGO-MnO2 were synthesized with MRGO as a carrier to improve the dispersity of the adsorbents in aquifers and achieve magnetic recycling. Results indicated that MRGO-FMBO had higher As(III) removal than that of MRGO-MnO2, although the ratios of Fe and Mn were similar, because the binary oxide of Fe and Mn facilitated electron transfer from Mn(IV) to As(III), while the separation of Mn and Fe on MRGO-MnO2 restricted the process. The optimal stoichiometry x for MRGO-FMBO (MnxFe3-xO4) was 0.46, and an extraordinary adsorption capacity of 24.38 mg/g for As(III) was achieved. MRGO-FMBO showed stable dispersive properties in aquifers, and exhibited excellent practicability and reusability, with a saturation magnetization of 7.6 emu/g and high conservation of magnetic properties after 5 cycles of regeneration and reuse. In addition, the presence of coexisting ions would not restrict the practical application of MRGO-FMBO in groundwater remediation. The redox reactions of As(III) and Mn(IV) on MRGO-FMBO were also described. The deprotonated aqueous As(III) on the surface of MRGO-FMBO transferred electrons to Mn(IV), and the formed As(V) oxyanions were bound to ferric oxide as inner-sphere complexes by coordinating their "-OH" groups with Mn(IV) oxides at the surface of MRGO-FMBO. This work could provide new insights into high-performance removal of As(III) in aquifers.

Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1.

BACKGROUND AND AIM: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. METHODS: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. RESULTS: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9-99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8-100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. CONCLUSIONS: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.

[Analysis of XPS in the Removal of Cr(â ¥) from Groundwater with rGO-nZâ ¥].

Iron nanoparticles are widely used in heavy metal ions removal from water, but because of the characteristics of easily aggregation and transference in the groundwater, remediation effect was reduced. GO with a negative charge containing oxygen-containing functional groups on the surfaces of graphene, are widely used for the removal of heavy metal ions from water, but it has little on remediating hexavalent chromium (Cr2O2-7, CrO2-4) with negatively charged electrons. Therefore, rGO-nZⅥ was synthesized via liquid phase reduction method to overcome the aggregation and transference of FeO, changing the negative charged Cr2O2-7 or CrO2-4 to positive charged Cr3+. The material behavior characteristics of Cr(Ⅵ) removal were discussed. X-ray diffraction (XRD) and transmission electron microscopy (TEM) were used to test the prepared rGO-nZⅥ. Results indicated that nZⅥ was successfully loaded on the surface of GO, and the shape of the particles was approximate ball and the granular diameter ranged from 20 to 100 nm. Removal efficiency of Cr(Ⅵ) (40 mg·L-1) from water was nearly 100% within 24 h using rGO-nZⅥ. X-ray photoelectron spectroscopy (XPS) analyses using the XPSPEAK41 program indicated that FeO firstly reduced negatively charged Cr(Ⅵ) to positively charged Cr(Ⅲ) by providing electron, then the chromium in the solution can be removed as chromium hydroxide (Cr(OH)3) by a hydrolysis precipitation process. As the reaction progress, materials charges were changing, which benefited adsorpting Cr(Ⅵ). After 24 h reaction, the residual nZⅥ loading on rGO-nZⅥ remained, which showed the potential of sequentially remediating contamination. The results showed important theoretical value and practicability.

Randomized comparison of daclatasvir + asunaprevir versus telaprevir + peginterferon/ribavirin in Japanese hepatitis C virus patients.

BACKGROUND AND AIM: Daclatasvir combined with asunaprevir is the first all-oral, ribavirin-free treatment of hepatitis C virus genotype 1b infection in Japan. This study compared the efficacy and safety of daclatasvir plus asunaprevir versus telaprevir plus peginterferon/ribavirin in Japanese treatment-naive patients infected with hepatitis C virus genotype 1b. METHODS: Treatment-naive patients (20-70 years; baseline viral load, ≥ 100,000 IU/mL) were randomly assigned (stratified by IL28B rs8099917 TT/non-TT status) to receive either daclatasvir 60 mg tablets once daily and asunaprevir 100 mg softgel capsules twice daily for 24 weeks or telaprevir 750 mg (3 × 250 mg tablets) three times daily for 12 weeks and peginterferon/ribavirin per Japanese prescribing information for 24 weeks. A cohort of prior relapsers to peginterferon/ribavirin (20-75 years; baseline viral load, ≥ 100,000 IU/mL) received daclatasvir plus asunaprevir. RESULTS: In treatment-naive patients, sustained virologic response at post-treatment week 12 in daclatasvir plus asunaprevir recipients was non-inferior (treatment difference, +25.8% in favor of daclatasvir plus asunaprevir) and higher (89.1%, 106/119) than telaprevir plus peginterferon/ribavirin recipients (62.2%, 69/111); sustained viral response was achieved in 95.5% (n = 21/22) of relapsers. Numerically, fewer patients receiving daclatasvir plus asunaprevir compared with telaprevir plus peginterferon/ribavirin experienced serious adverse events (4.2% vs. 5.4%), adverse events leading to discontinuation of any drug (5.0% vs. 62.2%), grade 3/4 treatment-related adverse events (14.3% vs. 72.1%), rash-related events (0% vs. 13.5%), or anemia (0% vs. 47.7%). CONCLUSION: Marked differences were observed in the efficacy and safety profile of daclatasvir in combination with asunaprevir, compared with telaprevir plus peginterferon/ribavirin.

Image restoration method for longitudinal laser tomography based on degradation matrix estimation.

Target images captured by longitudinal laser tomography are usually degraded by nonuniform laser beams transmitting through inhomogeneous scattering mediums. An image restoration method with a total variation model is proposed for eliminating the main influence of inhomogeneous scattering mediums from degraded target images. Based on the physical signal relevance between the target layer and the scattering medium layer, the degradation matrix of the target image is approximately estimated by the specified backscattering images of the scattering mediums. Simulations and experiments are performed to verify the validity and feasibility of the proposed method, and all the results demonstrate that the proposed model works well and helps us to achieve the real target images, which represent the reflectivity distributions of the targets standing behind the inhomogeneous scattering mediums and which will benefit target recognition and identification.

Simultaneous measurement of pressure and temperature using dual-path distributed Brillouin sensor.

A sensing technique called a dual-path distributed Brillouin sensor (D-DBS) is proposed for simultaneous measurement of pressure and temperature. The D-DBS consists of a pair of sensing fibers, which are designed with different pressure and temperature coefficients of Brillouin frequency shift (BFS) by taking advantage of different fiber coatings. The highlight of this technique is to resolve the problem of the pressure-temperature cross sensitivity of the BFS within the optical fibers. The validation experiment shows satisfactory results, and it is indicated theoretically that the expected precisions of pressure and temperature are less than 0.25 MPa and 0.28°C, respectively.

Synthesis, characterization and photocatalytic activity of new photocatalyst ZnBiSbO4 under visible light irradiation.

In this paper, ZnBiSbO4 was synthesized by a solid-state reaction method for the first time. The structural and photocatalytic properties of ZnBiSbO4 had been characterized by X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, transmission electron microscope and UV-visible spectrometer. ZnBiSbO4 crystallized with a pyrochlore-type structure and a tetragonal crystal system. The band gap of ZnBiSbO4 was estimated to be 2.49 eV. The photocatalytic degradation of indigo carmine was realized under visible light irradiation with ZnBiSbO4 as a catalyst compared with nitrogen-doped TiO2 (N-TiO2) and CdBiYO4. The results showed that ZnBiSbO4 owned higher photocatalytic activity compared with N-TiO2 or CdBiYO4 for the photocatalytic degradation of indigo carmine under visible light irradiation. The reduction of the total organic carbon, the formation of inorganic products, SO4(2-) and NO3(-), and the evolution of CO2 revealed the continuous mineralization of indigo carmine during the photocatalytic process. One possible photocatalytic degradation pathway of indigo carmine was obtained. The phytotoxicity of the photocatalytic-treated indigo carmine (IC) wastewater was detected by examining its effect on seed germination and growth.

Interference Morphology of Free-Growing Tendrils and Application of Self-Locking Structures.

Organisms can adapt to various complex environments by obtaining optimal morphologies. Plant tendrils evolve an extraordinary and stable spiral morphology in the free-growing stage. By combining apical and asymmetrical growth strategies, the tendrils can adjust their morphology to wrap around and grab different supports. This phenomenon of changing tendril morphology through the movement of growth inspires a thoughtful consideration of the laws of growth that underlie it. In this study, tendril growth is modeled based on the Kirchhoff rod theory to obtain the exact morphological equations. Based on this, the movement patterns of the tendrils are investigated under different growth strategies. It is shown that the self-interference phenomenon appears as the tendril grows, allowing it to hold onto its support more firmly. In addition, a finite element model is constructed using continuum media mechanics and following the finite growth theory to simulate tendril growth. The growth morphology and self-interference phenomenon of tendrils are observed visually. Furthermore, an innovative class of fluid elastic actuators is designed to verify the growth phenomena of tendrils, which can realize the wrapping and locking functions. Several experiments are conducted to measure the end output force and the smallest size that can be clamped, and the output efficiency of the elastic actuator and the optimal working pressure are verified. The results presented in this study could reveal the formation law of free tendril spiral morphology and provide an inspiring idea for the programmability and motion control of bionic soft robots, with promising applications in the fields of underwater rescue and underwater picking.

Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas. / èƒ°è ºç™Œç»†èƒžå’Œè¡€æ¸ å®Œæ•´è›‹ç™½è´¨N-糖基化特征的质谱分析.

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Intrinsic Defect-Driven Synergistic Synaptic Heterostructures for Gate-Free Neuromorphic Phototransistors.

The optoelectronic synaptic devices based on two-dimensional (2D) materials offer great advances for future neuromorphic visual systems with dramatically improved integration density and power efficiency. The effective charge capture and retention are considered as one vital prerequisite to realizing the synaptic memory function. However, the current 2D synaptic devices are predominantly relied on materials with artificially-engineered defects or intricate gate-controlled architectures to realize the charge trapping process. These approaches, unfortunately, suffer from the degradation of pristine materials, rapid device failure, and unnecessary complication of device structures. To address these challenges, an innovative gate-free heterostructure paradigm is introduced herein. The heterostructure presents a distinctive dome-like morphology wherein a defect-rich Fe7S8 core is enveloped snugly by a curved MoS2 dome shell (Fe7S8@MoS2), allowing the realization of effective photocarrier trapping through the intrinsic defects in the adjacent Fe7S8 core. The resultant neuromorphic devices exhibit remarkable light-tunable synaptic behaviors with memory time up to ≈800 s under single optical pulse, thus demonstrating great advances in simulating visual recognition system with significantly improved image recognition efficiency. The emergence of such heterostructures foreshadows a promising trajectory for underpinning future synaptic devices, catalyzing the realization of high-efficiency and intricate visual processing applications.

Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options.

BACKGROUND & AIMS: Improved therapeutic options for chronic hepatitis C virus (HCV) infection are needed for patients who are poor candidates for treatment with current regimens due to anticipated intolerability or low likelihood of response. METHODS: In this open-label, phase 2a study of Japanese patients with chronic HCV genotype 1b infection, 21 null responders (<2 log10 HCV RNA reduction after 12 weeks of peginterferon/ribavirin) and 22 patients intolerant to or medically ineligible for peginterferon/ribavirin therapy received dual oral treatment for 24 weeks with the NS5A replication complex inhibitor daclatasvir (DCV) and the NS3 protease inhibitor asunaprevir (ASV). The primary efficacy end point was sustained virologic response at 12 weeks post-treatment (SVR12). RESULTS: Thirty-six of 43 enrolled patients completed 24 weeks of therapy. Serum HCV RNA levels declined rapidly, becoming undetectable in all patients on therapy by week 8. Overall, 76.7% of patients achieved SVR12 and SVR24, including 90.5% of null responders and 63.6% of ineligible/intolerant patients. There were no virologic failures among null responders. Three ineligible/intolerant patients experienced viral breakthrough and four relapsed post-treatment. Diarrhea, nasopharyngitis, headache, and ALT/AST increases, generally mild, were the most common adverse events; three discontinuations before week 24 were due to adverse events that included hyperbilirubinemia and transaminase elevations (two patients). CONCLUSIONS: Dual therapy with daclatasvir and asunaprevir, without peginterferon/ribavirin, was well tolerated and achieved high SVR rates in two groups of difficult-to-treat patients with hepatitis C virus genotype 1b infection.

Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B.

For patients undergoing liver transplantation (LT) for hepatitis B virus (HBV)-related liver disease, the current standard of care for preventing reinfection of the allograft is nucleoside analogue therapy combined with hepatitis B immune globulin (HBIG). Entecavir has demonstrated high efficacy and a favorable safety profile for chronic hepatitis B (CHB) treatment, but data for patients undergoing HBV-related LT are limited. This study assessed the safety and efficacy of entecavir combined with various HBIG regimens after CHB-related LT. In this phase 3b, single-arm, open-label study, 65 patients undergoing LT for CHB-related liver disease with an HBV DNA load <172 IU/mL at LT received entecavir (1.0 mg daily) for 72 weeks after LT. The primary endpoint was the proportion of evaluable patients (treated for ≥4 weeks) with virological recurrence (HBV DNA level ≥50 IU/mL) through week 72. Concomitant HBIG therapy was received by 64 of the 65 enrolled patients, and 44% of these patients received high-dose HBIG (any HBIG dose in the specified interval ≥10,000 IU). Through week 72, all 61 patients evaluable for the efficacy analysis had undetectable HBV DNA. The Kaplan-Meier estimate of patients without hepatitis B surface antigen (HBsAg) recurrence at week 72 was 0.9655. Two patients experienced a reappearance of HBsAg, but both remained HBV DNA(-) until the last follow-up. The frequency and nature of adverse events were consistent with those expected for this patient population. Serum creatinine increments ≥0.3 mg/dL and ≥0.5 mg/dL occurred in 62% and 39% of the patients, respectively, and all of these patients received calcineurin inhibitor therapy. In conclusion, in this population of patients treated with entecavir after CHB-related LT, entecavir was well tolerated and effective in maintaining viral suppression, even in individuals who experienced a reappearance of HBsAg.

[Reconstitution of humoral immunity by the transplantation of human umbilical cord blood CD34+ cells into NOD/ SCID mice].

OBJECTIVE: To investigate the immune reconstitution by the transplantation of human umbilical cord blood CD34+ cells in the NOD/SCID mouse. METHODS: Mononuclear cells (MNC) were isolated from human fresh cord blood and CD34+ hematopoietic stem cells were selected by magnetic activated cell sorting method. The selected cells were transplanted via tail vein injection into 16 NOD/SCID mice after sublethal whole-body irradiation. Four mice were sacrificed respectively at 4th, 6th, 8th and 10th week after the transplantation, the harvested spleen and peripheral blood cells were used to cell phenotype analysis and humoral immune analysis, respectively. There were 14 mice in another two groups, 7 mice did not receive the transplantation after irradiation, 7 were used as blank control (no irradiation, no transplantation). RESULTS: The mice without transplantation all died within 2 weeks after irradiation. The survival rate of the mice with transplantation was 37.5% at 6th week after the irradiation, while the survival rate of blank control was 100%. At 4th, 6th, 8th and 10th week, the percentage of human CD45+ cells in transplantation group were 4.7 +/- 1.23, 9.22 +/- 2.07, 12.34 +/- 2.38, 8.14 +/- 2.36, respectively, and the percentage of CD19+ B lymphocytes were 1.07 +/- 0.50, 2.17 +/- 0.95, 3.34 +/- 0.90, 1.67 +/- 0.90, respectively. 10 weeks after the transplantation, human CD19+ B lymphocytes distribution were found in the transplanted mice spleen. CONCLUSION: The human-mouse chimeric immune model can be built in irradiated NOD/ SCID mice by the transplantation of human cord blood CD34+ cells. CD34+ cell differentiation declined with time, which might be due to the lack of appropriate cytokines.

Recent development of analytical methods for disease-specific protein O-GlcNAcylation.

The enzymatic modification of protein serine or threonine residues by N-acetylglucosamine, namely O-GlcNAcylation, is a ubiquitous post-translational modification that frequently occurs in the nucleus and cytoplasm. O-GlcNAcylation is dynamically regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase, and regulates nearly all cellular processes in epigenetics, transcription, translation, cell division, metabolism, signal transduction and stress. Aberrant O-GlcNAcylation has been shown in a variety of diseases, including diabetes, neurodegenerative diseases and cancers. Deciphering O-GlcNAcylation remains a challenge due to its low abundance, low stoichiometry and extreme lability in most tandem mass spectrometry. Separation or enrichment of O-GlcNAc proteins or peptides from complex mixtures has been of great interest because quantitative analysis of protein O-GlcNAcylation can elucidate their functions and regulatory mechanisms in disease. However, valid and specific analytical methods are still lacking, and efforts are needed to further advance this direction. Here, we provide an overview of recent advances in various analytical methods, focusing on chemical oxidation, affinity of antibodies and lectins, hydrophilic interaction, and enzymatic addition of monosaccharides in conjugation with these methods. O-GlcNAcylation quantification has been described in detail using mass-spectrometric or non-mass-spectrometric techniques. We briefly summarized dysregulated changes in O-GlcNAcylation in disease.

Generation of dark hollow femtosecond pulsed beam by phase-only liquid crystal spatial light modulator.

Based on the refractive laser beam shaping system, the dark hollow femtosecond pulse beam shaping technique with a phase-only liquid crystal spatial light modulator (LC-SLM) is demonstrated. The phase distribution of the LC-SLM is derived by the energy conservation and constant optical path principle. The effects of the shaping system on the temporal properties, including spectral phase distribution and bandwidth of the femtosecond pulse, are analyzed in detail. Experimental results show that the hollow intensity distribution of the output pulsed beam can be maintained much at more than 1200 mm. The spectral phase of the pulse is changed, and the pulse width is expanded from 199 to 230 fs, which is caused by the spatial-temporal coupling effect. The coupling effect mainly depends on the phase-only LC-SLM itself, not on its loaded phase distribution. The experimental results indicate that the proposed shaping setup can generate a dark hollow femtosecond pulsed beam effectively, because the temporal Gaussian waveform is unchanged.

Impact of Expressing Cells on Glycosylation and Glycan of the SARS-CoV-2 Spike Glycoprotein.

The spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the first point of contact for the virus to recognize and bind to host receptors, is the focus of biomedical research seeking to effectively prevent and treat coronavirus disease (COVID-19). The mass production of spike glycoproteins is usually carried out in different cell systems. Studies have been shown that different expression cell systems alter protein glycosylation of hemagglutinin and neuraminidase in the influenza virus. However, it is not clear whether the cellular system affects the spike protein glycosylation. In this work, we investigated the effect of an expression system on the glycosylation of the spike glycoprotein and its receptor-binding domain. We found that there are significant differences in the glycosylation and glycans attached at each glycosite of the spike glycoprotein obtained from different expression cells. Since glycosylation at the binding site and adjacent amino acids affects the interaction between the spike glycoprotein and the host cell receptor, we recognize that caution should be taken when selecting an expression system to develop inhibitors, antibodies, and vaccines.