Comparative proteomic analysis of seminal plasma exosomes in buffalo with high and low sperm motility.

BACKGROUND: Exosomes are nanosized membranous vesicles secreted by various types of cells, which facilitate intercellular communication by transporting bioactive compounds. Exosomes are abundant in biological fluids including semen, and their protein composition and the potential of seminal plasma exosomes (SPEs) as fertility biomarkers were elucidated in humans, however, little information is available regarding buffalo (Bubalus bubalis). Here, we examined protein correlation between spermatozoa, seminal plasma (SP), and SPEs, and we compared and analyzed protein differences between high-motility (H-motility) and low-motility (L-motility) SPEs in buffalo. RESULTS: SPEs were concentrated and purified by ultracentrifugation combined with sucrose density gradient centrifugation, followed by verification using western blotting, nanoparticle tracking analysis, and transmission electron microscopy. Protein composition in spermatozoa, SP and SPEs, and protein difference in H- and L-motility SPEs were identified by LC-MS/MS proteomic analysis and were functionally analyzed through comprehensive bioinformatics. Many SPEs proteins originated from spermatozoa and SP, and nearly one third were also present in spermatozoa and SP. A series of proteins associated with reproductive processes including sperm capacitation, spermatid differentiation, fertilization, sperm-egg recognition, membrane fusion, and acrosome reaction were integrated in a functional network. Comparative proteomic analyses showed 119 down-regulated and 41 up-regulated proteins in L-motility SPEs, compared with H-motility SPEs. Gene Ontology (GO) enrichment of differentially expressed proteins (DEPs) showed that most differential proteins were located in sperm and vesicles, with activities of hydrolase and metalloproteinase, and were involved in sperm-egg recognition, fertilization, single fertilization, and sperm-zona pellucida binding processes, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differential proteins were mainly involved in the PPRP signaling pathway, calcium signaling pathway, and cAMP signaling pathway, among others. Furthermore, 6 proteins associated with reproduction were validated by parallel reaction monitoring analysis. CONCLUSION: This study provides a comprehensive description of the seminal plasma exosome proteome and may be of use for further screening of biomarkers associated with male infertility.

An Atypical Incontinentia Pigmenti Female with Persistent Mucocutaneous Hyperinflammation and Immunodeficiency Caused by a Novel Germline IKBKG Missense Mutation.

While most missense mutations of the IKBKG gene typically result in Ectodermal Dysplasia with Immunodeficiency, there have been rare reported instances of missense mutations of the IKBKG gene causing both Incontinentia Pigmenti (IP) and immunodeficiency in female patients. In this study, we described an atypical IP case in a 19-year-old girl, characterized by hyperpigmented and verrucous skin areas over the entire body. Remarkably, she experienced recurrent red papules whenever she had a feverish upper respiratory tract infection. Immunohistochemical staining unveiled a substantial accumulation of CD68+ macrophages alongside the TNF-α positive cells in the dermis tissue of new pustules, with increased apoptotic basal keratinocytes in the epidermis tissue of these lesions. Starting from the age of 8 years old, the patient suffered from severe and sustained chronic respiratory mucous membrane scar hyperplasia and occluded subglottic lumen. In addition to elevated erythrocyte sedimentation rate values, inflammatory cells were observed in the pathologic lesions of endobronchial biopsies and Bronchoalveolar Lavage Fluid (BALF) smear. Further histological analysis revealed a destructive bronchus epithelium integrity with extensive necrosis. Simultaneously, the patient experienced recurrent incomplete intestinal obstructions and lips contracture. The patient's BALF sample displayed an augmented profile of proinflammatory cytokines and chemokines, suggesting a potential link to systemic hyperinflammation, possibly underlying the pathogenic injuries affecting the subglottic, respiratory, and digestive systems. Furthermore, the patient presented with recurrent pneumonias and multiple warts accompanied by a T+BlowNKlow immunophenotype. Next generation sequencing showed that the patient carried a novel de novo germline heterozygous missense mutation in the IKBKG gene (c. 821T>C, p. L274P), located in the highly conserved CC2 domain. TA-cloning sequencing of patient's cDNA yielded 30 mutant transcripts out of 44 clones. In silico analysis indicated that the hydrogen bond present between Ala270 and Leu274 in the wild-type NEMO was disrupted by the Leu274Pro mutation. However, this mutation did not affect NEMO expression in peripheral blood mononuclear cells (PBMCs). Moreover, patient PBMCs exhibited significantly impaired TNF-α production following Lipopolysaccharide (LPS) stimulation. X-chromosome inactivation in T cells and neutrophils were not severely skewed. Reduced levels of IκBα phosphorylation and degradation in patient's PBMCs were observed. The NF-κB luciferase reporter assay conducted using IKBKG-deficient HEK293T cells revealed a significant reduction in NF-kB activity upon LPS stimulation. These findings adds to the ever-growing knowledge on female IP that might contribute to the better understanding of this challenging disorder.

Antibacterial Activity Comparison of Three Metal Oxide Nanoparticles and their Dissolved Metal Ions.

The potential ecotoxicity of three metal-oxide nanoparticles (NPs) toward Escherichia coli (E. coli) was investigated, including titanium dioxide (TiO2), copper oxide (CuO), and zinc oxide (ZnO). The true particle sizes of NPs in medium were significantly larger than the advertised sizes. Bacterial toxicity tests showed that the three NPs were harmful to varying degrees. The toxicity of CuO toward E. coli increased with the increasing concentration of CuO. The toxicity of ZnO and TiO2 toward E. coli was highest at NP concentration of 5 and 20 mg/L, respectively, but decreased when the NP concentration was higher, which is closely related with the nanoparticle sizes. Ion toxicity further demonstrated that dissolved metal ions were also responsible for the toxicity of CuO and ZnO. These results highlight the need for caution during the use and disposal of such manufactured nanomaterials to prevent unintended environmental impacts.

[Spectroscopic methods applied to component determination and species identification for coffee].

Spectroscopic analysis was applied to the determination of the nutrient quality of ground, instant and chicory coffees. By using inductively coupled plasma atomic emission spectrometry (ICP-ES), nine mineral elements were determined in solid coffee samples. Caffeine was determined by ultraviolet (UV) spectrometry and organic matter was investigated by Fourier transform infrared (FTIR) spectroscopy. Oxidation-reduction titration was utilized for measuring the oxalate. The differences between ground coffee and instant coffee was identified on the basis of the contents of caffeine, oxalate and mineral elements. Experimental evidence showed that, caffeine in instant coffee was 2-3 times higher than in ground coffee. Oxalate in instant coffee was significantly higher in ground coffee. Mineral elements of Mg, P and Zn in ground coffee is lower than in instant coffee, while Cu is several times higher. The mineral content in chicory coffee is overall lower than the instant coffee. In addition, we determined the content of Ti for different types of coffees, and simultaneously detected the elements of Cu, Ti and Zn in chicory coffee. As a fast detection technique, FTIR spectroscopy has the potential of detecting the differences between ground coffee and instant coffee, and is able to verify the presence of caffeine and oxalate.

Optimization and pathway study on destruction of the spent extraction solvent in supercritical water.

Sustainable management of spent extraction solvents (SES) is paramount in the nuclear industry. This study delves into the optimization and oxidation pathways of treating these solvents using supercritical water oxidation (SCWO). Response surface methodology (RSM) has been employed to optimize key operating variables, that is, temperature, residence time and oxidant concentration, producing a highly accurate quadratic polynomial model. The results showed that the total organic carbon (TOC) removal could reach up to 99.25% under 549 °C, 67.7 s and with an oxidation coefficient of 274.3%. Product analysis of the effluent via GC-MS/FTIR/GC revealed the pivotal role of ketones and aldehydes as major intermediates. This study proposes potential chemical pathways for the destruction of these solvents, providing invaluable insights for process intensification. In conclusion, this study underscores the potential of SCWO as an efficient and sustainable solution for disposing of SES in the nuclear industry.

A novel data fusion based intelligent identification approach for working cycle stages of hydraulic excavators.

Accurately identifying the stage of the excavator working cycle is the prerequisite to achieve the staged energy-saving control. However, current identification methods often overlook the influence of hydraulic system latency on identification results and depend on a single model, resulting in poor generalization performance of the identification approaches. Moreover, expert calibration system remains a necessary factor for improving identification accuracy. Aiming at these issues, a hybrid multi-scale feature extractor and a decision-level data fusion classifier approach (HMSFE-DFC) is proposed to identify the working cycle stages of excavator. The input signal employs mixed signals from the main pump pressure and the control current of the proportional solenoid valve to reduce the response delay caused by the single main pump pressure signal. A hybrid multi-scale feature extractor is constructed using a convolutional neural network temporal self-attention feature extraction mechanism and one-dimensional ResNet-50 architecture to extract multiscale features. To prevent overfitting, a decision-level data fusion classifier is used to fuse the decisions information of numerous classifiers. The accuracy of stage identification for 10 consecutive working cycles reaches 95.21%, which verifies its effectiveness.

Characterization of the Complete Mitochondrial Genome of Schizothorax kozlovi (Cypriniformes, Cyprinidae, Schizothorax) and Insights into the Phylogenetic Relationships of Schizothorax.

Schizothorax kozlovi is an endemic and vulnerable fish species found in the upper Yangtze River in China. Over the past few years, the population resources of S. kozlovi have been nearly completely depleted owing to multiple contributing threats. While the complete mitochondrial genomes serve as important molecular markers for phylogenetic and genetic studies, the mitochondrial genome of S. kozlovi has still received little attention. In this study, we analyzed the characterization of the mitochondrial genome of S. kozlovi and investigated the phylogenetic relationships of Schizothorax. The complete mitochondrial genome of S. kozlovi was 16,585 bp in length, which contained thirty-seven genes (thirteen protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), twenty-two transfer RNA genes (tRNAs)) and two non-coding regions for the origin of light strand (OL) and the control region (CR). There were nine overlapping regions and seventeen intergenic spacers regions in the mitochondrial genome. The genome also showed a bias towards A + T content (55.01%) and had a positive AT-skew (0.08) and a negative GC-skew (-0.20). All the PCGs employed the ATG or GTG as the start codon and TAA, TAG, or single T as the stop codon. Additionally, all of the tRNAs displayed a typical cloverleaf secondary structure, except trnS1 which lacked the D arm. The phylogenetic analysis, based on the maximum likelihood (ML) and Bayesian inference (BI) methods, revealed that the topologies of the phylogenetic tree divided the Schizothorax into four clades and did not support the classification of Schizothorax based on morphology. The phylogenetic status of S. kozlovi was closely related to that of S. chongi. The present study provides valuable genomic information for S. kozlovi and new insights in phylogenetic relationships of Schizothorax. These data could also offer fundamental references and guidelines for the management and conservation of S. kozlovi and other species of Schizothorax.

Knowledge, attitudes, and practices regarding cardiovascular disease prevention among middle school students in China: a cross-sectional study.

Background: The prevalence of cardiovascular disease (CVD) is rapidly increasing globally. With a concerning increase among adolescents due to unhealthy habits, obesity, and hypertension, understanding the current status of knowledge, attitudes, and practices (KAP) related to CVD prevention among middle school students is crucial for developing effective school-based health programs to prevent CVD. Methods: The analytic cross-sectional survey is used in questionnaires to assess KAP related to CVD prevention among middle school students (N = 17,731) from 50 schools across 16 provinces in China in June-July 2023. The pass rate of KAP scores is categorized as good and poor. Independent predictors of good KAP of CVD prevention are ascertained using a binary logistic regression model. Results: The study surveyed 8,118 (45.78%) junior high school students and 9,613 (54.22%) high school students. The overall mean [standard deviation (SD)] for the knowledge, attitude, and practice scores were 26.88 (8.12), 53.53 (7.22), and 39.80 (5.96), respectively. The knowledge scores had the lowest pass rate at 56.89%. Only 6.83% of the students know "the definition of blood pressure in adolescents." Attitudes toward health were positive, though the attitude regarding "the danger of prolonged sedentary to cardiovascular health" scored lowest at 73.55%. The practice section had a pass rate of 89.30%; 40.27% of students reported that they spend more than an hour a day on screens. Only one-third of the students would go to bed before 12 o'clock. In univariate analysis, junior high school and high school students differed significantly in knowledge and practice (p < 0.001), but attitude did not differ significantly (p = 0.103). Conclusion: The majority of students lack sufficient knowledge about CVD. It is also found that socioeconomic background, family environment, and educational levels have an impact on cardiovascular health behaviors among students. Strengthening health education involving students, parents, teachers, and communities is essential to promote health knowledge and practices among adolescents.

High-Temperature-Resistant, Clean, and Environmental-Friendly Fracturing Fluid System and Performance Evaluation of Tight Sandstone.

Hydraulic fracturing, as an oil-water well stimulation and injection technology, is particularly important in the production and stimulation of low-permeability oil and gas fields, and the performance of the fracturing fluid directly affects the success of the fracturing operation. Compared with traditional water-based fracturing fluids, clean fracturing fluids have the advantages of strong sand-carrying ability and easy gel breaking with no residue. Aiming at the problem of poor temperature resistance and shear resistance of the clean fracturing fluid, based on previous research, this paper selects a high-temperature-resistant clean fracturing fluid system and evaluates the performance of the system. The research results show that the system has better rheological properties, better sand-carrying performance, shorter gel-breaking time, and less damage to the reservoir.

Endothelial Cells Potentially Participate in the Metastasis of Triple-Negative Breast Cancer.

Inhibition of triple-negative breast cancer metastasis has long been a challenge, mainly due to the difficulty in identifying factors that contribute to this process. In this study, freshly isolated triple-negative breast cancer biopsied cells obtained from consenting patients were subjected to flow cytometry and bioinformatic analysis to identify three endothelial cell subclusters: EC (ATP1B3), EC (HSPA1B), and EC (KRT7) in the tumor microenvironment. These endothelial cell subclusters exhibited distinguishing biological features. Based on differentially expressed genes derived from the subclusters, gene set enrichment analysis showed that EC (ATP1B3) and EC (HSPA1B) contribute to the process of metastasis, for example, in fibrosarcoma and anaplastic carcinoma. In this study, we identified the heterogeneity of endothelial cells in the human breast cancer and have provided insights into its role in metastasis.

Induction chemotherapy regimen of docetaxel plus cisplatin versus docetaxel, cisplatin plus fluorouracil followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Preliminary results of an open-label, noninferiority, multicentre, randomised, controlled phase 3 trial.

Background: Induction chemotherapy regimens of docetaxel and cisplatin plus fluorouracil (TPF) are currently clinically used for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but have well-known side effects, such as myelosuppression and diarrhea. A docetaxel plus cisplatin (TP) regimen was developed to decrease the toxic effects induced by fluorouracil. In this trial, we assessed whether the TP induction chemotherapy regimen was noninferior to the TPF regimen. Methods: We performed an open-label, noninferiority, phase 3, multicentre, randomised, controlled trial at six centres in China. Eligible patients with NPC (stage III-IVA (excluding T3-4N0), Karnofsky's Performance Scoring ≥70) were randomly assigned (1:1) to receive either TP (docetaxel (75 mg per square meter, d1, intravenous infusion) and cisplatin (75 mg per square meter of body-surface area, d1, intravenous infusion)) or TPF (docetaxel (60 mg per square meter, d1, intravenous infusion) plus cisplatin (60 mg per square meter, d1, intravenous infusion) and 5-fluorouracil (600 mg per square meter, d1-d5, intravenous 120-hour infusion)) administered every 3 weeks for 3 cycles followed by concurrent chemoradiotherapy. The primary endpoint was failure-free survival at 2 years. Secondary endpoints included overall survival, safety, and treatment compliance. The trial was stopped early because of strong evidence for noninferiority (margin was -10%) of TP in failure-free survival. Efficacy analyses were performed in both the intention-to-treat and per-protocol trial populations and we included the patients who started treatment in each group for the safety analysis. The study was registered with chictr.org.cn, ChiCTR1800016337. Findings: Between June 1, 2018 and October 31, 2021, we randomly assigned 361 patients to the TP (n = 181) or TPF (n = 180) induction chemotherapy group. The 2-year failure-free survival was 91·3% (95% CI 86·2-96·4) in the TP group and 82·4% (84·8-88·9) in the TPF group (P = 0·029). Patients in the TPF group had a higher frequency of grade 1 or 2 neutropenia (53 (30·0%) vs. 28 (15·7%); P = 0·0010), grade 1 or 2 diarrhea (20 (11·3%) vs. 9 (5·1%); P = 0·032), and grade 3 or 4 neutropenia (43 (24·3%) vs. 25 (14·0%); P = 0·014) in the induction chemotherapy period. There was no treatment-related death. Interpretation: The preliminary results revealed that TP induction chemotherapy regimen was found to be clearly non-inferior compared to the TPF regimen in failure-free survival, with a lower frequency of neutropenia, anaemia and diarrhoea. The more convenient and beneficial survival regimen of the TP regimen should be recommended in patients with LA-NPC. Funding: This study was supported by grants from the Natural Science Foundation of Guangdong Province, China [grant number 2021A1515011182], Natural Science Foundation of Guangdong Province, China [grant number 2022A1515012272], National Natural Science Foundation of China [grant number 82072029] and National Natural Science Foundation of China [grant number 81903037].

Molecular imaging of vulnerable plaques in rabbits using contrast-enhanced ultrasound targeting to vascular endothelial growth factor receptor-2.

PURPOSE: Increased neovascularization has been identified as a feature of atherosclerotic plaque vulnerability and can be traced by microbubble ultrasound contrast agents (UCA). We investigated the relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR-2) targeted UCA and VEGFR-2 expression in a vulnerable plaque model in rabbits. METHODS: Microbubbles targeting to VEGFR-2 were prepared by conjugation of biotinylated microbubbles with biotinylated VEGFR-2 antibody via streptavidin. Vulnerability was created by delivering recombinant p53 adenovirus to atherosclerotic plaques obtained in abdominal aorta by a high cholesterol diet and balloon endothelial injury. Twelve week later, the average video intensity of pre- and postcontrast ultrasound images was measured. VEGFR-2 expression and vascular density were quantified by immunohistochemical staining. RESULTS: Retention of targeted UCA in plaques was higher than that of nontargeted UCA (144 ± 18 dB versus 107 ± 9 dB; Z= -3.984, p = 0.000). VEGFR-2 expression was correlated with video intensity of targeted (r(2) = 0.78, p = 0.001), but not of nontargeted, UCA (r(2) = 0.17, p ≥ 0.05). CONCLUSIONS: The magnitude of the sonographic signal from retained VEGFR-2 targeted UCA correlates with VEGFR-2 expression. These results validate the use of targeted UCA for sonographic imaging of vulnerable abdominal artery plaques in rabbits.

Electrochemical treatment of residual ammonia nitrogen in biologically pretreated coking wastewater with three-dimensional electrodes.

The electrochemical oxidation of the residual ammonia nitrogen contained in biologically pretreated coking wastewater using three-dimensional electrode system was studied. The results show the Ti/RuO2/IrO2 anode plates and the coke have good surface characteristics for the purpose of this study. In addition, studies also show that the three-dimensional electrode system should be able to give a satisfied solution to the residual bio-refractory ammonia nitrogen in biologically pretreated coking wastewater in comparison to conventional two-dimensional electrodes. At coke size of 10-20 mesh, electrode distance of 1.0 cm and current density of 4.5 mA/cm2, the residual ammonia nitrogen in the three-dimensional electrode system was almost completely removed in 60 min.

Classification and immune invasion analysis of breast cancer based on m6A genes.

BACKGROUND: Breast cancer (BRCA) shows genetic, epigenetic, and phenotypic diversity. Methylation of N6-methyladenosine (m6A) affects the occurrence, development, and therapeutic efficacy of BRCA. However, the characteristics and prognostic value of m6A in BRCA remain unclear. We aimed to classify and construct a scoring system for the m6A regulatory gene in BRCA, and to explore its potential mechanisms. METHODS: In this study, we selected 23 m6A regulatory genes and analyzed their genetic variation in BRCA, including copy number variation (CNV) data, expression differences, mutations, gene types, and correlations between genes. Survival curves were drawn by the Kaplan-Meier method, and a log-rank P<0.05 was considered statistically significant. The partitioning around medoids (PAM) algorithm was used for molecular subtype analysis of m6A, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to quantify the relative infiltration levels of various immune cell subgroups, and a scoring system was built based on principal component analysis (PCA). RESULTS: In BRCA, m6A regulatory gene mutation frequency is not high, while that of CNV mutation is high, which is related to gene expression and closely related to prognosis. In this study, we identified 3 different m6A subtypes, which are closely related to the level of immune cell infiltration. We further constructed an m6A score system, in which lower scores were correlated with low tumor mutation burden (TMB), later clinical staging, programmed cell death 1 ligand 1 (PD-L1) expression, and triple-negative breast cancer (TNBC). CONCLUSIONS: This study highlights the diversity and complexity of the role of m6A in BRCA. The classification of BRCA based on the m6A regulatory gene can help us understand the characteristics of BRCA and help develop individualized immunotherapy regimens.

The inhibitor effect of RKIP on inflammasome activation and inflammasome-dependent diseases.

Aberrant inflammasome activation contributes to the pathogenesis of various human diseases, including atherosclerosis, gout, and metabolic disorders. Elucidation of the underlying mechanism involved in the negative regulation of the inflammasome is important for developing new therapeutic targets for these diseases. Here, we showed that Raf kinase inhibitor protein (RKIP) negatively regulates the activation of the NLRP1, NLRP3, and NLRC4 inflammasomes. RKIP deficiency enhanced caspase-1 activation and IL-1ß secretion via NLRP1, NLRP3, and NLRC4 inflammasome activation in primary macrophages. The overexpression of RKIP in THP-1 cells inhibited NLRP1, NLRP3, and NLRC4 inflammasome activation. RKIP-deficient mice showed increased sensitivity to Alum-induced peritonitis and Salmonella typhimurium-induced inflammation, indicating that RKIP inhibits NLRP3 and NLRC4 inflammasome activation in vivo. Mechanistically, RKIP directly binds to apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and competes with NLRP1, NLRP3, or NLRC4 to interact with ASC, thus interrupting inflammasome assembly and activation. The depletion of RKIP aggravated inflammasome-related diseases such as monosodium urate (MSU)-induced gouty arthritis and high-fat diet (HFD)-induced metabolic disorders. Furthermore, the expression of RKIP was substantially downregulated in patients with gouty arthritis or type 2 diabetes (T2D) compared to healthy controls. Collectively, our findings suggest that RKIP negatively regulates NLRP1, NLRP3, and NLRC4 inflammasome activation and is a potential therapeutic target for the treatment of inflammasome-related diseases.

Stk24 protects against obesity-associated metabolic disorders by disrupting the NLRP3 inflammasome.

Adipose tissue macrophages (ATMs) regulate the occurrence of obesity and its related diseases. Here, we found that serine/threonine protein kinase 24 (Stk24) expression is downregulated significantly in ATMs in obese subjects or obese subjects with type 2 diabetes and mice fed a high-fat diet (HFD). We further identified that glucolipotoxicity downregulated Stk24 expression in ATMs. Stk24-deficient mice develop severe HFD-induced metabolic disorders and insulin insensitivity. Mechanistically, Stk24 intervenes in NLRP3 inflammasome assembly in ATMs by associating directly with NLRP3, decreasing interleukin-1ß (IL-1ß) secretion. Accordingly, Stk24 deficiency in the hematopoietic system promotes NLRP3 inflammasome activation, which contributes to exacerbation of metabolic disorders. Intriguingly, Stk24 expression correlates negatively with body mass index (BMI) and the levels of glucose, cholesterol, triglycerides, and low-density lipoprotein in human subjects. These findings provide insights into the function and clinical implications of Stk24 in obesity-mediated metabolic disorders.

The immune-related gene CD52 is a favorable biomarker for breast cancer prognosis.

BACKGROUND: An increasing number of studies have demonstrated a role for the tumor microenvironment in tumorigenesis, disease progression, and therapeutic response. This present study aimed to screen the significant immune-related genes and their possible role in the prognosis of breast cancer (BRCA). METHODS: The transcriptome data and clinical data of breast cancer were collected from The Cancer Genome Atlas (TCGA), and the immune scores and stromal scores were calculated by ESTIMATE algorithm. The differentially expressed genes were screened base on immune and stromal scores (high score vs. low score), than the intersected genes were used for subsequent functional enrichment analysis and protein-protein interaction (PPI) analysis. Furthermore, the key gene was identified by the intersection of the hub genes of PPI network and the prognostic genes of breast cancer. Finally, we explored the infiltration of immune cells of BRCA base on the CIBERSORT algorithm, and analysis the relationship between key gene and immune cells. RESULTS: High levels of CD52 expression were detected in the early stages of breast cancer and were associated with favorable prognosis. Overexpression of CD52 led to higher infiltrations of M1 macrophages, monocytes, T follicular helper cells, and resting memory CD4 T cells. Downregulation of CD52 resulted in high infiltrations of M2 macrophages. Therefore, high expression of CD52 may negatively regulate the infiltration of M2 macrophages but accelerate the infiltration of anti-cancer immune cells, and thus, high expression of CD52 may have a protective effect in breast cancer patients. CONCLUSIONS: CD52 can increase the infiltration of anti-cancer immune cells but inhibit the infiltration of M2 macrophages, thereby improving the prognosis of breast cancer patients.

Mass spectrometric-based stable isotopic 2-aminobenzoic acid glycan mapping for rapid glycan screening of biotherapeutics.

Fast, sensitive, robust methods for "high-level" glycan screening are necessary during various stages of a biotherapeutic product's lifecycle, including clone selection, process changes, and quality control for lot release testing. Traditional glycan screening involves chromatographic or electrophoretic separation-based methods, and, although reproducible, these methods can be time-consuming. Even ultrahigh-performance chromatographic and microfluidic integrated LC/MS systems, which work on the tens of minute time scale, become lengthy when hundreds of samples are to be analyzed. Comparatively, a direct infusion mass spectrometry (MS)-based glycan screening method acquires data on a millisecond time scale, exhibits exquisite sensitivity and reproducibility, and is amenable to automated peak annotation. In addition, characterization of glycan species via sequential mass spectrometry can be performed simultaneously. Here, we demonstrate a quantitative high-throughput MS-based mapping approach using stable isotope 2-aminobenzoic acid (2-AA) for rapid "high-level" glycan screening.

Novel indoline-1- or 3,4-dihydroquinoline-1(2H)-substituted carbothiohydrazides as TPO receptor agonists.

Synthesis and evaluation of novel series of indoline-1- or 3,4-dihydroquinoline-1(2H)-substituted carbothiohydrazide or carbohydrazide based small molecule compounds as thrombopoietin (TPO) receptor agonists are reported. Members of these compounds have been identified as full agonists of human c-mpl in BaF3/TPOR cell line. Indoline-1-carbohydrazide 9b exhibited reasonable pharmacokinetic profile.

The burden of respiratory syncytial virus associated with acute lower respiratory tract infections in Chinese children: a meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV), which is associated with acute lower respiratory tract infection (ALRTI), is highly common among children. The burden of RSV varies between countries. In China, the actual burden remains unclear. Thus, this meta-analysis aimed to quantify the positive rate of ALRTI-related RSV infections among Chinese children in recent years. METHODS: The PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese BioMedical (CBM) databases were searched to identify relevant cross-sectional studies published between January 1, 2015 and December 31, 2018. Subsequently, a meta-analysis was performed using R software. RESULTS: A total of 18 studies involving 66,799 ALRTI cases were finally included in the meta-analysis. Among those ALRTIs cases, the overall positive rate of RSV infection was 16.0% (95% CI: 12.9-19.6%). The rate was significantly higher in children <3 years (19.5%, 95% CI 13.3-27.6%) compared to those ≥3 years (5.6%, 95% CI: 2.3-13.2%; P<0.01). Moreover, stratified analysis revealed that RSV infection was most frequent in children <6 months (31.1%, 95% CI: 21.0-43.5%). The positive detection rate of RSV infection was significantly associated with season (P<0.01), with winter having the highest detection rate (29.0%, 95% CI: 21.3-38.2%), followed by autumn (20.9%, 95% CI: 10.5-37.3%), and summer having the lowest rate (6.4%, 95% CI: 2.3-16.9%). The rate of RSV infection was highest and lowest in November (49.4%, 95% CI: 29.0-70.0%) and June (1.3%, 95% CI: 0.6-2.8%), respectively. When stratified according to geographical region, RSV infections peaked in winter (South: 24.8%, 95% CI: 12.9-42.3%; North: 36.3%, 95% CI: 30.8-42.1%), followed by autumn (South: 13.9%, 95% CI: 6.5-27.4%; North: 32.7%, 95% CI: 20.2-48.3%). CONCLUSIONS: In conclusion, our meta-analysis showed that among Chinese children with ALRTI, 16.0% had RSV infection. RSV infection frequently occurred in children under the age of 3 years, especially in those under 6 months. The rate of RSV infections was highest in winter, followed by autumn.