Epidemiological behaviour and interventions of malaria in Niger, 2010-2019: a time-series analysis of national surveillance data.

BACKGROUND: Malaria remains a significant public health concern in Niger, with the number of cases increasing from 592,334 in 2000 to 3,138,696 in 2010. In response, a concerted campaign against the disease has been initiated. However, the implementation of these malaria interventions and their association with epidemiological behaviour remains unclear. METHODS: A time-series study was conducted in Niger from 2010 to 2019. Multiple data sources concerning malaria were integrated, encompassing national surveillance data, Statistic Yearbook, targeted malaria control interventions, and meteorological data. Incidence rate, mortality rate, and case fatality ratio (CFR) by different regions and age groups were analysed. Joinpoint regression models were used to estimate annual changes in malaria. The changes in coverage of malaria interventions were evaluated. RESULTS: Between 2010 to 2019, the incidence rate of malaria decreased from 249.43 to 187.00 cases per 1,000 population in Niger. Niamey had a high annual mean incidence rate and the lowest CFR, while Agadez was on the contrary. Joinpoint regression analysis revealed a declining trend in malaria incidence for all age groups except the 10-24 years group, and the mortality rate and the CFR initially decreased followed by an increase in all age groups. Niger has implemented a series of malaria interventions, with the major ones being scaled up to larger populations during the study period. CONCLUSIONS: The scale-up of multi-interventions in Niger has significantly reduced malaria incidence, but the rise in mortality rate and CFR addresses the challenges in malaria control and elimination. Malaria endemic countries should enhance surveillance of malaria cases and drug resistance in Plasmodium, improve diagnosis and treatment, expand the population coverage of insecticide-treated bed nets and seasonal malaria chemoprevention, and strengthen the management of severe malaria cases.

Comorbidity increases the risk of pulmonary tuberculosis: a nested case-control study using multi-source big data.

BACKGROUND: Some medical conditions may increase the risk of developing pulmonary tuberculosis (PTB); however, no systematic study on PTB-associated comorbidities and comorbidity clusters has been undertaken. METHODS: A nested case-control study was conducted from 2013 to 2017 using multi-source big data. We defined cases as patients with incident PTB, and we matched each case with four event-free controls using propensity score matching (PSM). Comorbidities diagnosed prior to PTB were defined with the International Classification of Diseases-10 (ICD-10). The longitudinal relationships between multimorbidity burden and PTB were analyzed using a generalized estimating equation. The associations between PTB and 30 comorbidities were examined using conditional logistic regression, and the comorbidity clusters were identified using network analysis. RESULTS: A total of 4265 cases and 17,060 controls were enrolled during the study period. A total of 849 (19.91%) cases and 1141 (6.69%) controls were multimorbid before the index date. Having 1, 2, and ≥ 3 comorbidities was associated with an increased risk of PTB (aOR 2.85-5.16). Fourteen out of thirty comorbidities were significantly associated with PTB (aOR 1.28-7.27), and the associations differed by sex and age. Network analysis identified three major clusters, mainly in the respiratory, circulatory, and endocrine/metabolic systems, in PTB cases. CONCLUSIONS: Certain comorbidities involving multiple systems may significantly increase the risk of PTB. Enhanced awareness and surveillance of comorbidity are warranted to ensure early prevention and timely control of PTB.

Growth of Vertical Graphene Sheets on Silicon Nanoparticles Well-Dispersed on Graphite Particles for High-Performance Lithium-Ion Battery Anode.

With rapidly increasing demand for high energy density, silicon (Si) is greatly expected to play an important role as the anode material of lithium-ion batteries (LIBs) due to its high specific capacity. However, large volume expansion for silicon during the charging process is still a serious problem influencing its cycling stability. Here, a Si/C composite of vertical graphene sheets/silicon/carbon/graphite (VGSs@Si/C/G) is reported to address the electrochemical stability issues of Si/graphite anodes, which is prepared by adhering Si nanoparticles on graphite particles with chitosan and then in situ growing VGSs by thermal chemical vapor deposition. As a promising anode material, due to the buffering effect of VGSs and tight bonding between Si and graphite particles, the composite delivers a high reversible capacity of 782.2 mAh g-1 after 1000 cycles with an initial coulombic efficiency of 87.2%. Furthermore, the VGSs@Si/C/G shows a diffusion coefficient of two orders higher than that without growing the VGSs. The full battery using VGSs@Si/C/G anode and LiNi0.8 Co0.1 Mn0.1 O2 cathode achieves a high gravimetric energy density of 343.6 Wh kg-1 , a high capacity retention of 91.5% after 500 cycles and an excellent average CE of 99.9%.

Detection approach for GEO space objects with a wide-field optical telescope array.

In 2020, Changchun Observatory developed a 280 mm wide-field optical telescope array to improve surveillance of space debris in the geosynchronous belt. There are many advantages including a wide field of view, the ability to observe a large area of sky and high reliability. However, the wide field of view causes a significant number of background stars to appear in the image when photographing space objects, making it difficult to detect them. This research focuses on the precise detection of GEO space objects from images taken by this telescope array in order to position them in large quantities. Our work further investigates the motion feature of an object, namely that the object can be seen as being in a uniform linear motion for a brief length of time. Based on this feature, the belt can be divided into a number of smaller areas and the telescope array scans each smaller area one at a time from east to west. To detect objects in the subarea, a combination of image differencing with trajectory association is used. The image differencing algorithm is used to remove most stars and screen out suspected objects in the image. Next, the trajectory association algorithm is employed to further filter out the real objects among the suspected ones, and the trajectories attributed to the same object are linked. The feasibility and accuracy of the approach were verified by the experiment results. The accuracy rate of trajectory association exceeds 90% and on average, more than 580 space objects can be detected per observation night. Since the J2000.0 equatorial system can accurately describe the apparent position of an object, the object can be detected by using this coordinate system as opposed to the pixel coordinate system.

Characterization of the natural peptidome of four leeches by integrated proteogenomics and pseudotargeted peptidomics.

Animal-derived drugs are an indispensable part of folk medicine worldwide. However, their chemical constituents are poorly approached, which leads to the low level of the quality standard system of animal-derived drugs and further causes a chaotic market. Natural peptides are ubiquitous throughout the organism, especially in animal-derived drugs. Thus, in this study, we used multi-source leeches, including Hirudo nipponica (HN), Whitmania pigra (WP), Whitmania acranulata (WA), and Poecilobdella manillensis (PM), as a model. A strategy integrating proteogenomics and novel pseudotargeted peptidomics was developed to characterize the natural peptide phenotype and screen for signature peptides of four leech species. First, natural peptides were sequenced against an in-house annotated protein database of closely related species constructed from RNA-seq data from the Sequence Read Archive (SRA) website, which is an open-sourced public archive resource. Second, a novel pseudotargeted peptidomics integrating peptide ion pair extraction and retention time transfer was established to achieve high coverage and quantitative accuracy of the natural peptides and to screen for signature peptides for species authentication. In all, 2323 natural peptides were identified from four leech species whose databases were poorly annotated. The strategy was shown to significantly improve peptide identification. In addition, 36 of 167 differential peptides screened by pseudotargeted proteomics were identified, and about one-third of them came from the leucine-rich repeat domain (LRR) proteins, which are widely distributed in organisms. Furthermore, six signature peptides were screened with good specificity and stability, and four of them were validated by synthetic standards. Finally, a dynamic multiple reaction monitoring (dMRM) method based on these signature peptides was established and revealed that one-half of the commercial samples and all of the Tongxinluo capsules were derived from WP. All in all, the strategy developed in this study was effective for natural peptide characterization and signature peptide screening, which could also be applied to other animal-derived drugs, especially for modelless species that are less studied in protein database annotation.

DNA methylation profile in the whole blood of acute coronary syndrome patients with aspirin resistance.

BACKGROUND: Aspirin resistance (AR) results in major adverse cardiovascular events, and DNA methylation might participate in the regulation of this pathological process. METHODS: In present study, a sum of 35 patients with AR and 35 non-AR (NAR) controls were enrolled. Samples from 5 AR and 5 NAR were evaluated in an 850 BeadChip DNA methylation assay, and another 30 AR versus 30 NAR were evaluated to validate the differentially methylated CpG loci (DML). Then, qRT-PCR was used to investigate the target mRNA expression of genes at CpG loci. Finally, Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to reveal the enriched pathways. RESULTS: The AR and NAR groups displayed significant differences in DNA methylation at 7707 positions, with 270 hypermethylated sites (e.g., cg09555818 located in APOC2) and 7437 sites hypomethylated sites (e.g., cg26828689 located in SLC12A5). Six DML were validated by pyrosequencing, and it was confirmed that DNA methylation (cg16391727, cg21008208, cg21293749, and cg13945576) was related to the increasing risk of AR. The relative mRNA expression of the ROR1 gene was also associated with AR (p = 0.007), suggesting that the change of cg21293749 in DNA methylation might lead to differential ROR1 mRNA expression, ultimately resulting in AR. Furthermore, the identified differentially methylated sites were associated with the molecular pathways such as circadian rhythms and insulin secretion. CONCLUSION: Hence, the distinct DNA methylation might play a vital role in the biological regulation of AR through the pathways such as circadian rhythms.

Analysis of the Impact of Atmospheric Models on the Orbit Prediction of Space Debris.

Atmospheric drag is an important influencing factor in precise orbit determination and the prediction of low-orbit space debris. It has received widespread attention. Currently, calculating atmospheric drag mainly relies on different atmospheric density models. This experiment was designed to explore the impact of different atmospheric density models on the orbit prediction of space debris. In the experiment, satellite laser ranging data published by the ILRS (International Laser Ranging Service) were used as the basis for the precise orbit determination for space debris. The prediction error of space debris orbits at different orbital heights using different atmospheric density models was used as a criterion to evaluate the impact of atmospheric density models on the determination of space-target orbits. Eight atmospheric density models, DTM78, DTM94, DTM2000, J71, RJ71, JB2006, MSIS86, and NRLMSISE00, were compared in the experiment. The experimental results indicated that the DTM2000 atmospheric density model is best for determining and predicting the orbits of LEO (low-Earth-orbit) targets.

Ballistic Coefficient Calculation Based on Optical Angle Measurements of Space Debris.

Atmospheric drag is an important factor affecting orbit determination and prediction of low-orbit space debris. To obtain accurate ballistic coefficients of space debris, we propose a calculation method based on measured optical angles. Angle measurements of space debris with a perigee height below 1400 km acquired from a photoelectric array were used for orbit determination. Perturbation equations of atmospheric drag were used to calculate the semi-major-axis variation. The ballistic coefficients of space debris were estimated and compared with those published by the North American Aerospace Defense Command in terms of orbit prediction error. The 48 h orbit prediction error of the ballistic coefficients obtained from the proposed method is reduced by 18.65% compared with the published error. Hence, our method seems suitable for calculating space debris ballistic coefficients and supporting related practical applications.

Glycolysis Reprogramming in Idiopathic Pulmonary Fibrosis: Unveiling the Mystery of Lactate in the Lung.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by excessive deposition of fibrotic connective tissue in the lungs. Emerging evidence suggests that metabolic alterations, particularly glycolysis reprogramming, play a crucial role in the pathogenesis of IPF. Lactate, once considered a metabolic waste product, is now recognized as a signaling molecule involved in various cellular processes. In the context of IPF, lactate has been shown to promote fibroblast activation, myofibroblast differentiation, and extracellular matrix remodeling. Furthermore, lactate can modulate immune responses and contribute to the pro-inflammatory microenvironment observed in IPF. In addition, lactate has been implicated in the crosstalk between different cell types involved in IPF; it can influence cell-cell communication, cytokine production, and the activation of profibrotic signaling pathways. This review aims to summarize the current research progress on the role of glycolytic reprogramming and lactate in IPF and its potential implications to clarify the role of lactate in IPF and to provide a reference and direction for future research. In conclusion, elucidating the intricate interplay between lactate metabolism and fibrotic processes may lead to the development of innovative therapeutic strategies for IPF.

Fingerprinting Evaluation and Gut Microbiota Regulation of Polysaccharides from Jujube (Ziziphus jujuba Mill.) Fruit.

Jujube fruit was well-loved and praised by the broad masses due to its delicious taste, abundant nutritional value, and medicinal properties. Few studies reported the quality evaluation and gut microbiota regulation effect of polysaccharides of jujube fruits from different producing areas. In the present study, multi-level fingerprint profiling, including polysaccharides, oligosaccharides, and monosaccharides, was established for the quality evaluation of polysaccharides from jujube fruits. For polysaccharides, the total content in jujube fruits ranged from 1.31% to 2.22%, and the molecular weight distribution (MWD) ranged from 1.14 × 105 to 1.73 × 106 Da. The MWD fingerprint profiling of polysaccharides from eight producing areas was similar, but the profile of infrared spectroscopy (IR) showed differentiation. The characteristic signals were screened and used to establish a discrimination model for the identification of jujube fruits from different areas, and the accuracy of identification reached 100.00%. For oligosaccharides, the main components were galacturonic acid polymers (DP, 2-4), and the profile of oligosaccharides exhibited high similarity. The monosaccharides, GalA, Glc, and Ara, were the primary monosaccharides. Although the fingerprint of monosaccharides was semblable, the composing proportion of monosaccharides revealed significant differences. In addition, the polysaccharides of jujube fruits could regulate the gut microbiota composition and possess potential therapeutic effects on dysentery and nervous system diseases.

Atomic-Scale Laminated Structure of O-Doped WS2 and Carbon Layers with Highly Enhanced Ion Transfer for Fast-Charging Lithium-Ion Batteries.

WS2 anode materials show huge potential for fast-charging lithium-ion batteries (LIBs) due to the naturally good 2D diffusion pathways but suffer from large Li+ diffusion barrier energy and poor intrinsic electrical conductivity. Here, a defect-rich atomic-scale laminated structure of WS2 and C (D-WS2 -C) with O doping and enlarged interlayer distance from 0.62 to 1.06 nm of WS2 is first fabricated, which is assembled into micron-sized spheres to prepare WS2 /C composite microspheres. D-WS2 -C with maximized molecular layer contact area between WS2 and carbon and large interlayer spacing greatly enhances the electrical conductivity of WS2 and reduces Li-ion diffusion energy barrier, confirmed by density functional theory calculations. Besides, the unique D-WS2 -C enables the formation of vast superfine W nanoparticles (1-2 nm) during the conversation reaction, resulting in the construction of a space charge zone on W surface. Based on these characteristics of D-WS2 -C, the prepared WS2 /C composite microspheres show superior fast-charging capability with a high capacity of 647.8 mAh g-1 at 20 C in half cells. For full cells, a high-energy density of 100.9 Wh kg-1 is achieved at a charge time of only 8.5 min at 5 C, representing the best fast-charging performances in WS2 -based anode materials to date.

Super diffraction limit spectral imaging detection and material type identification of distant space objects.

The image information of distant objects shows a diffuse speckle pattern due to diffraction limit, non-uniform scattering, etc., which is difficult to achieve object discrimination. In this study, we have developed a staring spectral video imaging system mounted on a ground-based telescope observation platform to detect the high orbit space objects and gain their spectral images for six groups of GEO targets. The speckle remains basically the same characteristic as the projection structure of the object due to "the balloon inflation phenomenon of near parallel light during long-distance atmospheric transmission" under the premise of considering the bi-directional reflection distribution function (BRDF), Rayleigh scattering theory, and the memory effect. Based on this phenomenon, a mathematical model of remote target scattering spectrum imaging is established where the speckle can be treated as both a global speckle and speckle combination of texture blocks caused by various components of the target. The radial basis function (RBF) neural network is separately used to invert the global speckle and the speckle combination of the texture blocks on account of the typical target material database. The results show that the target materials are of relatively fewer kinds in the global inversion with only including gallium arsenide panel (GaAs) and carbon fiber (CF), for which the highest goodness of curve fitting is only 77.97. An improved algorithm makes their goodness of fit reach 90.29 and 93.33, respectively, in view of one conjecture that the target surface contains unknown materials. The spectral inversion result of the texture blocks shows that the types of materials in each target texture block increase significantly, and that the area ratio of different materials inverted in the block is different from each other. It is further confirmed that the speckle image contains the overall projection structure of distant target and the spectral image projection of each component is relatively fixed, which is the result of the comprehensive action of various mechanisms of ultra-long-haul atmospheric transmission and optical system focusing imaging after BRDF spectral scattering. The spectral image fine inversion is expected to restore the clear structure of the target. This discovery provides important support for the remote imaging and identification of distant and ultra-diffractive targets.

Profile and dynamics of infectious diseases: a population-based observational study using multi-source big data.

BACKGROUND: The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. METHODS: In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. RESULTS: In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ2 test for trend, P < 0.0001). Urban areas had a significantly higher ID than rural areas, with a relative risk of 1.25 (95% CI 1.23-1.27). Adolescents aged 10-19 years had the highest ID of varicella, women aged 20-39 years had significantly higher IDs of syphilis and trichomoniasis, and people aged ≥ 60 years had significantly higher IDs of zoster and viral conjunctivitis (all P < 0.05). CONCLUSIONS: Infectious diseases remain a substantial public health problem, and non-notifiable diseases should not be neglected. Multi-source-based big data are beneficial to better understand the profile and dynamics of infectious diseases.

Mettl3 promotes oxLDL-mediated inflammation through activating STAT1 signaling.

BACKGROUND: Atherosclerosis (AS) is the main cause of cerebrovascular diseases, and macrophages act important roles during the AS pathological process through regulating inflammation. Modification of the novel N(6)-methyladenine (m6A) RNA is reported to be associated with AS, but its role in AS is largely unknown. The aim of this study was to investigate the role and mechanism of m6A modification in inflammation triggered by oxidized low-density lipoprotein (oxLDL) in macrophages during AS. METHODS: RAW264.7 macrophage cells were stimulated with 40 µg/ml ox-LDL, Dot blot, Immunoprecipitation, western blot, Rip and chip experiments were used in our study. RESULTS: We found oxLDL stimulation significantly promoted m6A modification level of mRNA in macrophages and knockdown of Methyltransferase-Like Protein 3 (Mettl3) inhibited oxLDL-induced m6A modification and inflammatory response. Mettl3 promoted oxLDL-induced inflammatory response in macrophages through regulating m6A modification of Signal transducer and activator of transcription 1 (STAT1) mRNA, thereby affecting STAT1 expression and activation. Moreover, oxLDL stimulation enhanced the interaction between Mettl3 and STAT1 protein, promoting STAT1 transcriptional regulation of inflammatory factor expression in macrophages eventually. CONCLUSIONS: These results indicate that Mettl3 promotes oxLDL-triggered inflammation through interacting with STAT1 protein and mRNA in RAW264.7 macrophages, suggesting that Mettl3 may be as a potential target for the clinical treatment of AS.

Systematical characterization and comparison of saponins in Achyranthes bidentata Blume and its three analogous species.

INTRODUCTION: Achyranthes bidentata Blume (AB) has been used for a long time and is recorded in the Chinese Pharmacopoeia 2020 edition. It is commonly confused with Achyranthes aspera Linn (AA), Cyathula officinalis Kuan (CO) and Cyathula capitata (Wall.) Moq. (CC), belonging to the Achyranthes and Cyathula genera of the Amaranthaceae family. It is of great significance to recognize and distinguish chemical components of AB, AA, CO and CC. OBJECTIVE: The purpose of this study was to develop an analytical method for in-depth characterization and comparison of saponins in AB, AA, CO and CC. METHODS: The extracts of AB, AA, CO and CC were analyzed by an RP × RP (C18 × Phenyl-Hexyl) 2D LC system, eluted by acidic × ion pair mobile phases and detected by high resolution mass spectrometry. Fragmentation patterns of saponins were elucidated and proposed according to reference compounds or literature reports. RESULTS: As a result, 839 saponins consisting of 81, 415, 99 and 392 components corresponding to AB, AA, CO and CC, respectively, were characterized, including 594 potentially new saponins. Meanwhile, 29 kinds of aglycones were elucidated, among which 25 were new ones. Besides, 14, 91, 37 and 174 characteristic potential quality markers with MS intensities exceeding 10,000 were found in AB, AA, CO and CC, respectively. CONCLUSION: This comprehensive study not only expands our knowledge of the types of saponins in Achyranthes and Cyathula, but also reveals the differences among four kinds of analogous herbs (AB, AA, CO and CC), which facilitates the quality control of these herbal medicines in the future.

VWCE as a potential biomarker associated with immune infiltrates in breast cancer.

PURPOSE: Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. METHODS: The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. RESULTS: The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = - 0.12, p = 6e-05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. CONCLUSIONS: In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.

SCUBE3 serves as an independent poor prognostic factor in breast cancer.

BACKGROUND: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. METHODS: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. RESULTS: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2 + (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression. CONCLUSIONS: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

"Force iteration molecular designing" strategy for the systematic characterization and discovery of new protostane triterpenoids from Alisma Rhizoma by UHPLC/LTQ-Orbitrap-MS.

Comprehensive analysis and identification of chemical components are of great significance for evaluating the efficacy and safety of herbal medicines, as well as for drug exploitation and development. Here we developed a "force iteration molecular designing" strategy, by combing a database-based in-house software for a precursor ion list (PIL) and PIL-triggered collision-induced dissociation-MS2 and high-energy C-trap dissociation-MS2 (PIL-CID/MS2-HCD/MS2) on an LTQ-Orbitrap mass spectrometer, aiming for the systematic characterization and discovery of new protostane triterpenoids (PTs) from Alisma Rhizoma (AR). AR was a well-known herbal remedy widely used for diarrhea, but its systematic characterization and comparison between two botanical origins have not been reported. Firstly, in-house software was developed based on force iteration, to generate a PIL that contains 483 accurate precursor ions. Secondly, to facilitate the acquisition of rich fragments and diagnostic ions sufficient for the structural elucidation of different types of PTs, a hybrid data acquisition method, namely PIL-CID/MS2-HCD/MS2, was generated. Thirdly, a total of 473 PTs were rapidly characterized from two botanical origins of AR according to an established four-step interpretation method, and the common constituents were 277 with ratio 70% (277/395) and 78% (277/355) in the rhizome of Alisma plantago-aquatica and A. orientale, respectively. Finally, two new PTs were isolated and unambiguously identified by NMR verifying the feasibility of this combined data acquisition strategy. This integrated strategy could improve the efficiency in the detection of new compounds in a single run and is practical to comprehensively characterize the complex components in herbal medicines.

A strategy for practical authentication of medicinal plants in traditional Chinese medicine prescription, paeony root in ShaoYao-GanCao decoction as a case study.

Authentication of Chinese medicine materials in prescriptions is extremely difficult due to the complicated chemical matrix. A strategy integrating in-depth profiling, chemical marker selection, and selected detection was established and exemplarily applied to authenticate paeony root in ShaoYao-GanCao decoction. First, an ultra-performance liquid chromatography/linear trap quadrupole-Orbitrap method was developed to probe the chemical compositions of the decoction. Second, 20 batches of decoctions prepared from white paeony root and red paeony root were compared by a metabolomics method, and multistep chemometrics analysis distinguished the chemical markers. Third, an ultra-performance liquid chromatography/QDa-selected ion monitoring method was developed to authenticate the paeony root in decoctions. As a result, 161 compounds were characterized, including 84 triterpene saponins, 42 flavonoids, and 10 monoterpenes. Four chemical markers and paeoniflorin were successfully screened out as chemical markers for white paeony root. The selected ion monitoring method easily differentiated authentic decoction (prepared from white paeony root) from fraud decoction (prepared from red paeony root) by monitoring the above five chemical markers. In conclusion, the strategy was proved effective in authentication of paeony root in ShaoYao-GanCao decoction, and it can also be applied to authenticate other Chinese medicine materials in prescriptions, which will greatly avail the quality enhancement of prescriptions.

Silencing of lncRNA LBX2-AS1 suppresses glioma cell proliferation and metastasis through the Akt/GSK3ß pathway in vitro.

Long non-coding RNAs (lncRNAs) have been proposed to play pivotal roles in the tumorigenesis of various malignant tumors. Previous studies have found that lncRNA LBX2-AS1 is involved in the progression of various tumors. However, currently, the expression and exact mechanism of LBX2-AS1 in glioma remain unclear. In this study, using online-available datasets combined with clinical glioma tissues collected, we found that LBX2-AS1 was significantly increased and negatively correlated with prognosis in glioma. In vitro functional assays such as CCK-8, Annexin V, transwell assay, and western blot analysis showed that silencing of LBX2-AS1 suppressed the proliferation, migration, and invasion of glioma cells and increased apoptosis. RNA sequencing and western blot analysis confirmed that LBX2-AS1 regulates the Akt/GSK3ß pathway. In conclusion, this study showed that lncRNA LBX2-AS1 depletion inhibits the proliferation, migration, and invasion of glioma cells and increases apoptosis through the Akt/GSK3ß pathway. lncRNA LBX2-AS1 is expected to become a new target for glioma therapy.