CXCR4 is required for the quiescence of primitive hematopoietic cells

The quiescence of hematopoietic stem cells (HSCs) is critical for preserving a lifelong steady pool of HSCs to sustain the highly regenerative hematopoietic system. It is thought that specialized niches in which HSCs reside control the balance between HSC quiescence and self-renewal, yet little is known about the extrinsic signals provided by the niche and how these niche signals regulate such a balance. We report that CXCL12 produced by bone marrow (BM) stromal cells is not only the major chemoattractant for HSCs but also a regulatory factor that controls the quiescence of primitive hematopoietic cells. Addition of CXCL12 into the culture inhibits entry of primitive hematopoietic cells into the cell cycle, and inactivation of its receptor CXCR4 in HSCs causes excessive HSC proliferation. Notably, the hyperproliferative Cxcr4−/− HSCs are able to maintain a stable stem cell compartment and sustain hematopoiesis. Thus, we propose that CXCR4/CXCL12 signaling is essential to confine HSCs in the proper niche and controls their proliferation

Gluon Condensation Signature in the GeV Gamma-Ray Spectra of Pulsars

The accumulation of gluons inside nucleons, i.e., the gluon condensation, may lead to a characteristic broken power-law gamma-ray spectrum in high-energy nucleon collisions. Here we show that the observed spectra of at least 25 sources in the second Fermi Large Area Telescope Catalog of Gamma-ray Pulsars can be well fitted by such a broken power-law function that has only four free parameters. It strongly indicates that the gamma-ray emission from these pulsars is of hadronic origin, but with gluon condensation inside hadrons. It is well known that the quark-gluon distribution in a free nucleon is different from that in a bound nucleon. This work exposes the nuclear $A$-dependence of the gluon condensation effect, where $A$ refers to the baryon number. Our study reveals the gluon condensation under the condition of $A\to\infty$, which may open a new window for eavesdropping on the structure of compact stars on the sub-nuclear level.Comment: 12 pages (9 pages for main text), 5 figures, 1 table, accepted by PRD at https://journals.aps.org/prd/accepted/fd07cQ89M2118d20490d0d014fdd00616d4cdeb8

The Role of CXCR4 in Maintaining Peripheral B Cell Compartments and Humoral Immunity

The chemokine receptor CXCR4 is expressed in B cells at multiple stages of their development. CXCR4 function in humoral immunity has not been fully investigated. We have generated gene-targeted mice in which CXCR4 can be selectively inactivated in B cells and have shown that it is required for retention of B cell precursors in the bone marrow. CXCR4-deficient B cell precursors that migrated prematurely became localized in splenic follicles despite their unresponsiveness to CXCL13. Concomitantly, mature B cell populations were reduced in the splenic marginal zone and primary follicles, and in the peritoneal cavity in the mutant animals, as were T-independent antibody responses. In addition, aberrant B cell follicles formed ectopically in intestinal lamina propria around Peyer's patches. These findings establish an important role for CXCR4 in regulating homeostasis of B cell compartmentalization and humoral immunity

Hederagenin from the leaves of ivy (Hedera helix L.) induces apoptosis in human LoVo colon cells through the mitochondrial pathway

BACKGROUND: Colorectal cancer has become one of the leading cause of cancer morbidity and mortality throughout world. Hederagenin, a derivative of oleanolic acid isolated from the leaves of ivy (Hedera helix L.), has been shown to have potential anti-tumor activity. The study was conducted to evaluate whether hederagenin could induce apoptosis of human colon cancer LoVo cells and explore the possible mechanism. METHODS: MTT assay was used for evaluating cell viability while Annexin V-FITC/PI assay and Hoechst 33342 nuclear stainining were used for the determination of apoptosis and mitochondrial membrane potential. DCFH-DA fluorescence staining and flow cytometry were used to measure ROS generation. Real-time PCR and western blot analysis were performed for apoptosis-related protein expressions. RESULTS: MTT assay showed that hederagenin could significantly inhibit the viability of LoVo cells in a concentration-dependent and time-dependent manner by IC(50) of 1.39 μM at 24 h and 1.17 μM at 48 h. The apoptosis ratio was significantly increased to 32.46% and 81.78% by the induction of hederagenin (1 and 2 μM) in Annexin V-FITC/PI assay. Hederagenin could also induce the nuclear changes characteristic of apoptosis by Hoechst 33342 nuclear stainining under fluorescence microscopy. DCFH-DA fluorescence staining and flow cytometry showed that hederagenin could increase significantly ROS generation in LoVo cells. Real-time PCR showed that hederagenin induced the up-regulation of Bax and down-regulation of Bcl-2, Bcl-xL and Survivin. Western blotting analysis showed that hederagenin decreased the expressions of apoptosis-associated proteins Bcl-2, procaspase-9, procaspase-3, and polyADP- ribosepolymerase (PARP) were increased, while the expressions of Bax, caspase-3, caspase-9 were increased. However, there was no significant change on caspase-8. CONCLUSIONS: These results indicated that the disruption of mitochondrial membrane potential might contribute to the apoptosis of hederagenin in LoVo cells. Our findings suggested that hederagenin might be a promising therapeutic candidate for human colon cancer

HI content of massive red spiral galaxies observed by FAST

A sample of 279 massive red spirals was selected optically by Guo et al. (2020), among which 166 galaxies have been observed by the ALFALFA survey. In this work, we observe HI content of the rest 113 massive red spiral galaxies using the Five-hundred-meter Aperture Spherical radio Telescope (FAST). 75 of the 113 galaxies have HI detection with a signal-to-noise ratio (S/N) greater than 4.7. Compared with the red spirals in the same sample that have been observed by the ALFALFA survey, galaxies observed by FAST have on average a higher S/N, and reach to a lower HI mass. To investigate why many red spirals contain a significant amount of HI mass, we check color profiles of the massive red spirals using images observed by the DESI Legacy Imaging Surveys. We find that galaxies with HI detection have bluer outer disks than the galaxies without HI detection, for both ALFALFA and FAST samples. For galaxies with HI detection, there exists a clear correlation between galaxy HI mass and g-r color at outer radius: galaxies with higher HI masses have bluer outer disks. The results indicate that optically selected massive red spirals are not fully quenched, and the HI gas observed in many of the galaxies may exist in their outer blue disks.Comment: 11 pages, 9 figures, accepted by MNRAS; Table 1 is available in the source file

Plasma MicroRNA Pair Panels as Novel Biomarkers for Detection of Early Stage Breast Cancer

Introduction: Breast cancer is the second leading cause of cancer death among females. We sought to identify microRNA (miRNA) markers in breast cancer, and determine whether miRNA expression is predictive of early stage breast cancer. The paired panel of microRNAs is promising.Methods: Global miRNA expression profiling was performed on three pooling samples of plasma from breast cancer, benign lesion and normal, using next generation sequencing technology. Thirteen microRNAs (hsa-miR-21-3p, hsa-miR-192-5p, hsa-miR-221-3p, hsa-miR-451a, hsa-miR-574-5p, hsa-miR-1273g-3p, hsa-miR-152, hsa-miR-22-3p, hsa-miR-222-3p, hsa-miR-30a-5p, hsa-miR-30e-5p, hsa-miR-324-3p, and hsa -miR-382-5p) were subsequently validated using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) in a cohort of 53 breast cancer, 40 benign lesions and 38 normal cases. The pairwise miRNA ratios were calculated as biomarkers to classify breast cancer.Results: According to the model used to predict breast cancer from benign lesions, a panel of five miRNA pairs had high diagnostic power with an AUC of 0.942. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of this model after 10-fold cross validation were 0.881, 0.775, 0.827, and 0.756, respectively. In addition, the other panels of miRNA pairs distinguishing the breast cancer from normal and non-cancer patients had good performance.Conclusion: Certain MicroRNA pairs were identified and deemed effective in breast cancer screening, especially when distinguishing cancer from benign lesions

De novel heterozygous copy number deletion on 7q31.31-7q31.32 involving TSPAN12 gene with familial exudative vitreoretinopathy in a Chinese family

AIM: To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32. METHODS: A family with familial exudative vitreoretinopathy (FEVR) phenotype was included in the study. Whole-exome sequencing (WES) was initially used to locate copy number variations (CNVs) on 7q31.31-31.32, but failed to detect the precise breakpoint. The long-read sequencing, Oxford Nanopore sequencing Technology (ONT) was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction (QPCR) and Sanger Sequencing. RESULTS: The proband, along with her father and younger brother, were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32, which included the FEVR-related gene TSPAN12. The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del. The proband exhibited a phase 2A FEVR phenotype, characterized by a falciform retinal fold, macular dragging, and peripheral neovascularization with leaking of fluorescence. These symptoms led to a significant decrease in visual acuity in both eyes. On the other hand, the affected father and younger brother showed a milder phenotype. CONCLUSION: The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype. The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders

Organoleptic Evaluation of Amomi Fructus and Its Further Background Verified via Morphological Measurement and GC Coupled with E-Nose

The present study investigated the maneuverability and reasonability of sensory analysis, which has been applied in TCM identification for a long time. Ten assessors were trained and generated the human panel to carry out the organoleptic evaluation of twenty-five batches of Sha-Ren samples. Accordingly, samples were scored from 0 (lowest) to 10 (highest) for sensory attributes. Based on this, samples were divided into three classes: high class (Yang-Chun-Sha from Guang-Dong), moderate class (Yang-Chun-Sha samples from Yun-Nan and Guang-Xi), and low class (Lv-Qiao-Sha from marketplaces). For further background, three instrumental approaches were employed: morphological measurement with three indices (longitudinal diameter, transverse diameter, and 100-fruit weight), GC for determination of bornyl acetate contents, and E-nose for aromatic fingerprint. It is demonstrated in the results that GC and E-nose analyses were in great agreement with organoleptic evaluation. It gives insights into further studies on searching better morphological indicators and improving discriminant model of E-nose