Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19

Science China Life Sciences -     

HN1L promotes migration and invasion of breast cancer by up-regulating the expression of HMGB1

Recent reports showed that haematological and neurological expressed 1-like (HN1L) gene participated in tumorigenesis and tumour invasion. However, the expression and role of HN1L in breast cancer remain to be investigated. Here, bioinformatics, western blot and immunohistochemistry were used to detect the expression of HN1L in breast cancer. Wound healing, transwell assay, immunofluorescence assay and mass spectrum were used to explore the role and mechanism of HN1L on the migration and invasion of breast cancer, which was confirmed in vivo using a nude mice model. Results showed that HN1L was significantly over-expressed in breast cancer tissues, which was positively correlated with M metastasis of breast cancer patients. Silencing HN1L significantly inhibited the invasion and metastasis of breast cancer cells in vitro and lung metastasis in nude mice metastasis model of breast cancer. Mechanistically, HN1L interacted with HSPA9 and affected the expression of HMGB1, playing a key role in promoting the invasion and metastasis of breast cancer cell. These results suggested that HN1L was an appealing drug target for breast cancer.     

CDX2 enhances natural killer cell–mediated immunotherapy against head and neck squamous cell carcinoma through up-regulating CXCL14

(NK) cells are at the first line of defence against tumours, but their anti-tumour mechanisms are not fully understood. We aimed to investigate the mechanism by which NK cells can mediate immunotherapy against head and neck squamous cell carcinoma (HNSCC). We collected fifty-two pairs of HNSCC tissues and corresponding adjacent normal tissues; analysis by RT-qPCR showed underexpression of CXCL14 in HNSCC tissues. Primary NK cells were then isolated from the peripheral blood of HNSCC patients and healthy donors. CXCL14 was found to be consistently under-expressed in the primary NK cells from the HNSCC patients. However, CXCL14 expression was increased in IL2-activated primary NK cells and NK-92 cells. We next evaluated NK cell migration, IFN-γ and TNF-α expression, cytotoxicity and infiltration in response to CXCL14 overexpression or knockdown using gain- and loss-of-function approach. The results exhibited that CXCL14 overexpression promoted NK cell migration, cytotoxicity and infiltration. Subsequent in vivo experiments revealed that CXCL14 suppressed the growth of HNSCC cells via activation of NK cells. ChIP was applied to study the enrichment of H3K27ac, p300, H3K4me1 and CDX2 in the enhancer region of CXCL14, which showed that CDX2/p300 activated the enhancer of CXCL14 to up-regulate its expression. Rescue experiments demonstrated that CDX2 stimulated NK cell migration, cytotoxicity and infiltration through up-regulating CXCL14. In vivo data further revealed that CDX2 suppressed tumorigenicity of HNSCC cells through enhancement of CXCL14. To conclude, CDX2 promotes CXCL14 expression by activating its enhancer, which promotes NK cell–mediated immunotherapy against HNSCC.     

ARL4C might serve as a prognostic factor and a novel therapeutic target for gastric cancer: bioinformatics analyses and biological experiments

The ADP-ribosylation factor-like proteins (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. In this study, we systematically investigate the expression status, interactive relations, potential pathways, genetic variations and clinical values of ARLs in GC. We find that ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant clinical indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that ARL4C is highly correlated with TGF-β1 signalling. Correspondingly, TGF-β1 treatment dramatically increases ARL4C expression and ARL4C knockdown inhibits the phosphorylation level of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients. Our work comprehensively demonstrates the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients.     

莫古礼(Floyd Alonzo McClure)在华采集和引种竹类植物的历史及其影响

竹类植物是美国采集者在我国采集和引种的一类主要植物。在众多的竹类植物采集者中, 莫古礼(Floyd Alonzo McClure)是最具代表性的一位, 他于1919-1940年在岭南大学开展竹类植物研究, 在此期间多次采集竹类植物标本并引种竹类植物到美国。本研究通过大量文献研究、档案查阅以及实地调研, 整理了莫古礼采集竹类植物的路线和采集地, 并对竹类植物学名进行校对, 分析了莫古礼在华研究、采集和引种竹类植物的历史及其影响。经统计, 莫古礼在华期间竹类植物标本采集地涉及12个省级行政区39个地级市, 主要集中在广东、海南、香港等地; 引种地涉及9个省级行政区的25个地级市; 共采集竹类植物标本727号1,840份, 隶属20属93种(含种下单位, 下同), 分别占我国竹类植物属和种的58.8%和17.4%; 共引种竹类植物255份, 隶属于17属77种, 分别占我国竹类植物属和种的50.0%和14.4%。莫古礼在华采集和引种竹类植物极大地发展了竹类植物分类学, 所采集的竹类植物标本为后人竹类植物研究提供了极大的帮助, 所引种的竹类植物极大丰富了美国竹类植物种类, 也促进了竹类植物在美国的应用。     

Polymorphism of Fecundity Genes (FecB,FecX, and FecG) in the Indian Bonpala Sheep

The 37-kDa laminin receptor precursor/67-kDa laminin receptor (LRP/LR, also known as ribosomal protein SA, RPSA) has been reported to be involved in cancer development and prion internalization. Previous studies have shown that the LRP/LR is expressed in a wide variety of tissues. In particular, expression of LRP/LR mRNA may be closely related to the degree of PrP^Sc propagation. This study presents a detailed investigation of the LRP/LR mRNA expression levels in eleven normal ovine tissues. Using real-time quantitative PCR, the highest LRP/LR expression was found in neocortex (p < 0.05). Slightly lower levels were found in the heart and obex. Intermediate levels were seen in hippocampus, cerebellum, spleen, thalamus, mesenteric lymph node, and the lowest levels were present in liver, kidney, and lung. In general, the LRP/LR mRNA levels were much higher in neuronal tissues than in peripheral tissues. The observation that differences in LRP/LR mRNA expression levels are consistent with the corresponding variation in PrP^Sc accumulation suggests that the 37-kDa/67-kDa laminin receptor may be involved in the regulation of PrP^Sc propagation.     

Mediation of Clathrin-Dependent Trafficking during Cytokinesis and Cell Expansion by Arabidopsis STOMATAL CYTOKINESIS DEFECTIVE Proteins

STOMATAL CYTOKINESIS DEFECTIVE1 (SCD1) encodes a putative Rab guanine nucleotide exchange factor that functions in membrane trafficking and is required for cytokinesis and cell expansion in Arabidopsis thaliana. Here, we show that the loss of SCD2 function disrupts cytokinesis and cell expansion and impairs fertility, phenotypes similar to those observed for scd1 mutants. Genetic and biochemical analyses showed that SCD1 function is dependent upon SCD2 and that together these proteins are required for plasma membrane internalization. Further specifying the role of these proteins in membrane trafficking, SCD1 and SCD2 proteins were found to be associated with isolated clathrin-coated vesicles and to colocalize with clathrin light chain at putative sites of endocytosis at the plasma membrane. Together, these data suggest that SCD1 and SCD2 function in clathrin-mediated membrane transport, including plasma membrane endocytosis, required for cytokinesis and cell expansion.     

Prevention of Hemodynamic Instability in Extra-Cranial Carotid Angioplasty and Stenting Using Temporary Transvenous Cardiac Pacemaker

Hemodynamic instability is a common condition during extra-cranial carotid angioplasty and stenting (CAS). We evaluated the safety and efficacy of prophylactic placement of temporary cardiac pacemaker during extra-cranial CAS for the prevention of hemodynamic instability. For this, forty-seven carotid artery stents were deployed in 41 high-risk patients. Temporary transvenous cardiac pacemakers were inserted before CAS procedure. The pacers were set to capture a heart rate <60 bpm. Clinical symptoms, blood pressure, heart rate, and pacing activation were monitored and data were collected. We found that pacing occurred in 25 carotid lesions during balloon predilatation; pacemakers were activated transiently in 25 patients. The longest pacing continued for 1 day. Among cases with pacemaker activation, 1 patient developed post-procedural symptomatic hypotension that lasted for 4 days. No related complications were observed. It was, therefore, concluded that pacing was technically effective in producing electrical ventricular responses and was hemodynamically effective in 25 carotid lesions which underwent balloon predilatation. The prophylactic use of a temporary transvenous cardiac pacemaker during CAS was rapid and effective in controlling peri-operative hemodynamic instability and preventing stroke and other complications. The prophylactic use of temporary pacemaker is particularly recommended for patients at high risk for developing hemodynamic instability.     

Surface Properties and Corrosion Behavior of Co–Cr Alloy Fabricated with Selective Laser Melting Technique

We sought to study the corrosion behavior and surface properties of a commercial cobalt–chromium (Co–Cr) alloy which was fabricated with selective laser melting (SLM) technique. For this purpose, specimens were fabricated using different techniques, such as SLM system and casting methods. Surface hardness testing, microstructure observation, surface analysis using X-ray photoelectron spectroscopy (XPS) and electrochemical corrosion test were carried out to evaluate the corrosion properties and surface properties of the specimens. We found that microstructure of SLM specimens was more homogeneous than that of cast specimens. The mean surface hardness values of SLM and cast specimens were 458.3 and 384.8, respectively; SLM specimens showed higher values than cast ones in hardness. Both specimens exhibited no differences in their electrochemical corrosion properties in the artificial saliva through potentiodynamic curves and EIS, and no significant difference via XPS. Therefore, we concluded that within the scope of this study, SLM-fabricated restorations revealed good surface properties, such as proper hardness, homogeneous microstructure, and also showed sufficient corrosion resistance which could meet the needs of dental clinics.