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This work reports the synthesis of chiral perovskite heterostructure films by combining a two-dimensional (2D) chiral (R-/S-MBA)2PbI4 perovskite with CsPbBr3 quantum dots (QDs). The as-synthesized chiral heterostructure films exhibit obvious circularly polarized luminescence (CPL) properties, even though pure 2D chiral perovskite cannot present photoluminescence. It indicates that the chirality of the excited state of the QDs originates from the 2D chiral perovskite. The circular polarization-resolved transient absorption (TA) spectra further demonstrate that the CPL response of heterostructure films originates from the energy transfer between the chiral perovskite layer and QDs layer and the suppression of spin relaxation, which induces the imbalance of the spin population of excited states in QDs layer. In addition, the photoluminescence (PL), circular dichroism (CD), and CPL spectra of these heterostructure films can be controlled by varying the thickness and component of the chiral perovskite layer, which demonstrates that the anion exchange between chiral perovskite and CsPbBr3 QDs can tune the chemical composition and optoelectronic properties due to the low bonding energy difference between them and decrease the strain within the QDs layer to reduce the radiative recombination lifetime. This work provides guidance for the synthesis of chiral perovskites with a strong CPL response and further provides insight into the origination of CPL.
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The Holocene temperature conundrum, the discrepancy between proxy-based Holocene global cooling and simulated global annual warming trends, remains controversial. Meanwhile, reconstructions and simulations show inconsistent spatial patterns of terrestrial temperature changes. Here we report Holocene alkenone records to address spatial patterns over mid-latitude Eurasia. In contrast with long-term cooling trends in warm season temperatures in northeastern China, records from southwestern Siberia are characterized by colder conditions before ~6,000 years ago, thus long-term warming trends. Together with existing records from surrounding regions, we infer that colder airmass might have prevailed in the interior of mid-latitude Eurasian continent during the early to mid-Holocene, perhaps associated with atmospheric response to remnant ice sheets. Our results challenge the proposed seasonality bias in proxies and modeled spatial patterns in study region, highlighting that spatial patterns of Holocene temperature changes should be re-considered in record integrations and model simulations, with important implications for terrestrial hydroclimate changes.
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2D lead halide perovskites (LHPs) show strong excitonic and spin-orbit coupling effects, generating a facile spin injection. Besides, they possess a polaron character due to the soft crystal lattice, which can prolong the spin lifetime, making them favorable materials for spintronic applications. Here, the spin dynamics of 2D PEA2 PbI4 (MAPbI3 )n -l thin films with different layers by temperature- and pump fluence-dependent circularly polarization-resolved transient absorption (TA) measurements is studied. These results indicate that the spin depolarization mechanism is gradually converted from the Maialle-Silva-Sham (MSS) mechanism to the polaronic states protection mechanism with the layer number increasing from
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BACKGROUND: Posttranscriptional modification of tumor-associated factors plays a pivotal role in breast cancer progression. However, the underlying mechanism remains unknown. M6A modifications in cancer cells are dynamic and reversible and have been found to impact tumor initiation and progression through various mechanisms. In this study, we explored the regulatory mechanism of breast cancer cell proliferation and metabolism through m6A methylation in the Hippo pathway. METHODS: A combination of MeRIP-seq, RNA-seq and metabolomics-seq was utilized to reveal a map of m6A modifications in breast cancer tissues and cells. We conducted RNA pull-down assays, RIP-qPCR, MeRIP-qPCR, and RNA stability analysis to identify the relationship between m6A proteins and LATS1 in m6A regulation in breast cancer cells. The expression and biological functions of m6A proteins were confirmed in breast cancer cells in vitro and in vivo. Furthermore, we investigated the phosphorylation levels and localization of YAP/TAZ to reveal that the activity of the Hippo pathway was affected by m6A regulation of LATS1 in breast cancer cells. RESULTS: We demonstrated that m6A regulation plays an important role in proliferation and glycolytic metabolism in breast cancer through the Hippo pathway factor, LATS1. METTL3 was identified as the m6A writer, with YTHDF2 as the reader protein of LATS1 mRNA, which plays a positive role in promoting both tumorigenesis and glycolysis in breast cancer. High levels of m6A modification were induced by METTL3 in LATS1 mRNA. YTHDF2 identified m6A sites in LATS1 mRNA and reduced its stability. Knockout of the protein expression of METTL3 or YTHDF2 increased the expression of LATS1 mRNA and suppressed breast cancer tumorigenesis by activating YAP/TAZ in the Hippo pathway. CONCLUSIONS: In summary, we discovered that the METTL3-LATS1-YTHDF2 pathway plays an important role in the progression of breast cancer by activating YAP/TAZ in the Hippo pathway.
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Neoplasias de la Mama , Humanos , Femenino , Metilación , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Transformación Celular Neoplásica/genética , Carcinogénesis/genética , Factores de Transcripción/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismoRESUMEN
The interaction between organic cations and inorganic metal halide octahedral units strongly affects the properties of organic-inorganic hybrid metal halides. The "soft" property of the lattice provides the possibility of its strong exciton-phonon interaction. Here we report one-dimensional (1D) lead-free chiral organic-inorganic hybrid metal halide single crystals of (R/S)-methylbenzylamine bismuth iodide (R/S-MBA)2Bi2I8, which exhibits a high level of octahedral bond distortion. The introduction of chiral amines leads to a strong chiroptical response in the range of 200-600 nm. The strong exciton-phonon coupling can be observed through the coherent oscillation spectrum of transient absorption dynamics at room temperature. The coherent phonon oscillation frequencies are â¼97 and â¼130 cm-1, corresponding to the symmetrical stretching or bending of the Bi-I octahedron. Our work provides new insights for the study of exciton-phonon coupling in 1D chiral hybrid metal halides.
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Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus displayed remarkable efficacy against authentic B.1.351 virus. Each of these 3 mAbs in combination with one neutralizing Ab recognizing non-competing epitope exhibited synergistic effect against authentic SARS-CoV-2 virus. Surprisingly, structural analysis revealed that 58G6 and 13G9, encoded by the IGHV1-58 and the IGKV3-20 germline genes, both recognized the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly bound to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrated prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. These 2 ultrapotent neutralizing Abs can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.
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BACKGROUND: The DNA-binding protein RFX6 was overexpressed in hepatocellular carcinoma, and its expression level was correlated with the prognosis and immune cell infiltration in liver hepatocellular carcinoma. However, the mechanism of the abnormal expression and the biological effects of RFX6 in liver cancer remains unknown. METHODS: To understand the specific expression mechanism of RFX6 in liver cancer, we performed bioinformatic prediction, CHIP-qPCR assay, co-IP, and dual-luciferase assay to assess the regulating mechanism of RFX6. In the meantime, a series of biological experiments in vivo and in vitro were conducted to analyze the biological significance of RFX6 in hepatocellular carcinoma. RESULTS: We demonstrated that knockdown of RFX6 in liver cancer cells significantly suppressed the proliferation, migration, and invasion of cancer cells. Moreover, inhibition of RFX6 could affect the immune response of T cells. Among a number of interacting proteins, we revealed that RFX6 directly binds to DTX2, a regulator of the Notch signaling pathway by targeting NOTCH1, and helps in its transcription stability. Furthermore, we discovered that miRNA-542-3p, the expression of which was decreased in hepatocellular carcinoma, was directly involved in the negative regulation of the expression of RFX6. CONCLUSION: In summary, we discovered that the miRNA-542-3p-RFX6-DTX2-NOTCH1 regulatory pathway played significant roles in the tumor progression of liver hepatocellular carcinoma.
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The spread of SARS-CoV-2 confers a serious threat to the public health without effective intervention strategies1-3. Its variant carrying mutated Spike (S) protein D614G (SD614G) has become the most prevalent form in the current global pandemic4,5. We have identified a large panel of potential neutralizing antibodies (NAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 S6. Here, we focused on the top 20 potential NAbs for the mechanism study. Of them, the top 4 NAbs could individually neutralize both authentic SARS-CoV-2 and SD614G pseudovirus efficiently. Our epitope mapping revealed that 16/20 potent NAbs overlapped the same steric epitope. Excitingly, we found that one of these potent NAbs (58G6) exclusively bound to a linear epitope on S-RBD (termed as 58G6e), and the interaction of 58G6e and the recombinant ACE2 could be blocked by 58G6. We confirmed that 58G6e represented a key site of vulnerability on S-RBD and it could positively react with COVID-19 convalescent patients plasma. We are the first, as far as we know, to provide direct evidences of a linear epitope that can be recognized by a potent NAb against SARS-CoV-2 S-RBD. This study paves the way for the applications of these NAbs and the potential safe and effective vaccine design.
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Neutralizing antibodies (Abs) have been considered as promising therapeutics for the prevention and treatment of pathogens. After the outbreak of COVID-19, potent neutralizing Abs to SARS-CoV-2 were promptly developed, and a few of those neutralizing Abs are being tested in clinical studies. However, there were few methodologies detailly reported on how to rapidly and efficiently generate neutralizing Abs of interest. Here, we present a strategically optimized method for precisive screening of neutralizing monoclonal antibodies (mAbs), which enabled us to identify SARS-CoV-2 receptor-binding domain (RBD) specific Abs within 4 days, followed by another 2 days for neutralization activity evaluation. By applying the screening system, we obtained 198 Abs against the RBD of SARS-CoV-2. Excitingly, we found that approximately 50% (96/198) of them were candidate neutralizing Abs in a preliminary screening of SARS-CoV-2 pseudovirus and 20 of these 96 neutralizing Abs were confirmed with high potency. Furthermore, 2 mAbs with the highest neutralizing potency were identified to block authentic SARS-CoV-2 with the half-maximal inhibitory concentration (IC50) at concentrations of 9.88 ng/ml and 11.13 ng/ml. In this report, we demonstrated that the optimized neutralizing Abs screening system is useful for the rapid and efficient discovery of potent neutralizing Abs against SARS-CoV-2. Our study provides a methodology for the generation of preventive and therapeutic antibody drugs for emerging infectious diseases.
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BACKGROUND/AIMS: Arctigenin (ATG) has been shown to possess anti-inflammatory, immunemodulatory, anti-viral, anti-microbial, anti-carcinogenic, vasodilatory and anti-platelet aggregation properties. However, the protective role of ATG in prevention of arrhythmias induced by myocardial ischemia/reperfusion is unknown. The aim of this study was to investigate the anti-arrhythmia effect of ATG in an ischemia/reperfusion injured rat heart model and explore the related mechanisms. METHODS: Rats were randomly exposed to sham operation, myocardial ischemia/ reperfusion (MI/R) alone, ATG+ MI/R, pretreated with ATG in low (12.5 mg/kg/day), medium (50 mg/kg/day) and high dose (200 mg/kg/day), respectively. Ventricular arrhythmias were assessed. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of malondialdehyde (MDA) in myocardial tissue were determined by chemical analysis. RESULTS: Compared to MI/R, rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/day showed significantly reduced incidence and duration of ventricular fibrillation, ventricular tachycardia and ventricular ectopic beat (VEB), and decreased the arrhythmia score during the 30-min ischemia. Incidence and duration of ventricular tachycardia, infarction size and arrhythmia scores in these groups were significantly decreased during the 120-min reperfusion. No ventricular fibrillation occurred during the period of reperfusion. Rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/ day markedly enhanced the activities of antioxidant enzymes SOD and GSH-Px, reduced the level of MDA. No differences were observed between the group pretreated with a low dose of ATG and the sham group. Administration of ATG significantly increased the expression of antioxidant stress protein Nrf2, Trx1 and Nox1. CONCLUSION: Our data suggested that ATG plays anti-arrhythmia role in ischemia/reperfusion injury, which is probably associated with attenuating oxidative stress by Nrf2 signaling pathway.
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Arritmias Cardíacas/prevención & control , Furanos/farmacología , Lignanos/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Arritmias Cardíacas/etiología , Arritmias Cardíacas/metabolismo , Modelos Animales de Enfermedad , Furanos/uso terapéutico , Glutatión Peroxidasa/metabolismo , Lignanos/uso terapéutico , Masculino , Malondialdehído/metabolismo , Infarto del Miocardio/patología , Miocardio/metabolismo , NADPH Oxidasa 1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/complicaciones , Superóxido Dismutasa/metabolismo , Tiorredoxinas/metabolismoRESUMEN
In our study, we report on the design and characterization of a combined angiogenesis therapy for breast cancer based on well-formed amine-functionalized silica nanoparticles (SLNs). The aminefunctionalized SLNs was employed to simultaneously deliver angiostatin (ANG) plasmid and candesartan (CD) to the same cancer cell. The well-formed ANG/CD/SLNs exhibited small particle size, reasonable positive charges, excellent loading of drug and gene in vitro. Moreover, aminefunctionalized SLNs were almost no cytotoxicity. ANG/CD/SLNs resulted in enhanced gene transfection compared to naked plasmid. More importantly, ANG/CD/SLNs as a co-delivery system achieved a stronger inhibitory effect on angiogenesis in vitro, possibly resulting from significant downregulation of vascular endothelial growth factor (VEGF) expression via different pathways. In particular, in vivo investigation on nude mice bearing MCF-7 xenografts confirmed that ANG/CD/SLNs codelivery system exerted strong anti-tumor efficacy by synergistic antiangiogenic mechanism.
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Aminas/química , Neoplasias de la Mama/terapia , Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Nanopartículas , Dióxido de Silicio/química , Animales , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Desnudos , Factor A de Crecimiento Endotelial VascularRESUMEN
Objective To study the effect of age on the trajectory of the center of plantar pressure.Methods Twenty-five healthy young people constituted a youth group,while another 25 elderly counterparts formed an aged group.Descriptors of everyone's gait were collected using an AL-600 gait and balance training and evaluation apparatus.The length of the total trajectory of the center of plantar pressure (COPD) was recorded along with the average left and right deviation of the center of plantar pressure (COPD-X) and its average anterior-posterior deviation (COPD-Y) in the heel strike (LR),single plantar stance (SPS) and push-off (PS) phases of striding.Results The average COPD of the aged group was significantly longer than that of the youths.For both groups,the average COPD-X and COPD-Y deviations in SPS were significantly less than those in the LR and PS phases,with no significant difference between them.Compared with the youth group,the average COPD-X in the LR and PS phases and the average COPD-Y in the PS were significantly greater among the aged,but there was no significant difference between the two groups in the average COPD-X in SPS or in the average COPD-Y in the LR and SPS phases.Conclusions The average COPD,COPD-X and COPD-Y increase with age,indicating the higher risk of falling.The changes in each sub-phase of gait are different,but those in the LR and PS phases more reliably reflect stability.
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BACKGROUND Osteomyelitis is one of the refractory diseases encountered in orthopedics, while Staphylococcus aureus (S. aureus) is the most common causative organism in osteomyelitis. However, the precise mechanisms underlying the bone loss caused by S. aureus infection have not been well defined. Here, we investigated the effect of S. aureus on osteoclast differentiation and the probable molecular mechanism. MATERIAL AND METHODS RAW 264.7 cells were treated for 5 days with live S. aureus, inactivated S. aureus, and S. aureus filtrate. Then, the formation of osteoclast-like cells and resorption pits was observed, and the expression of osteoclast-specific genes (TRAP, MMP-9, cathepsin K, CTR and Atp6v0d2) was detected by real-time PCR. Moreover, key proteins in the signaling pathway associated with osteoclast differentiation were detected with Western blot. RESULTS The data showed that live S. aureus, inactivated S. aureus, and S. aureus filtrate induced osteoclast formation, promoted bone resorption, and increased the expression of osteoclast-specific genes in a dose-dependent manner in the absence RANKL. In addition, we found that the S. aureus-induced osteoclastogenesis was related to the degradation of IκB-a, phosphorylation of NF-κB p65, and increased expression of NFATc1. Thus, we used JSH-23 to inhibit NF-κB transcriptional activity. The effect of the S. aureus-induced osteoclastogenesis and the expression of osteoclast-specific genes and NFATc1 were inhibited, which indicated that the NF-κB signaling pathway plays a role in S. aureus-induced osteoclastogenesis. CONCLUSIONS This study demonstrated that S. aureus induces osteoclastogenesis through its cell wall compound and secretion of small soluble molecules, and the NF-κB signaling pathway plays a role in this process.
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FN-kappa B/fisiología , Osteogénesis/efectos de los fármacos , Staphylococcus aureus/patogenicidad , Animales , Resorción Ósea/metabolismo , Resorción Ósea/microbiología , Diferenciación Celular/fisiología , Regulación de la Expresión Génica/genética , Macrófagos/metabolismo , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/inmunología , FN-kappa B/metabolismo , Subunidad p52 de NF-kappa B/fisiología , Factores de Transcripción NFATC , Osteoclastos/metabolismo , Osteoclastos/microbiología , Osteogénesis/inmunología , Osteogénesis/fisiología , Osteomielitis/microbiología , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Staphylococcus aureus/metabolismo , Factor de Transcripción ReIA/metabolismoRESUMEN
BACKGROUND: Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) was found to be participated in tumorigenesis in various cancers including hepatocellular carcinoma (HCC). However, the clinical implication and underling function of NEAT1 in HCC have not been fully known. METHODS: The relative NEAT1 expression was examined by qRT-PCR in HCC tissues and cells, compared with adjacent normal tissues and normal human hepatocyte (LO2) cells, respectively. Cell proliferation and invasion were examined by MTT, cell colony formation and transwell assays. Luciferase reporter assay was performed to verify miR-613 was a direct target of NEAT1. Western blot analysis was also performed. RESULTS: NEAT1 was notably upregulated in HCC tissues and cells. Higher NEAT1 expression associated with larger tumor size and vascular invasion of HCC patients. Knockdown of NEAT1 significantly suppressed HCC cell proliferation, colony formation and cell invasion. Interestingly, lower miR-613 expression negatively associated with the NEAT1 expression in HCC tissues and was regulated by NEAT1. Additionally, we demonstrated that NEAT1 promoted HCC cell proliferation and invasion by regulating miR-613 expression. CONCLUSION: These results implied that inhibition of NEAT1 may be a potential therapeutic strategy for HCC patients.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Técnicas de Silenciamiento del Gen , Hepatocitos/metabolismo , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia ArribaRESUMEN
Staphylococcus aureus (S. aureus) is the most common organism causing osteomyelitis, and Staphylococcus aureus protein A (SpA) is an important virulence factor anchored in its cell wall. However, the precise mechanisms underlying the bone loss caused by SpA have not been well understood. The present study aimed to investigate the effect of SpA on osteoclast differentiation, and the probable mechanism was investigated. Raw264.7 cells were treated with SpA in the absence or presence of receptoractivated (NF)κB ligand for 5 days, and morphological and biochemical assays were used to assess osteoclastogenesis and explore the underlying mechanisms. Data demonstrated that SpA induced osteoclast differentiation and promoted bone resorption in a dosedependent manner in the absence or presence of RANKL. In addition, the expression of osteoclastspecific genes, such as the tartrate resistant acid phosphatase, matrix metalloproteinase9, cathepsin K, calcitonin receptors and d2 isoform of the vacuolar ATPase Vo domain, were enhanced by SpA. Furthermore, the SpAinduced osteoclast differentiation was associated with the degradation of inhibitor of κBα, phosphorylation of NFκB p65 and increased expression of nuclear factor of activated Tcells. However, by treatment with JSH23, an NFκB inhibitor, the formation of osteoclastlike cells and resorption pits was significantly reduced, and the expression of osteoclastspecific genes was also inhibited. Collectively, in the present study SpA induced osteoclast differentiation, promoted bone resorption, and the NFκB signaling pathway was involved in this process.
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FN-kappa B/metabolismo , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteína Estafilocócica A/farmacología , Animales , Catepsina K/genética , Catepsina K/metabolismo , Diferenciación Celular , Regulación de la Expresión Génica , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , FN-kappa B/genética , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patología , Osteogénesis/genética , Fenilendiaminas/farmacología , Ligando RANK/farmacología , Células RAW 264.7 , Receptores de Calcitonina/genética , Receptores de Calcitonina/metabolismo , Proteína Estafilocócica A/aislamiento & purificación , Staphylococcus aureus/química , Fosfatasa Ácida Tartratorresistente/genética , Fosfatasa Ácida Tartratorresistente/metabolismoRESUMEN
Objective To investigate the effect of Roux-en-Y gastric bypass surgery on renal gluconeogenesis, and to explore the mechanism of improving glucose control and insulin sensitivity in obese rats.Methods Rats were randomly divided into the obese group (n=30) consumed high-fat diet (HFD) and control group (NC group, n=8).Top 24 of animals fed HFD by change in body mass were subdivided into three groups: obese control group (OB group, n=8), obese under RYGB group (RYGB group, n=8) or sham-operation (sham group, n=8).Intraperitoneal glucose tolerance tests (IPGTT) were performed meanwhile the AUC of blood glucose concentration-time after surgery.Fasting glucose, insulin and lipid were measured respectively and HOMA-IR were calculated.The mRNA level and protein level of the key enzymes (G6P and PEPCK) of renal gluconeogenesis were examined with RT-PCR and Western blot respectively.Results Compared with OB group and Sham group, the body mass, lipid, blood glucose, insulin, HOMA-IR and AUG were significantly decreased (P<0.05), the expression of G6P and PEPCK mRNA and protein were significantly reduced(P<0.05) in RYGBgroup.Conclusions Roux-en-Y gastric bypass surgery can improve glucose control and insulin resistance, which may be related to the decreased level of mRNA, protein of G6P and PEPCK, reduced gluconeogenesis and glucose output in renal cortex.
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Dust storms in northern China strongly affect the living and health of people there and the dusts could travel a full circle of the globe in a short time. Historically, more frequent dust storms occurred during cool periods, particularly the Little Ice Age (LIA), generally attributed to the strengthened Siberian High. However, limited by chronological uncertainties in proxy records, this mechanism may not fully reveal the causes of dust storm frequency changes. Here we present a late Holocene dust record from the Qaidam Basin, where hydrological changes were previously reconstructed, and examine dust records from northern China, including the ones from historical documents. The records, being broadly consistent, indicate the onset of frequent dust storms at ~AD 1100. Further, peaked dust storm events occurred at episodes of high total solar irradiance or warm-dry conditions in source regions, superimposed on the high background of frequent dust storms within the cool LIA period. We thus suggest that besides strong wind activities, the centennial-scale dust storm events over the last 1000 years appear to be linked to the increased availability of dust source. With the anticipated global warming and deteriorating vegetation coverage, frequent occurrence of dust storms in northern China would be expected to persist.
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Long non-coding RNAs (lncRNAs) CCAT1 and HOTAIR have been shown to play an important regulatory role in cancer biology, and CCAT1 and HOTAIR are upregulated in several cancers, however, its value in the diagnosis of colorectal cancer (CRC) is unclear. Therefore, the aim of this study is to evaluate the clinical significance of plasma CCAT1 and HOTAIR as a biomarker in the screening of CRC. In our study, we found that the levels of HOTAIR (P < 0.05) and CCAT1 (P < 0.05) were significantly higher in plasma of CRC patients than that of the healthy control. Moreover, the levels of lincRNA-p21 (P < 0.05) were obviously decreased in plasma of CRC patients as compared to those of healthy control. There was highly correlated for CCAT1 (R = 0.752, mean differences = -0.06 ± 1.20), HOTAIR (R = 0.739, mean differences = -0.26 ± 0.76) and lincRNA-p21 (R = 0.848, mean differences = -0.41 ± 0.89) in plasma and serum. By receiver operating characteristic curve (ROC) analysis, plasma CCAT1 provided the higher diagnostic performance for detection of CRC (the area under the ROC curve (AUC), 0.836; P < 0.001; sensitivity, 75.7%; specificity, 85.3%). Moreover, CCAT1 combining with HOTAIR could provide a more effective diagnosis performance (AUC, 0.954, P < 0.001, sensitivity, 84.3%; specificity, 80.2%). Most importantly, this combination was effective to detect CRC at an early stage (85%). In conclusion, our results demonstrated that increased plasma HOTAIR and CCAT1 could be used as a predictive biomarker for CRC screening, and that combination of HOTAIR and CCAT1 had a higher positive diagnostic rate of CRC than HOTAIR or CCAT1 alone.
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Biomarcadores de Tumor/sangre , Carcinoma/sangre , Neoplasias Colorrectales/sangre , Detección Precoz del Cáncer , ARN Largo no Codificante/sangre , Área Bajo la Curva , Biomarcadores de Tumor/genética , Carcinoma/genética , Carcinoma/mortalidad , Carcinoma/patología , Estudios de Casos y Controles , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Detección Precoz del Cáncer/métodos , Humanos , Estimación de Kaplan-Meier , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , ARN Largo no Codificante/genética , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Regulación hacia ArribaRESUMEN
<p><b>OBJECTIVES</b>To study the clinical characteristics of hepatic failure with aspergillosis.</p><p><b>METHODS</b>The data of hepatic failure patients with fungal infection hospitalized in our hospital form January 1985 to June 2006 were collected. This research mainly focused on the clinical characteristics of the patients co-infected with aspergillosis.</p><p><b>RESULTS</b>The occurrence of aspergillosis was 20.5% (104 cases) among 507 hepatic failure patients with fungal infection. Compared with other fungal infection in hepatic failure patients, the effective rate of antifungal therapy and the improvement rate of underlying disease were worse in patients with aspergillus infection (36.5% vs 57.8%, P = 0.000; 26.0% vs 36.7%, P = 0.049). Aspergillus fumigatus was the most common species among 108 fungal species. The species next to Aspergillus fumigatus were Aspergillus niger and Aspergillus flavus. The mainly infected organ was lung and its clinical manifestation was atypical. Liver function could be improved with effective anti-fungus therapy.</p><p><b>CONCLUSIONS</b>Diagnosis and treatment of aspergillosis is difficult in hepatic failure patients co-infected with aspergillosis. Early and effective antifungal therapy is helpful to the recovery of liver function in the hepatic failure patients suspected with aspergillosis co-infection.</p>
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Humanos , Antifúngicos , Usos Terapéuticos , Aspergilosis , Diagnóstico , Quimioterapia , Aspergillus , Fallo Hepático , Diagnóstico , Quimioterapia , MicrobiologíaRESUMEN
<p><b>OBJECTIVE</b>To construct a eukaryotic expression vector for expressing hepatitis B virus (HBV) recombinant HBsAg-EGFP fusion protein and obtain a stable transfected Chang Liver cell line.</p><p><b>METHODS</b>The coding region of HBsAg gene of HBV was amplified by PCR and was digested by BamH I/EcoR I . This fragment was inserted into pEGFPN1 with T4 ligase and transformed E-coli TG1. The positive recombinant plasmid was selected, then the recombinant plasmid was transfected into Chang Liver cell by Lipofectamine 2000 cells containing stable transformants were selected by the ability of resistance to G418 and isolated with a limited dilution. The stable transfected cell line expressing high level HBsAg-EGFP fusion protein was obtained.</p><p><b>RESULTS</b>The eukaryotic expression vector named pEGFPN1-HBsAg was successfully constructed and the stable transfected Chang Liver cell line expressing pEGFPN1-HBsAg fusion protein was obtained.</p><p><b>CONCLUSION</b>The stable transfected Chang Liver cell line could express pEGFPN1-HBsAg fusion protein, could be used to screen the proteins differentially expressed in HBsAg expression Chang Liver cells, which brought some new clues for studying the potential molecular mechanism of HBsAg protein.</p>