Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis. Down‐regulation of miR‐195 has been observed in various types of cancers. However, the biological ...function of miR‐195 is still largely unknown. In this study we aimed to elucidate the pathophysiologic role of miR‐195. Our results showed that miR‐195 expression was significantly reduced in as high as 85.7% of hepatocellular carcinoma (HCC) tissues and in all of the five HCC cell lines examined. Moreover, introduction of miR‐195 dramatically suppressed the ability of HCC and colorectal carcinoma cells to form colonies in vitro and to develop tumors in nude mice. Furthermore, ectopic expression of miR‐195 blocked G1/S transition, whereas inhibition of miR‐195 promoted cell cycle progression. Subsequent investigation characterized multiple G1/S transition‐related molecules, including cyclin D1, CDK6, and E2F3, as direct targets of miR‐195. Silencing of cyclin D1, CDK6, or E2F3 phenocopied the effect of miR‐195, whereas overexpression of these proteins attenuated miR‐195‐induced G1 arrest. In addition, miR‐195 significantly repressed the phosphorylation of Rb as well as the transactivation of downstream target genes of E2F. These results imply that miR‐195 may block the G1/S transition by repressing Rb‐E2F signaling through targeting multiple molecules, including cyclin D1, CDK6, and E2F3. Conclusion: Our data highlight an important role of miR‐195 in cell cycle control and in the molecular etiology of HCC, and implicate the potential application of miR‐195 in cancer therapy. (HEPATOLOGY 2009.)
N-Heterocyclic carbene (NHC) functionalized MCM-41 was synthesized by reacting 1,3-bis-(4-allyl-2,6-diisopropylphenyl) imidazolium chloride with MCM-41 using 3-mercaptopropyltrimethoxysilane as ...silane coupling agent, and its CO2 adduct (designated as MCM-41-IPr-CO2) was further synthesized by the reaction with CO2. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was used to investigate the reversible CO2 capture-release ability of MCM-41-NHC. MCM-41-IPr-CO2 adduct proved to be an efficient heterogeneous catalyst for the cycloaddition of CO2 to epoxides or aziridines with excellent regioselectivity under mild conditions. Moreover, the catalyst could be recovered easily through a simple filtration process and reused multiple times without obvious loss in activity, owing to CO2 as protective group for effectively stabilizing the NHC anchored on MCM-41.
Aims
To determine psychological symptoms of patients with mild symptoms of coronavirus disease 2019 in China and to explore the influencing factors.
Design
A cross‐sectional study.
Methods
A ...convenience sample of 296 mild coronavirus disease 2019 patients were recruited from a Fangcang hospital in Wuhan, Hubei Province, from 3–5 March, 2020. Participants were assessed using a sociodemographic and clinical characteristics questionnaire, and Symptom Check List 90. The binary logistic regression was utilized to explore the influencing factors of psychological symptoms of patients with mild symptoms of coronavirus disease 2019.
Results
In total, 296 of 299 patients with mild symptoms of coronavirus disease 2019 participated in the study (response rate: 99.0%). The findings revealed that 12.8% patients with mild symptoms have mental health problems; the most common psychological symptoms are phobic anxiety (58.4%), paranoid ideation (50.7%) and psychoticism (40.2%). Female patients OR = 3.587, 95% CI (1.694–7.598) and those having physical symptoms currently OR = 2.813, 95% CI (1.210–6.539) are at higher risk, while those in the middle duration of hospitalization OR = 0.278, 95% CI (0.121–0.639) protect against mental‐health problems.
Conclusions
The minority of patients with mild symptoms of coronavirus disease 2019 were still suffering from psychological symptoms. Healthcare providers are recommended to pay particular attention to screening these high‐risk groups (women, those in the initial stages of hospitalization and those with physical symptoms currently) and implement targeted psychological care as required.
Impact
This study found that most patients of coronavirus disease 2019 in Fangcang hospital exhibited normal mental health at par with the general Chinese norm and the minority of them were suffering from psychological symptoms. The findings can provide a reference for healthcare providers to screen high‐risk psychological symptoms groups and implement targeted psychological intervention for patients with coronavirus disease 2019.
摘要
目的
了解中国新冠病毒肺炎轻度症状患者的心理症状, 并探讨影响因素。
设计
一项横截面研究。
方法
2020年3月3日至3月5日, 在湖北省武汉市方仓医院招募296例新冠病毒肺炎轻度症状患者作为便利样本。采用社会人口学和临床特征调查问卷以及症状自评量表90对参与者进行评估。利用二元逻辑回归探讨了新冠病毒肺炎患者心理症状的影响因素。
结果
在299例新冠病毒肺炎轻度症状患者中, 共有296例参与研究 (有效率: 99.0%) 。研究结果显示, 12.8%的轻度症状患者存在心理健康问题; 最常见的心理症状是恐惧焦虑 (58.4%) 、偏执(50.7%) 和精神质 (40.2%) 。女性患者【OR=3.587,95%CI(1.694‐7.598) 】和目前有体症的患者【OR=2.813,95%CI(1.210‐6.539) 】风险较高, 而住院中期的患者【OR=0.278,95%CI(0.121‐0.639) 】可以预防心理健康问题。
结论
在新冠病毒肺炎病症状较轻的患者中, 少数患者仍有心理症状。建议医疗服务提供者特别注意筛查这些高危人群 (女性、住院初期和目前有身体症状的人群) , 并根据需要实施针对性的心理护理。
影响
本研究发现, 方仓医院新冠病毒肺炎病患者大多表现为心理健康正常, 与中国一般常态持平, 少数患者存在心理症状。该研究结果可为医疗服务提供者筛选高危心理症状群体并对新冠病毒肺炎患者实施针对性的心理干预提供参考。
Breast cancer is the leading cause of cancer death among females, with tumor metastasis being primarily responsible for breast cancer-associated mortality. Current literatures have shown that ...microRNAs (miRNAs) are implicated in tumor metastasis. In this study, we found that the expression of miR-720 was significantly downregulated in primary breast cancer, with greater downregulation in metastatic tumors. Statistical analysis of 105 cases of primary human breast cancer demonstrated that decreased expression of miR-720 was correlated with lymph node metastasis. Furthermore, reexpression of miR-720 in breast cancer cells remarkably inhibited cell invasiveness and migration both in vitro and in vivo. Mechanistically, downregulation of TWIST1, a promoter of metastasis that was identified as a direct functional target of miR-720, was attributed to the inhibition of metastasis. Consistent with the reduced TWIST1 levels in breast cancer, reexpression of miR-720 upregulated epithelial markers (E-cadherin and β-catenin) and downregulated mesenchymal markers (N-cadherin, fibronectin, vimentin and matrix metalloproteinase-2). Expression of miR-720 was inversely associated with TWIST1 in human breast cancer tissues. Knockdown of TWIST1 expression by small interfering RNA exhibited similar effects to reintroduction of miR-720, whereas overexpression of TWIST1 (without the 3'-untranslated region) abrogated miR-720-mediated metastasis inhibition. Collectively, our data indicate that miR-720 is frequently decreased in breast cancer and manifests antimetastatic activity by downregulating TWIST1, presenting a novel mechanism of miRNA-mediated regulation of tumor metastasis.
Triple-negative breast cancer (TNBC) is associated with an increased risk of metastasis and a poor prognosis. The invasive ability of TNBC relies on actin reorganization and is regulated by histone ...deacetylase 6 (HDAC6). The present study aimed to examine the effect of MPT0G211, a novel HDAC6 inhibitor, on cell migration and microtubule association in both in vitro and in vivo models of TNBC. Here MPT0G211 more selectively and potently targeted and inhibited HDAC6, compared with tubastatin A, another selective HDAC6 inhibitor. In vitro, MPT0G211 decreased the migration of the TNBC cell line MDA-MB-231, particularly when administered together with paclitaxel, and increased heat shock protein 90 (Hsp90) acetylation, leading to the dissociation of Hsp90 from aurora-A and proteasomal degradation. Furthermore, MPT0G211 significantly disrupted F-actin polymerization by increasing cortactin acetylation and downregulating slingshot protein phosphatase 1 (SSH1) and active cofilin expression. In vivo, MPT0G211 treatment significantly ameliorated TNBC metastasis. In conclusion, our results demonstrate that MPT0G211 reduces TNBC cell motility by promoting cortactin acetylation and aurora-A degradation, and inhibiting the cofilin–F-actin pathway via HDAC6 activity attenuation. MPT0G211 therefore demonstrates therapeutic potential for invasive TNBC.
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•MPT0G211 more selectively and potently inhibited HDAC6 activity than TubA.•MPT0G211 decreased the migration of the triple-negative breast cancer cells.•MPT0G211 disrupted F-actin polymerization by HDAC6 activity inhibition.•In vivo, MPT0G211 treatment significantly ameliorated TNBC metastasis.
Histone deacetylase (HDAC) inhibitors have been considered as an attractive strategy to reverse aberrant epigenetic changes associated with cancer treatments. The use of HDAC inhibitors in various ...cancer types has continued to develop for decades, bringing several novel HDAC inhibitors successfully into clinical trials. The combination use of HDAC inhibitors with other agents have also been developed and have demonstrated superior efficacy compared to that of monotherapy in recent studies. Hence, development of new anticancer treatment and therapeutic regimen is necessary.
This review summarizes a comprehensive review of the patent literature from 2020 to 2022 including HDAC inhibitors and their use as anticancer agents (searched from European Patent Office, 2020-2022). The approved and developing HDAC inhibitors are described. It also provides perspectives on the challenges and future opportunities.
Although hundreds of clinical trials of HDAC inhibitors are still going on, the application for HDAC inhibitors has been limited at present . Not only in the anticancer treatment, but also non-oncology disease therapies are being investigated eagerly. Recently, applications of HDAC inhibitors in non-oncology diseases have also been revealed and proceeded to clinical trials. New indications for HDAC inhibitors are needed urgently in the future.
The comparisons of molecular characterization and antibiotic resistance of Klebsiella pneumoniae (KP) isolates from humans and other animal hosts are not well studied. Our goal was to compare the ...molecular epidemiology of KP strains that were isolated from urban rodents, shrews, and healthy people.
K. pneumoniae (KP) isolates were isolated from fecal samples of rodents, shrews and healthy adults in 2015 in southern China. In total, 465 fecal samples were collected, of which 85 from rodents, 105 from shrews, and 275 from healthy adults. Antimicrobial susceptibility and production of extended-spectrum β-lactamases (ESBL) of the isolates were tested. PCR-based methods were used to detect specific genes, including ESBL genes (bla
, bla
and bla
) in ESBL-producing isolates, capsular serotypes (K1, K2, K5, K20, K54, and K57) in hypervirulent KPs (hvKPs), and virulence genes (magA, wcaG, rmpA, uge, kfu, and aerobactin) in hvKP isolates. Multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to exclude the homology of these isolates. The carriage rate of KP in urban rodents and shrews (78.42%) was higher than that in healthy adults (66.18%) (χ
= 8.206, P = 0.004). The prevalence rates of ESBL-producing isolates among rodents, shrews, and humans were 7.94, 12.79, and 17.03%, respectively. The positive rates of CTX-M, TEM and SHV types in ESBL-producing isolates were 29.79, 27.66, and 17.02%, respectively. Serotype K1, K5, K20, and K57 were detected in both small mammals and humans. PFGE typing revealed thirty-six clusters. PFGE cluster A was clustered by samples of shrews and healthy adult, with a similarity of 88.4%. MLST typing revealed thirty-eight types. ST23 and ST35 were detected in samples of shrews and healthy adults. ST37 was detected in samples of 2 rodents and a healthy adult.
Overlapping serotypes of hvKP were observed in both the animals and humans. The same PFGE or MLST types were also found in isolates derived humans, rodents and shrews. Therefore, urban rodents and shrews might play a certain role in the transmission of drug-resistant and hypervirulent KP.
Tailored by flame-retardant, localized high-concentration electrolyte with relatively weakened anion-involved configuration and non-solvating fluorinated ether, the robust solid electrolyte ...interphase featuring well-balanced inorganic/organic components with lower resistance against K-ion transport is constructed, significantly enhancing long-term cyclic stability of K-storage in graphite.
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Although graphite anodes operated with representative de/intercalation patterns at low potentials are considered highly desirable for K-ion batteries, the severe capacity fading caused by consecutive reduction reactions on the aggressively reactive surface is inevitable given the scarcity of effective protecting layers. Herein, by introducing a flame-retardant localized high-concentration electrolyte with retentive solvation configuration and relatively weakened anion-coordination and non-solvating fluorinated ether, the rational solid electrolyte interphase characterized by well-balanced inorganic/organic components is tailored in situ. This effectively prevented solvents from excessively decomposing and simultaneously improved the resistance against K-ion transport. Consequently, the graphite anode retained a prolonged cycling capability of up to 1400cycles (245 mA h g−1, remaining above 12mon) with an excellent capacity retention of as high as 92.4%. This is superior to those of conventional and high-concentration electrolytes. Thus, the optimized electrolyte with moderate salt concentration is perfectly compatible with graphite, providing a potential application prospect for K-storage evolution.
Long non-coding RNAs (lncRNAs) have been identified to be critical mediators in various tumors associated with cancer progression. Long non-coding RNA activated by TGF-β (lncRNA-ATB) is a stimulator ...of epithelial-mesenchymal transition (EMT) and serves as a novel prognostic biomarker for hepatocellular carcinoma. However, the biological role and clinical significance of lncRNA-ATB in human prostate cancer have yet to be fully elucidated. The present study was designed to explore the expression of lncRNA-ATB in human prostate cancer patients and the role of lncRNA-ATB in prostate cancer cells. We showed that lncRNA-ATB expression was significantly upregulated in tumor tissues in patients with prostate cancer in comparison with adjacent non-tumor tissues. Further analysis indicted that high lncRNA-ATB expression may be an independent prognostic factor for biochemical recurrence (BCR)-free survival in prostate cancer patients. Overexpression of lncRNA-ATB promoted, and knockdown of lncRNA-ATB inhibited the growth of prostate cancer cells via regulations of cell cycle regulatory protein expression levels. In addition, lncRNA-ATB stimulated epithelial-mesenchymal transition (EMT) associated with ZEB1 and ZNF217 expression levels via ERK and PI3K/AKT signaling pathways. These results indicated that lncRNA-ATB may be considered as a new predictor in the clinical prognosis of patients with prostate cancer. Overexpression of lncRNA-ATB exerts mitogenic and EMT effects of prostate cancer via activation of ERK and PI3K/AKT signaling pathways.
Abstract The NASICON cathode, Na 3 V 2 (PO 4 ) 3 , has garnered significant attention due to its robust framework with fast Na + migration. To expand its application scenarios by diversified ...electronic reaction, the substitution of vanadium with cost‐effective and abundant redox elements is a special research topic. Nevertheless, in terms of reducing toxicity, increasing Na content and widening voltage range, the V 4+/5+ redox couple in Na 4 FeV(PO 4 ) 3 often accompanies asymmetric and irreversible electrochemical reactions that pose a dilemma for capacity and structural stability, especially at high currents. Herein, in this work, Na 4 FeV 1/3 Ti 2/3 (PO 4 ) 3 (NFVT) has achieved highly reactive of multiple electron transfer (Ti 2+/3+ , Fe 2+ / 3+ , and V 3+/4+ / 5+ ) by utilizing the redox reaction with quasi‐monophase behavior, and it can reserve great capacity retention after 3,000 cycles. More competitively, its boosting kinetics makes the fast‐charging characteristic, just requiring only 3.63 min to reach 80% state of charge at 2 C. The rapid ion/electron transport dynamics can achieve the decay of only 0.043% per cycle by unlocking the quasi‐monophase behavior in the framework of NFVT full cells. The present study provides a fresh perspective on designing cathode materials with fast‐charging capabilities for sodium‐ion batteries.
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