The epigenetic dysregulation and hypoxia are two important factors that drive tumor malignancy, and N6‐methyladenosine (m6A) in mRNA is involved in the regulation of gene expression. Herein, a ...nanocatalyst OsSx‐PEG (PEG = poly(ethylene glycol)) nanoparticles (NPs) as O2 modulator is developed to improve tumor hypoxia. OsSx‐PEG NPs can significantly downregulate genes involved in hypoxia pathway. Interestingly, OsSx‐PEG NPs elevate RNA m6A methylation levels to cause the m6A‐dependent mRNA degradation of the hypoxia‐related genes. Moreover, OsSx‐PEG NPs can regulate the expression of RNA m6A methyltransferases and demethylases. Finally, DOX@OsSx‐PEG (DOX = doxorubicin; utilized as a model drug) NPs modulate tumor hypoxia and regulate mRNA m6A methylation of hypoxia‐related genes in vivo. As the first report about relationship between catalytic nanomaterials and RNA modifications, the research opens a new avenue for unveiling the underlying action mechanisms of hypoxia‐modulating nanomaterials and shows potential of regulating RNA modification to overcome chemoresistance.
Modified OsSx catalytic nanoparticles (NPs) are developed as drug carriers for combined chemo‐photothermal therapy with multi‐model imaging. OsSx‐PEG NPs can catalyze decomposition of H2O2 to produce O2 to modulate hypoxia and enhance drug sensitivity. Moreover, OsSx‐PEG NPs can cause mRNA degradation of hypoxia‐related genes by regulating RNA m6A methylation levels.
Core decompression (CD) is an important method for the treatment of osteonecrosis of the femoral head (ONFH). Few articles investigate the influence of core decompression on outcomes of ONFH. This ...study was carried out to observe the safety and effectiveness of core decompression in the treatment of ONFH.
A comprehensive literature search of databases including PubMed, Embase, and Cochrane Library was performed to collect the related studies. The medical subject headings used were "femur head necrosis" and "Core decompression." The relevant words in title or abstract included but not limited to "Osteonecrosis of the Femoral Head," "femoral head necrosis," "avascular necrosis of femoral head," and "ischemic necrosis of femoral head." The methodological index for nonrandomized studies was adopted for assessing the studies included in this review.
Thirty-two studies included 1865 patients (2441 hips). Twenty-one studies (1301 hips) using Ficat staging standard, 7 studies (338hips) using Association Research Circulation Osseous (ARCO) staging standard, and University of Pennsylvania system for staging avascular necrosis (UPSS) staging criteria for 4 studies (802 hips). All the studies recorded the treatment, 22 studies (1379 hips) were treated with core decompression (CD) alone, and 7 studies (565 hips) were treated with core decompression combined with autologous bone (CD Autologous bone). Nine subjects (497 hips) were treated with core decompression combined with autologous bone marrow (CD Marrow). Twenty-seven studies (2120 hips) documented the number of conversion to total hip replacement (THA), and 26 studies (1752hips) documented the number of radiographic progression (RP). Twenty-one studies recorded the types of complications and the number of cases, a total of 69 cases. The random-effect model was used for meta-analysis, and the results showed that the overall success rate was 65%. The rate of success showed significant difference on the outcomes of different stages. The rate of success, conversion to THA, and radiographic progression showed significant difference on the outcomes of ONFH using different treatments.
Core decompression is an effective and safe method of treating ONFH. The combined use of autologous bone or bone marrow can increase the success rate. For advanced femoral head necrosis, the use of CD should be cautious. High-quality randomized controlled trials and prospective studies will be necessary to clarify the effects of different etiology factors, treatments, and postoperative rehabilitation. Until then, the surgeon can choose core decompression to treat ONFH depending on the patient's condition.
I Meta-analysis.
The increasing volume of sewage sludge from wastewater treatment facilities is becoming a prominent concern globally. The disposal of this sludge is particularly challenging and poses severe ...environmental hazards due to the high content of organic, toxic and heavy metal pollutants among its constituents. This study presents a simple review of four sewage to energy recovery routes (anaerobic digestion, combustion, pyrolysis and gasification) with emphasis on recent developments in research, as well as benefits and limitations of the technology for ensuring cost and environmentally viable sewage to energy pathway. This study focusses on the review of various commercially viable sludge conversion processes and technologies used for energy recovery from sewage sludge. This was done via in-depth process descriptions gathered from literatures and simplified schematic depiction of such energy recovery processes when utilised for sludge. Specifically, the impact of fuel properties and its effect on the recovery process were discussed to indicate the current challenges and recent scientific research undertaken to resolve these challenges and improve the operational, environmental and cost competitiveness of these technologies.
Many cancers including head and neck squamous cell carcinoma (HNSCC) are characterized by a metabolic rewiring with increased glucose uptake and lactate production, termed as aerobic glycolysis. ...Targeting aerobic glycolysis presents a promising strategy for cancer therapy. This study investigates the therapeutic potential of glycolysis blockage by targeting phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) in HNSCC.
1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15) was used as a selective antagonist of PFKFB3. Glycolytic flux was determined by measuring glucose uptake, lactate production and ATP yield. PFKFB3 expression was examined using HNSCC tissue arrays. Cell proliferation, apoptosis and motility were analysed. HNSCC xenograft mouse model and metastasis mouse model were established to examine the therapeutic efficacy of PFK15 in vivo.
HNSCC showed an increased PFKFB3 expression compared with adjacent mucosal tissues (P < 0.01). Targeting PFKFB3 via PFK15 significantly reduced the glucose uptake, lactate production and ATP generation in HNSCC cell lines. PFK15 suppressed cell proliferation, halted cell cycle progression and induced cell apoptosis. The invadopodia of HNSCC cells was markedly reduced after PFK15 treatment, thereby impairing cell motility and extracellular matrix degradation ability. The in vivo data from the xenograft mice models proved that PFK15 administration suppressed the tumor growth. And the results from the metastatic mice models showed administration of PFK15 alleviated the lung metastasis of HNSCC and extended the life expectancy of mice.
The pharmacological inhibition of PFKFB3 via PFK15 suppressed tumor growth and alleviated metastasis in HNSCC, offering a promising strategy for cancer therapy.
We have proposed a facile and cheap cancer therapeutic strategy by in-cell synthesizing theranostic Zn Schiff base complexes with nuclear targeting and DNA damaging capability. The in-cell synthesis ...can be traced
via
a green-to-blue fluorescence shift, and the subsequent cytoplasm-to-nucleus translocation realizes cancer-specific therapy both
in vitro
and
in vivo
.
A facile and cheap strategy based on visualized in-cell synthesis of theranostic Zn Schiff base complexes realizes cancer-specific therapy.
•On day 14 after the admission, no viral load was detected in arbidol group.•44.1% of patients in lopinavir/ritonavir group had positive RNA test on day 14.•Patients in the arbidol group had a ...shorter duration of positive RNA test.•No apparent side effects were found in both groups.•Arbidol monotherapy may be superior to lopinavir/ritonavir in treating COVID-19.
Lopinavir/ritonavir and arbidol have been previously used to treat acute respiratory syndrome- coronavirus 2 (SARS-CoV-2) replication in clinical practice; nevertheless, their effectiveness remains controversial. In this study, we evaluated the antiviral effects and safety of lopinavir/ritonavir and arbidol in patients with the 2019-nCoV disease (COVID-19). Fifty patients with laboratory-confirmed COVID-19 were divided into two groups: including lopinavir/ritonavir group (34 cases) and arbidol group (16 cases). Lopinavir/ritonavir group received 400 mg/100mg of Lopinavir/ritonavir, twice a day for a week, while the arbidol group was given 0.2 g arbidol, three times a day. Data from these patients were retrospectively analyzed. The cycle threshold values of open reading frame 1ab and nucleocapsid genes by RT-PCR assay were monitored during antiviral therapy. None of the patients developed severe pneumonia or ARDS. There was no difference in fever duration between the two groups (P=0.61). On day 14 after the admission, no viral load was detected in arbidol group, but the viral load was found in 15(44.1%) patients treated with lopinavir/ritonavir. Patients in the arbidol group had a shorter duration of positive RNA test compared to those in the lopinavir/ritonavir group (P<0.01). Moreover, no apparent side effects were found in both groups. In conclusion, our data indicate that arbidol monotherapy may be superior to lopinavir/ritonavir in treating COVID-19.
Maotai‐flavor liquor is one of the three basic traditional Chinese baijiu and is also the most famous baijiu in the world. Guizhou Maotai baijiu is the representative of Maotai‐flavor liquor, which ...has a long history of culture and is prepared using unique brewing methods. However, the main flavor of Maotai‐flavor liquor as well as the mechanism by which its aroma is produced is unclear. In this review, the Da‐qu production and fermentation processes for Maotai‐flavor liquor are briefly described along with the flavoring constituents of Maotai‐flavor liquor that have been recently reported. In addition, the volatile compounds and the aroma derived from Maotai‐flavor liquor are discussed. Finally, the microorganisms for the high‐temperature Daqu and fermentation processes of Maotai‐flavor liquor are discussed.
Practical Application
Maotai is one of the most famous baijiu in China and the most valuable in the market. However, it is unclear what is the key flavor of Maotai and what microbial metabolism is produced. So, if we can figure out the key flavor substances of Maotai baijiu, we can use the various technology to explore the microbes that produce this flavor to understand the mechanism of the production of Maotai. This will not only achieve breakthroughs in academic value, but also bring higher value to Maotai. On this basis, we can brew Maotai baijiu with better quality according to the fermentation mechanism of Maotai.
Lack of social support is a known predictor of the prognosis after acute myocardial infarction (AMI). Although as a common factor associated with social support, there are limited data on long-term ...prognostic impact of living status in young and middle-aged patients with AMI.
We analyzed data from the China Acute Myocardial Infarction (CAMI) Registry, consecutive AMI young and middle-aged patients admitted at 108 hospitals in China between January 2013 and September 2014 were included. Eligible patients were assigned to living alone and not living alone groups based on their living status. The primary endpoint was 2-year all-cause mortality. The secondary endpoints included in-hospital mortality and 2-year major adverse cardiac and cerebrovascular events (MACCEs; a composite of all-cause mortality, MI, or stroke). Multilevel logistic and multilevel Cox regression models were used to evaluate the effect of living status on short-term and long-term outcomes.
A total of 8307 consecutive AMI young and middle-aged patients were included, 192 (2.3%) patients were living alone. Of the analyzed patients, living alone was associated with 2-year all-cause mortality and MACCEs among all analyzed patients after multivariate adjustment (adjusted hazard ratio HR = 2.171 1.210-3.895, P = 0.009; adjusted HR = 2.169 1.395-3.370, P = 0.001), but not with poorer in-hospital mortality.
The analysis suggested that living alone was associated with both 2-year all-cause mortality and MACCEs in AMI young and middle-aged patients but did not show an extra effect on the in-hospital mortality after covariate adjustment.
Trial registration number: NCT01874691; Registered 31 October 2012.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ambient backscatter communication (AmBC) enables a passive backscatter device to transmit information to a reader using ambient RF signals, and has emerged as a promising solution to green ...Internet-of-Things (IoT). Conventional AmBC receivers are interested in recovering the information from the ambient backscatter device (A-BD) only. In this paper, we propose a cooperative AmBC (CABC) system in which the reader recovers information not only from the A-BD, but also from the RF source. We first establish the system model for the CABC system from spread spectrum and spectrum sharing perspectives. Then, for flat fading channels, we derive the optimal maximum-likelihood (ML) detector, suboptimal linear detectors as well as successive interference-cancellation (SIC) based detectors. For frequency-selective fading channels, the system model for the CABC system over ambient orthogonal frequency division multiplexing carriers is proposed, upon which a low-complexity optimal ML detector is derived. For both kinds of channels, the bit-error-rate expressions for the proposed detectors are derived in closed forms. Finally, extensive numerical results have shown that, when the A-BD signal and the RF-source signal have equal symbol period, the proposed SIC-based detectors can achieve near-ML detection performance for typical application scenarios, and when the A-BD symbol period is longer than the RF-source symbol period, the existence of backscattered signal in the CABC system can enhance the ML detection performance of the RF-source signal, thanks to the beneficial effect of the backscatter link when the A-BD transmits at a lower rate than the RF source.