Publications by authors named "Miao Zhang"

1,003 Publications

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The Role of Long Non-coding RNA, Nuclear Enriched Abundant Transcript 1 (NEAT1) in Cancer and Other Pathologies.

Biochem Genet 2021 Oct 24. Epub 2021 Oct 24.

School of Kinesiology, Shanghai University of Sport, Shanghai, 200438, China.

Nuclear enriched abundant transcript 1 (NEAT1), consisting of two kinds of lncRNAs of 3.7 kB NEAT1-1 and 23 kB NEAT1-2, can be highly expressed in organs and tissues such as the ovary, prostate, colon, and pancreas, and is involved in paraspeckle formation and mRNA editing and gene expression. Therefore, NEAT1 is a potential biomarker for the treatment of a variety of diseases, which may be caused by two factors (isoforms of NEAT1 and NEAT1 sponging miRNA as ceRNA). However, there is still much confusion about the mechanism and downstream effector between the abnormal expression of NEAT1 and various diseases. This review summarizes recent research progress on NEAT1 in cancer and other pathologies and provides a more reliable theoretical basis for the treatment of related diseases.
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http://dx.doi.org/10.1007/s10528-021-10138-8DOI Listing
October 2021

Systematic Construction and Validation of a Prognostic Model for Hepatocellular Carcinoma Based on Immune-Related Genes.

Front Cell Dev Biol 2021 4;9:700553. Epub 2021 Oct 4.

State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China.

Hepatocellular carcinoma (HCC), a highly aggressive tumor, has high incidence and mortality rates. Recently, immunotherapies have been shown to be a promising treatment in HCC. The results of either the CheckMate-040 or IMbrave 150 trials demonstrate the importance of immunotherapy in the systemic treatment of liver cancer. Thus, in this study, we tried to establish a reliable prognostic model for liver cancer based on immune-related genes (IRGs) and to provide a new insight for immunotherapy of HCC. In this study, we used four datasets that incorporated 851 HCC samples, including 340 samples with complete clinical information from the cancer genome atlas (TCGA) database, to establish an effective model for predicting the prognosis of HCC patients based on the differential expression of IRGs and validated the prognostic model using the data from International Cancer Genome Consortium (ICGC). The top 6 characteristic IRGs identified by protein-protein interaction (PPI) network analysis, MMP9, FOS, CAT, ESR1, ANGPTL3, and KLKB1, were selected for further study. In addition, we assessed the correlations of the six characteristic IRGs with the tumor immune microenvironment, clinical stage, and sensitivity to anti-cancer drugs. We also explored whether the differential expression of the characteristic IRGs was specific to HCC or present in pan-cancer. The expression levels of the six characteristic IRGs were significantly different between most tumor tissues and adjacent normal tissues. In addition, these characteristic IRGs showed a strong association with immune cell infiltration in HCC patients. We found that MMP9 and ESR1 were independent prognostic factors for HCC, while CAT, ESR1, and KLKB1 were associated with the clinical stage. We collected HCC paraffin sections from 24 patients from Xijing hospital to identify the differential expression of the five genes (MMP9, ESR1, CAT, FOS, and KLKB1). Finally, the results of decision curve analysis (DCA) and nomogram revealed that our models provided a prognostic benefit for most HCC patients and the predicted overall survival (OS) was consistent with the actual OS. In conclusion, we systemically constructed a novel prognostic model that provides new insights into HCC.
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http://dx.doi.org/10.3389/fcell.2021.700553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520962PMC
October 2021

Integrating Intrinsic Radiosensitivity and Immune Status for Predicting Benefits of Radiotherapy in Head and Neck Squamous Cell Carcinoma.

Med Sci Monit 2021 Oct 21;27:e932126. Epub 2021 Oct 21.

Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).

BACKGROUND HNSCC (head and neck squamous cell carcinoma) is a heterogeneous disease for which radiotherapy is a main treatment. As intrinsic radiosensitivity and immune status affect the initial and effective stage of the radiation-induced cancer immunity cycle, respectively, it is important to consider both of them when we select patients who can benefit from radiotherapy. MATERIAL AND METHODS Our study included all HNSCC patients with complete survival and radiotherapy information in TCGA database. Patients were divided into RS (radiosensitive), RR (radioresistant), immune, and non-immune groups according to their RSI (radiosensitivity index) and immune score calculated by the ESTIMATE algorithm. Survival analysis was performed to compare OS (overall survival) between patients receiving and not receiving radiotherapy. GO and KEGG pathway enrichment analysis was performed for functional analysis. Univariate Cox and ridge regression analysis were performed to construct a predictive gene signature based on the combined stratification. RESULTS Only patients in the RS-immune group could benefit from radiotherapy, and the survival analysis results remained consistent after we performed propensity score matching between patients receiving and not receiving radiotherapy. The differentially expressed genes between the RS-immune and non-RS-immune groups were mainly enriched in pathways related to immune process. The 3-gene signature we built exhibited predictive value in training and validation cohorts when treated as a binary or continuous variable. CONCLUSIONS The combined stratification of intrinsic radiosensitivity and immune status was superior to considering intrinsic radiosensitivity or immune status alone and could be used in preclinical evaluation to select patients or to decide whether radiotherapy sensitizers and immunotherapy should be used at the same time.
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http://dx.doi.org/10.12659/MSM.932126DOI Listing
October 2021

Functional implication of heat shock protein 70/90 and tubulin in cold stress of Dermacentor silvarum.

Parasit Vectors 2021 Oct 19;14(1):542. Epub 2021 Oct 19.

Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, College of Life Sciences, Hebei Normal University, Shijiazhuang, 050024, China.

Background: The tick Dermacentor silvarum Olenev (Acari: Ixodidae) is a vital vector tick species mainly distributed in the north of China and overwinters in the unfed adult stage. The knowledge of the mechanism that underlies its molecular adaptation against cold is limited. In the present study, genes of hsp70 and hsp90 cDNA, named Dshsp70 and Dshsp90, and tubulin were cloned and characterized from D. silvarum, and their functions in cold stress were further evaluated.

Methods: The genome of the heat shock proteins and tubulin of D. silvarum were sequenced and analyzed using bioinformatics methods. Each group of 20 ticks were injected in triplicate with Dshsp90-, Dshsp70-, and tubulin-derived dsRNA, whereas the control group was injected with GFP dsRNA. Then, the total RNA was extracted and cDNA was synthesized and subjected to RT-qPCR. After the confirmation of knockdown, the ticks were incubated for 24 h and were exposed to - 20 °C lethal temperature (LT50), and then the mortality was calculated.

Results: Results indicated that Dshsp70 and Dshsp90 contained an open reading frame of 345 and 2190 nucleotides that encoded 114 and 729 amino acid residues, respectively. The transcript Dshsp70 showed 90% similarity with that identified from Dermacentor variabilis, whereas Dshsp90 showed 85% similarity with that identified from Ixodes scapularis. Multiple sequence alignment indicates that the deduced amino acid sequences of D. silvarum Hsp90, Hsp70, and tubulin show very high sequence identity to their corresponding sequences in other species. Hsp90 and Hsp70 display highly conserved and signature amino acid sequences with well-conserved MEEVD motif at the C-terminal in Hsp90 and a variable C-terminal region with a V/IEEVD-motif in Hsp70 that bind to numerous co-chaperones. RNA interference revealed that the mortality of D. silvarum was significantly increased after injection of dsRNA of Dshsp70 (P = 0.0298) and tubulin (P = 0.0448), whereas no significant increases were observed after the interference of Dshsp90 (P = 0.0709).

Conclusions: The above results suggested that Dshsp70 and tubulin play an essential role in the low-temperature adaptation of ticks. The results of this study can contribute to the understanding of the survival and acclimatization of overwintering ticks.
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http://dx.doi.org/10.1186/s13071-021-05056-yDOI Listing
October 2021

Longitudinal Changes of Sensorimotor Resting-State Functional Connectivity Differentiate between Patients with Thalamic Infarction and Pontine Infarction.

Neural Plast 2021 8;2021:7031178. Epub 2021 Oct 8.

Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

e. We investigated the disparate influence of lesion location on functional damage and reorganization of the sensorimotor brain network in patients with thalamic infarction and pontine infarction. . Fourteen patients with unilateral infarction of the thalamus and 14 patients with unilateral infarction of the pons underwent longitudinal fMRI measurements and motor functional assessment five times during a 6-month period (<7 days, at 2 weeks, 1 month, 3 months, and 6 months after stroke onset). Twenty-five age- and sex-matched controls underwent MRI examination across five consecutive time points in 6 months. Functional images from patients with left hemisphere lesions were first flipped from the left to the right side. The voxel-wise connectivity analyses between the reference time course of each ROI (the contralateral dorsal lateral putamen (dl-putamen), pons, ventral anterior (VA), and ventral lateral (VL) nuclei of the thalamus) and the time course of each voxel in the sensorimotor area were performed for all five measurements. One-way ANOVA was used to identify between-group differences in functional connectivity (FC) at baseline stage (<7 days after stroke onset), with infarction volume included as a nuisance variable. The family-wise error (FWE) method was used to account for multiple comparison issues using SPM software. Post hoc repeated-measure ANOVA was applied to examine longitudinal FC reorganization. . At baseline stage, significant differences were detected between the contralateral VA and ipsilateral postcentral gyrus (cl_VA-ip_postcentral), contralateral VL and ipsilateral precentral gyrus (cl_VL-ip_precentral). Repeated measures ANOVA revealed that the FC change of cl_VA-ip_postcentral differ significantly among the three groups over time. The significant changes of FC between cl_VA and ip_postcentral at different time points in the thalamic infarction group showed that compared with 7 days after stroke onset, there was significantly increased FC of cl_VA-ip_postcentral at 1 month, 3 months, and 6 months after stroke onset. . The different patterns of sensorimotor functional damage and reorganization in patients with pontine infarction and thalamic infarction may provide insights into the neural mechanisms underlying functional recovery after stroke.
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http://dx.doi.org/10.1155/2021/7031178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519702PMC
October 2021

Multiple osteolytic primary peripheral T-cell bone lymphoma: the first case report.

J Int Med Res 2021 Oct;49(10):3000605211052229

Department of Hematology, Fuyang People's Hospital (The Affiliated Fuyang People's Hospital of Anhui Medical University), Fuyang City, Anhui Province, China.

Peripheral T-cell lymphoma accounts for about 10% of all cases of non-Hodgkin's lymphoma. However, less than 5% of patients with non-Hodgkin's lymphoma present with hypercalcaemia as the initial symptom, and less than 1% present with primary bone lesions. We herein describe a 76-year-old Chinese man who was diagnosed with primary bone adult T-cell lymphoma with extensive osteolysis, including bone loss in the radius, as the initial manifestation. He had developed severe generalised bone pain and an inability to raise his arms. X-ray examination revealed osteolytic destruction of the forearm with loss of the radial diaphysis. The patient was diagnosed with peripheral T-cell lymphoma based on his immunohistochemical results. He began treatment with the CHOPE chemotherapy regimen, which resulted in significant improvement of his bone pain.
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http://dx.doi.org/10.1177/03000605211052229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524712PMC
October 2021

Functional Mechanism of Antimicrobial Peptide Bomidin and Its Safety for Macrobrachium rosenbergii.

Probiotics Antimicrob Proteins 2021 Oct 12. Epub 2021 Oct 12.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

Macrobrachium rosenbergii is an economically important source of crustacean seafood worldwide. Vibrio parahaemolyticus is an important aquatic pathogen that causes epidemics of acute hepatopancreatic necrosis in shrimp populations, which results in significant economic losses to aquaculture farmers. To prevent the antibiotics abuse, which has become a serious threat to human health, novel anti-infective strategies are urgently required to control V. parahaemolyticus. Antimicrobial peptides, which exhibit favourable germicidal activity compared to traditional antibiotics, can be used as a key method to prevent and treat bacterial diseases. Herein, an antimicrobial peptide, bomidin, was expressed through genetic engineering technology. The minimum inhibitory concentration (MIC) of bomidin showed a significant inhibitory effect on V. parahaemolyticus that was equivalent to that of ampicillin. Subsequently, the mechanism of action of recombinant bomidin was explored using PNP and ONPG assays to investigate the effects on membrane permeability. These assays indicated that bomidin penetrated the germ membrane and induced the release of cytoplasmic contents and ultimately interacted with DNA to form a bomidin-DNA complex that inhibits bacterial survival. Transmission electron microscopy and scanning electron microscopy revealed that bomidin could cause damage and dysfunction to the cell wall and membrane. Bomidin was nontoxic to mouse red blood cells within a concentration range that was much larger than the MIC. Toxicity assays revealed that 0.02 mg/mL bomidin was safe for use with juvenile freshwater prawns of M. rosenbergii and significantly inhibited the growth of V. parahaemolyticus in cultured water. These results demonstrated that synthetic peptide bomidin had great antibacterial effect against V. parahaemolyticus and therefore a therapeutic potential in aquaculture.
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http://dx.doi.org/10.1007/s12602-021-09857-6DOI Listing
October 2021

Simultaneous PET/fMRI Detects Distinctive Alterations in Functional Connectivity and Glucose Metabolism of Precuneus Subregions in Alzheimer's Disease.

Front Aging Neurosci 2021 24;13:737002. Epub 2021 Sep 24.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

As a central hub in the interconnected brain network, the precuneus has been reported showing disrupted functional connectivity and hypometabolism in Alzheimer's disease (AD). However, as a highly heterogeneous cortical structure, little is known whether individual subregion of the precuneus is uniformly or differentially involved in the progression of AD. To this end, using a hybrid PET/fMRI technique, we compared resting-state functional connectivity strength (FCS) and glucose metabolism in dorsal anterior (DA_pcu), dorsal posterior (DP_pcu) and ventral (V_pcu) subregions of the precuneus among 20 AD patients, 23 mild cognitive impairment (MCI) patients, and 27 matched cognitively normal (CN) subjects. The sub-parcellation of precuneus was performed using a K-means clustering algorithm based on its intra-regional functional connectivity. For the whole precuneus, decreased FCS ( = 0.047) and glucose hypometabolism ( = 0.006) were observed in AD patients compared to CN subjects. For the subregions of the precuneus, decreased FCS was found in DP_pcu of AD patients compared to MCI patients ( = 0.011) and in V_pcu for both MCI ( = 0.006) and AD ( = 0.008) patients compared to CN subjects. Reduced glucose metabolism was found in DP_pcu of AD patients compared to CN subjects ( = 0.038) and in V_pcu of AD patients compared to both MCI patients ( = 0.045) and CN subjects ( < 0.001). For both FCS and glucose metabolism, DA_pcu remained relatively unaffected by AD. Moreover, only in V_pcu, disruptions in FCS ( = 0.498, = 0.042) and hypometabolism ( = 0.566, = 0.018) were significantly correlated with the cognitive decline of AD patients. Our results demonstrated a distinctively disrupted functional and metabolic pattern from ventral to dorsal precuneus affected by AD, with V_pcu and DA_pcu being the most vulnerable and conservative subregion, respectively. Findings of this study extend our knowledge on the differential roles of precuneus subregions in AD.
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http://dx.doi.org/10.3389/fnagi.2021.737002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498203PMC
September 2021

Subxiphoid thoracoscopic thymectomy for myasthenia gravis.

Interact Cardiovasc Thorac Surg 2021 Oct 9. Epub 2021 Oct 9.

Department of Cardiothoracic Surgery, Xuzhou Central Hospital, Xuzhou, China.

We investigated the efficacy of subxiphoid thoracoscopic thymectomy in patients with myasthenia gravis. The data of 37 consecutive cases were reviewed. 2 cases of postoperative myasthenia gravis crisis and 4 cases of residual mediastinal fat tissue were recorded. Moreover, 29 patients presented the neurological outcomes, and complete stable remission was achieved in 5 (17.2%) cases. Subxiphoid thymectomy is technically feasible. High-quality evidence is warranted before this approach can be recommended.
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http://dx.doi.org/10.1093/icvts/ivab262DOI Listing
October 2021

Accuracy of intraocular lens calculation formulas in patients undergoing combined phakic intraocular lens removal and cataract surgery.

Am J Ophthalmol 2021 Oct 5. Epub 2021 Oct 5.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.

Purpose: To investigate the prediction accuracy of intraocular lens (IOL) calculation formulas, and the impact of anterior chamber depth (ACD) and lens thickness (LT) measurement errors on IOL power calculation in patients undergoing combined phakic intraocular lens (PIOL) removal and cataract surgery.

Design: Retrospective, consecutive case-series study.

Methods: Thirty-six PIOL implanted eyes (12 anterior chamber PIOLs [AC-PIOL] and 24 posterior chamber PIOLs [PC-PIOL]) undergoing cataract surgery were included. The prediction accuracy of new formulas (Barrett Universal II [BUII], Emmetropia Verifying Optical [EVO], Kane, and Ladas Super formula [LSF]) and traditional formulas (Haigis, Hoffer Q, Holladay 1 and SRK/T) with or without Wang-Koch (WK) axial length (AL) adjustment was evaluated. The influence of ACD and LT measurement errors of IOLMaster 700 on refractive outcomes was also investigated.

Results: The Kane and traditional formulas with WK AL adjustment had no significant systematic prediction error (PE) and displayed smaller median absolute error, while the other formulas showed significant hyperopia shift (P < 0.05) and relatively lower prediction accuracy. The accuracy rate of IOLMaster 700 in measuring ACD and LT was 100% in eyes with AC-PIOL implantation, and 37.50% in the PC-PIOL subgroup. No significant difference was observed in refractive outcomes of formulas using correct and wrong parameters in the PC-PIOL subgroup (P > 0.05).

Conclusions: The Kane and traditional formulas with WK AL adjustment exhibited relatively higher prediction accuracy in patients who underwent combined PIOL removal and cataract surgery. The IOLMaster 700 displayed low accuracy in ACD and LT measurements for PC-PIOL implanted eyes, but showed negligible impact on IOL prediction accuracy.
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http://dx.doi.org/10.1016/j.ajo.2021.09.035DOI Listing
October 2021

Imaging characteristics of pathologically proven adrenal adenomas with myelolipomatous degeneration: correlation with clinical and pathologic features.

Br J Radiol 2021 Oct 18:20210555. Epub 2021 Oct 18.

Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Objectives: Adrenal adenoma with myelolipomatous degeneration (AMD) is a rarely reported and often overlooked entity. The aim of this study is to improve understanding of these lesions by characterizing the imaging findings with pathologic and clinical correlation.

Methods: In the largest series to date, we report 11 nodules in 11 patients confirmed with a pathologic diagnosis of AMD. The available cross-sectional imaging and histopathologic features were reviewed by two radiologists and two pathologists, respectively. Clinical and laboratory data for each patient were obtained from the electronic medical records, when available.

Results: All 11 patients had a CT prior to resection or biopsy of the adrenal nodule, with five having received an adrenal mass protocol study. An MRI was available in three patients. The median size of the nodules on imaging was 4.5 cm (range 2.8-8.7) and all but one had macroscopic fat. The largest focus of macroscopic fat had a median size of 0.7 cm (range 0.2-1.6) and on average was 14.4% the size of the tumor, using greatest dimensions. Four (36.4%) patients had a diagnosis of Cushing syndrome prior to nodule resection.

Conclusions: Not all adrenal nodules with macroscopic fat on imaging are pure myelolipomas. An AMD should be considered, especially if the foci of fat are small and other features of an adenoma are present. Some may also be associated with Cushing syndrome.

Advances In Knowledge: Myelolipomatous degeneration within an adrenal adenoma has only rarely been previously reported with very few reports emphasizing the imaging features. There may be an association with cortisol hypersecretion and improved recognition of this entity could lead to changes in clinical management.
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http://dx.doi.org/10.1259/bjr.20210555DOI Listing
October 2021

Voltage cycling process for the electroconversion of biomass-derived polyols.

Proc Natl Acad Sci U S A 2021 Oct;118(41)

Department of Chemical Engineering, Stanford University, Stanford, CA 94305;

Electrification of chemical reactions is crucial to fundamentally transform our society that is still heavily dependent on fossil resources and unsustainable practices. In addition, electrochemistry-based approaches offer a unique way of catalyzing reactions by the fast and continuous alteration of applied potentials, unlike traditional thermal processes. Here, we show how the continuous cyclic application of electrode potential allows Pt nanoparticles to electrooxidize biomass-derived polyols with turnover frequency improved by orders of magnitude compared with the usual rates at fixed potential conditions. Moreover, secondary alcohol oxidation is enhanced, with a ketoses-to-aldoses ratio increased up to sixfold. The idea has been translated into the construction of a symmetric single-compartment system in a two-electrode configuration. Its operation via voltage cycling demonstrates high-rate sorbitol electrolysis with the formation of H as a desired coproduct at operating voltages below 1.4 V. The devised method presents a potential approach to using renewable electricity to drive chemical processes.
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http://dx.doi.org/10.1073/pnas.2113382118DOI Listing
October 2021

Differential lipids in pregnant women with subclinical hypothyroidism and their correlation to the pregnancy outcomes.

Sci Rep 2021 Oct 4;11(1):19689. Epub 2021 Oct 4.

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Subclinical hypothyroidism (SCH) has become a prevalent complication in pregnancy. Recent research links SCH to disturbed thyroid lipid profile; however, it is unclear how lipid metabolism disorders contribute to the pathogenesis of SCH during pregnancy. Thus, we used nontargeted lipidomics to identify and compare the lipids and metabolites expressed by pregnant women with SCH and healthy pregnant women. Multivariate analysis revealed 143 lipid molecules differentially expressed between the SCH group and the control group. Based on fold change, 30 differentially expressed lipid metabolites are potential biomarkers. KEGG pathway enrichment analysis showed that the differentially expressed metabolites participate in several pathways, including response to pathogenic Escherichia coli infection, regulation of lipolysis in adipocytes, metabolic pathways, glycerophospholipid metabolism, and fat digestion and absorption pathways. Correlation analyses revealed sphingomyelin (SM) and phosphatidylcholine (PC) positively correlate to tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6), while phosphatidylglycerol (PG), and phosphatidylinositol (PI) negatively correlate with them. In addition, PG positively correlates to birth weight. Thus, the lipid profile of pregnant women with SCH is significantly different from that of healthy pregnant women. Lipid molecules associated with the differential lipid metabolism, such as SM, phosphatidylethanolamine (PE), and PI, should be further investigated for their roles in the pathogenesis of SCH in pregnancy, as they might be targets for reducing the incidence of adverse pregnancy outcomes.
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http://dx.doi.org/10.1038/s41598-021-99252-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490420PMC
October 2021

Anomalous interfacial dynamics of single proton charges in binary aqueous solutions.

Sci Adv 2021 Oct 29;7(40):eabg8568. Epub 2021 Sep 29.

Laboratory of Nanoscale Biology, Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abg8568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480921PMC
October 2021

Inhibition of nitrite-oxidizing bacteria in automatic recycling PN/ANAMMOX under mainstream conditions.

Bioresour Technol 2021 Sep 13;342:125935. Epub 2021 Sep 13.

College of Environmental Science and Engineering, Yangzhou University, Yangzhou 225127, China.

At present, sustainable and stable partial nitrification has not been widely achieved in the mainstream PN/ANAMMOX process. Here, the feasibility of sustainable and stable partial nitrification was demonstrated in automatic recycling PN/ANAMMOX reactor under mainstream conditions using both simulation and experimental methods. Stable nitrite accumulation in the aerobic zone could be achieved via regulating dissolved oxygen (DO) concentrations and sludge retention time (SRT). The DO concentrations required for the repression of nitrite-oxidizing bacteria (NOB) were lower at longer SRTs. The DO concentrations and SRTs required for NOB repression were lower at lower temperatures. However, NOB repression was diminished by a persistent low DO and short SRT under mainstream conditions. With the introduction of automatic recycling, sustainable and stable partial nitrification was achieved. Effluent recycling could limit the nitrite-nitrogen required for NOB growth. Collectively, effluent recycling may serve as a feasible and useful strategy for NOB inhibition during the PN/ANAMMOX process.
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http://dx.doi.org/10.1016/j.biortech.2021.125935DOI Listing
September 2021

Vein-first versus artery-first ligation procedure for lung cancer surgery: An updated review.

J Cardiothorac Surg 2021 Sep 26;16(1):272. Epub 2021 Sep 26.

Department of Thoracic Surgery, Xuzhou Central Hospital, 199 Jiefang South Road, Xuzhou, 221009, China.

Background: The optimal sequence of pulmonary vessel interruption during lung cancer resection remains controversial. This review aimed to elucidate the association of vein-first versus artery-first ligation and survival of the patients.

Methods: We searched PubMed, Web of Science, Scopus, Embase, Cochrane Library and Google Scholar from their inception to September 2021 for published articles that compared vein-first (the pulmonary vein was interrupted first) and artery-first procedure (the pulmonary artery was ligated first) during lung cancer surgery.

Results: Finally, a total of 13 full articles were obtained. First, 7 studies with survival information were included for meta-analyses. As compared with the artery-first ligation, vein-first approach did not decrease the risk of local recurrence (risk ratio [RR] 0.92 in favour of vein-first; 95% confidence interval [CI] 0.61-1.39, p = 0.68) or distant metastasis (RR 0.92; 95% CI 0.30-2.85, p = 0.89); but it was associated with better disease-free survival (RR 0.52; 95% CI 0.37-0.73, p < 0.01) as well as 5-year overall survival (RR 0.60; 95% CI 0.41-0.86, p < 0.01). In addition, the operative time, intraoperative blood loss, total complications, and length of postoperative stay were mainly comparable between the two groups. Second, 7 studies provided the data of tumor cells indicated by different biomarkers and detection methods; and 3 of these reports showed that vein-first ligation decreased the extent of intraoperative tumor dissemination. However, a quantitative meta-analysis was not possible due to the significant heterogeneity.

Conclusion: Vein-first ligation in lung cancer surgery may be associated with improved survival of the patients, which might be ascribed to potentially lower risk of tumor cell dissemination. Well-designed, large-scale trials are warranted to clarify these occasional findings.
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http://dx.doi.org/10.1186/s13019-021-01658-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474918PMC
September 2021

Monocyte Gene Expression Distinguishes Enhancing Brain Parenchymal Cysticercal Granulomas From Tuberculomas.

Open Forum Infect Dis 2021 Sep 12;8(9):ofab427. Epub 2021 Aug 12.

Department of Neurological Sciences, Christian Medical College, Vellore, Tamilnadu, India.

Background: In patients with enhancing brain parenchymal lesions, parenchymal neurocysticercosis (pNCC) is often difficult to distinguish from tuberculoma, necessitating biopsy or empirical therapy.

Methods: In a prospective study, peripheral blood monocytes were isolated from patients with definitive pNCC (n = 39) and brain tuberculomas (n = 20). Patients with tuberculomas were diagnosed by the presence of concurrent systemic tuberculosis (n = 7), pathological or bacteriological confirmation (n = 5), and resolution of typical brain lesions following a therapeutic trial of antituberculous therapy (n = 8). Expressions of 14 NCC-associated monocyte genes were determined by quantitative polymerase chain reaction and analyzed for diagnostic usefulness between the 2 groups.

Results: Expression of 7 genes (TAX1BP1, RAP1A, PLCG2, TOR3A, GBP1P1, LRRFIP2, and FEZ2) was significantly higher in pNCC patients than in tuberculoma patients, with TAX1BP1 and RAP1A expressions more than 22- and 5-fold higher in pNCC patients. TAX1BP1 had the highest sensitivity of 66.7% at a specificity of 100% in discriminating pNCC from tuberculoma. A combination of TAX1BP1 and RAP1A increased the sensitivity to 84.6%, and including GBP1P1 with TAX1BP1 and RAP1A further increased sensitivity to 87.2% while maintaining specificity of 100%.

Conclusions: Expression of a panel of genes in blood monocytes distinguishes pNCC from brain tuberculomas in patients with enhancing brain lesions.
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http://dx.doi.org/10.1093/ofid/ofab427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454506PMC
September 2021

Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation.

Cell Rep 2021 Sep;36(12):109740

Department of Pharmacology, Zhejiang University City College, Hangzhou 310015, China. Electronic address:

Bub1 is required for the kinetochore/centromere localization of two essential mitotic kinases Plk1 and Aurora B. Surprisingly, stable depletion of Bub1 by ∼95% in human cells marginally affects whole chromosome segregation fidelity. We show that CENP-U, which is recruited to kinetochores by the CENP-P and CENP-Q subunits of the CENP-O complex, is required to prevent chromosome mis-segregation in Bub1-depleted cells. Mechanistically, Bub1 and CENP-U redundantly recruit Plk1 to kinetochores to stabilize kinetochore-microtubule attachments, thereby ensuring accurate chromosome segregation. Furthermore, unlike its budding yeast homolog, the CENP-O complex does not regulate centromeric localization of Aurora B. Consistently, depletion of Bub1 or CENP-U sensitizes cells to the inhibition of Plk1 but not Aurora B kinase activity. Taken together, our findings provide mechanistic insight into the regulation of kinetochore function, which may have implications for targeted treatment of cancer cells with mutations perturbing kinetochore recruitment of Plk1 by Bub1 or the CENP-O complex.
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http://dx.doi.org/10.1016/j.celrep.2021.109740DOI Listing
September 2021

Amyloid-Beta Influences Memory Functional Connectivity During Memory Retrieval in Alzheimer's Disease.

Front Aging Neurosci 2021 1;13:721171. Epub 2021 Sep 1.

Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Amnesia in Alzheimer's disease (AD) appears early and could be caused by encoding deficiency, consolidation dysfunction, and/or impairment in the retrieval of stored memory information. The relationship between AD pathology biomarker β-amyloid and memory dysfunction is unclear. The memory task functional MRI and amyloid PET were simultaneously performed to investigate the relationship between memory performance, memory phase-related functional connectivity, and cortical β-amyloid deposition. We clustered functional networks during memory maintenance and compared network connectivity between groups in each memory phase. Mediation analysis was performed to investigate the mediator between β-amyloid and related cognitive performance. Alzheimer's disease was primarily characterized by decreased functional connectivity in a data-driven network composed of an default mode network, limbic network, and frontoparietal network during the memory maintenance (0.205 vs. 0.236, = 0.04) and retrieval phase (0.159 vs. 0.183, = 0.017). Within the network, AD had more regions with reduced connectivity during the retrieval than the maintenance and encoding phases (chi-square = 0.01 and < 0.001). Furthermore, the global cortical β-amyloid negatively correlated with network connectivity during the memory retrieval phase ( = - 0.247, = 0.032), with this relationship mediating the effect of cortical β-amyloid on memory performance (average causal mediation effect = - 0.05, = 0.035). We demonstrated that AD had decreased connectivity in specific networks during the memory retrieval phase. Impaired functional connectivity during memory retrieval mediated the adverse effect of β-amyloid on memory. These findings help to elucidate the involvement of cortical β-amyloid (Aβ) in the memory performance in the early stages of AD.
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http://dx.doi.org/10.3389/fnagi.2021.721171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444623PMC
September 2021

DNA Methyltransferases Contribute to Cold Tolerance in Ticks and (Acari: Ixodidae).

Front Vet Sci 2021 26;8:726731. Epub 2021 Aug 26.

Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, College of Life Sciences, Hebei Normal University, Shijiazhuang, China.

DNA methylation, mediated by DNA methyltransferases (Dnmts), is a typical epigenetic process that plays an important role in affecting organism acclimatization and adaptation to environmental changes. However, information about Dnmts and their associations with the cold tolerance of ticks remains meager. Hence, in the present study, the Dnmts in important vector ticks and were cloned and identified, and their functions in cold response were further explored. Results showed that the length of and in , and and in were 1,284, 549, 1,500, and 1,613 bp, respectively. Bioinformatics in protein analysis revealed that they were all unstable hydrophilic proteins and were mainly characterized with Dcm (DNA cytosine methyltransferase domain), Dnmt1-RFD (DNA methyltransferase replication foci domain), zf-CXXC (zinc finger-CXXC domain), and BAH (Bromo adjacent homology domain). The relative expression of these was reduced after cold treatment for 3 days ( < 0.05), and increased with the extension of treatment. Western blot revealed that Dnmt1 decreased first and then increased significantly ( < 0.05) in both tick species, whereas other Dnmts fluctuated at varying degrees. RNA interference significantly silenced the genes ( < 0.01), and mortality increased significantly ( < 0.05), when exposed to sub-lethal temperature, underscoring the important roles of Dnmts during the cold response of and . The above results lay the foundation for further understanding of the epigenetic regulation of DNA methylation in cold acclimatization and adaptation of ticks.
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http://dx.doi.org/10.3389/fvets.2021.726731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426640PMC
August 2021

2,5-dimethyl celecoxib induces apoptosis and autophagy via activation of ROS/JNK axis in nasopharyngeal carcinoma cells.

Aging (Albany NY) 2021 09 12;13(17):21483-21496. Epub 2021 Sep 12.

Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Shanxi 710061, China.

2,5-dimethyl celecoxib (DMC), a close derivative of celecoxib, has also been reported to have anticancer effects. However, the effects and underlying molecular mechanisms of DMC with respect to nasopharyngeal carcinoma are still largely unknown. In this study, we present that DMC has displayed anticancer potency in nasopharyngeal carcinoma and . Mechanistically, we found DMC induced apoptosis and autophagy for anticancer therapy against nasopharyngeal carcinoma. Furthermore, DMC-induced autophagy could remarkably attenuate after the treatment of reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC) and c-Jun N-terminal kinase (JNK) inhibitor SP600125 (SP). Taken together, these results suggested DMC induced apoptosis and autophagic death via activation of ROS/JNK axis in NPC cells, which providing us new insights into developing potential therapeutic agents for nasopharyngeal carcinoma patients.
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http://dx.doi.org/10.18632/aging.203488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457580PMC
September 2021

A multi-scale gated multi-head attention depthwise separable CNN model for recognizing COVID-19.

Sci Rep 2021 09 10;11(1):18048. Epub 2021 Sep 10.

Department of Electrical Information and Automation, Tianjin University of Science and Technology, Tianjin, 300222, China.

Coronavirus 2019 (COVID-19) is a new acute respiratory disease that has spread rapidly throughout the world. In this paper, a lightweight convolutional neural network (CNN) model named multi-scale gated multi-head attention depthwise separable CNN (MGMADS-CNN) is proposed, which is based on attention mechanism and depthwise separable convolution. A multi-scale gated multi-head attention mechanism is designed to extract effective feature information from the COVID-19 X-ray and CT images for classification. Moreover, the depthwise separable convolution layers are adopted as MGMADS-CNN's backbone to reduce the model size and parameters. The LeNet-5, AlexNet, GoogLeNet, ResNet, VGGNet-16, and three MGMADS-CNN models are trained, validated and tested with tenfold cross-validation on X-ray and CT images. The results show that MGMADS-CNN with three attention layers (MGMADS-3) has achieved accuracy of 96.75% on X-ray images and 98.25% on CT images. The specificity and sensitivity are 98.06% and 96.6% on X-ray images, and 98.17% and 98.05% on CT images. The size of MGMADS-3 model is only 43.6 M bytes. In addition, the detection speed of MGMADS-3 on X-ray images and CT images are 6.09 ms and 4.23 ms for per image, respectively. It is proved that the MGMADS-3 can detect and classify COVID-19 faster with higher accuracy and efficiency.
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http://dx.doi.org/10.1038/s41598-021-97428-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433233PMC
September 2021

Antiviral and virucidal activities of lycorine on duck tembusu virus in vitro by blocking viral internalization and entry.

Poult Sci 2021 Oct 25;100(10):101404. Epub 2021 Jul 25.

College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Hefei 230036, China. Electronic address:

Duck tembusu virus (DTMUV) was firstly identified in 2010 in China; since then, it has caused enormous economic loss to breeding industry. Great efforts have been made to develop drugs and vaccines against DTMUV. However, current available vaccines or anti-DTMUV drugs are consistently inefficient. Hence, various more broadly effective drugs have become important for the treatment of DTMUV infection; among these, lycorine, one of the important sources of active alkaloids, is a promising example. Nevertheless, it is not known whether lycorine has any antiviral activities against DTMUV. Therefore, the purpose of the present study is to investigate the anti-DTMUV abilities of lycorine. The cytotoxicity of lycorine was evaluated on BHK-21 cells by CCK-8 assay, and its antiviral effect against DTMUV was examined by real-time PCR assays, virus titer determination, Western blot and immunofluorescence (IFA) assays, respectively. Furthermore, the underlying mechanisms of the anti-DTMUV effects of lycorine were also investigated. The results indicated that the highest nontoxicity concentration of lycorine on BHK-21 cells was 5 µM. Lycorine possessed the antiviral ability against DTMUV on BHK-21 cells, as demonstrated by the reduction of virus titers and copy numbers in vitro. Western blot and IFA analysis showed the inhibitory effect of lycorine on DTMUV envelope (E) protein expression. Moreover, using time-of-addition assays, we found that lycorine displays its antivirus and virucidal activities through blocking viral internalization and entry in vitro. Taken together, our findings firstly demonstrate the antiviral activities of lycorine against DTMUV, suggesting that lycorine can be a potential drug for the treatment of DTMUV infection.
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http://dx.doi.org/10.1016/j.psj.2021.101404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414183PMC
October 2021

Surgical perspective in neoadjuvant chemoimmunotherapy for stage II-III non-small cell lung cancer.

Thorac Cancer 2021 Oct 30;12(20):2796-2802. Epub 2021 Aug 30.

Department of Thoracic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Background: There are many studies on neoadjuvant immunotherapy for locally advanced non-small cell lung cancer (NSCLC) patients. Expert consensus recommends neoadjuvant immunotherapy for patients with resectable stage IB-IIIA NSCLC. However, there are few clinical studies or cases to verify this.

Methods: Data were collected from all NSCLC patients who underwent surgical resection after neoadjuvant chemoimmunotherapy admitted to the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital between September 2020 and April 2021. Data collected included patient information, relevant examination results, intraoperative parameters, postoperative complications, pathological changes, and 90-day mortality.

Results: In total, 25 patients achieved R0 resection. Eleven (44%) patients completed surgery by thoracotomy, and three (12%) procedures were changed from minimally invasive procedures due to dense adhesions of hilar lymph nodes, which rendered it difficult to dissect the blood vessels. Thirteen (52%) patients achieved a major pathological response (MPR) with eight (32%) of these patients having a pathological complete response (pCR). Twenty-two (88%) patients showed radiological regression, and three (12%) patients had stable disease. The median drainage time was 8.50 (3-27) days. Thirteen (52%) postoperative complications were observed, but none were above grade 3.

Conclusions: In this study, neoadjuvant chemoimmunotherapy was found to reduce tumor volume, cause pathological downstaging, and raise the surgical resection rate of patients with locally advanced NSCLC, and achieve a 100% R0 resection rate. There was an acceptable rate of postoperative complications. Thus, neoadjuvant chemoimmunotherapy is safe and practical.
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http://dx.doi.org/10.1111/1759-7714.14127DOI Listing
October 2021

Subtype-selective positive modulation of K 2 channels depends on the HA/HB helices.

Br J Pharmacol 2021 Aug 30. Epub 2021 Aug 30.

Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, California, USA.

Background And Purpose: In the activated state of small-conductance Ca -activated potassium (K 2) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates K 2.2a and K 2.3 channel activity but not the K 2.1 and K 3.1 subtypes.

Experimental Approach: Site-directed mutagenesis, patch-clamp recordings and in silico modelling were utilised to explore the structural determinants for the subtype-selective modulation of K 2 channels by CyPPA.

Key Results: Mutating residues in the HA (V420) and HB (K467) helices of K 2.2a channels to their equivalent residues in K 3.1 channels diminished the potency of CyPPA. CyPPA elicited prominent responses on mutant K 3.1 channels with an arginine residue in the HB helix substituted for its equivalent lysine residue in the K 2.2a channels (R355K). K 2.1 channels harbouring a three-amino-acid insertion upstream of the cognate R438 residues in the HB helix showed no response to CyPPA, whereas the deletion mutant (K 2.1_ΔA434/Q435/K436) became sensitive to CyPPA. In molecular dynamics simulations, CyPPA docked between calmodulin C-lobe and the HA/HB helices widens the cytoplasmic gate of K 2.2a channels.

Conclusion And Implications: Selectivity of CyPPA among K 2 and K 3.1 channel subtypes relies on the HA/HB helices.
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http://dx.doi.org/10.1111/bph.15676DOI Listing
August 2021

Prognostic significance of the aberrant expression of neuroendocrine markers in melanomas.

Diagn Pathol 2021 Aug 28;16(1):78. Epub 2021 Aug 28.

Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China.

Background: Melanoma is a highly malignant tumor with diverse histopathological morphology and frequent aberrant expression of immunohistochemical markers. An occasionally reported phenomenon is the abnormal expression of neuroendocrine markers. Awareness of this situation is essential because such tumors need to be differentiated from neuroendocrine tumors because of their significant therapeutic and prognostic implications.

Methods: We retrospectively analyzed the expression of chromogranin A (CgA), synaptophysin (Syn) and CD56 as neuroendocrine markers in 308 cases with melanomas. Kaplan-Meier curves and Cox regression analyses were used for overall survival (OS) and progression-free survival (PFS) evaluation and comparison between neuroendocrine markers expression status in all melanoma cases or stage I-II cases.

Results: The expression of neuroendocrine markers in melanomas is not uncommon. CgA was positive in 6/304 (2.0%) cases, Syn in 26/304 (8.6%), and CD56 in 56/189 (29.6%). None of the cases co-expressed all the three markers. Focal or weak expression of at least one neuroendocrine marker was identified in 70/188 (37.2%) cases. The expression of CgA was correlated with age (p = 0.019), while the positive expression of Syn and CD56 showed borderline significance (p = 0.078 and 0.083, respectively), but not for any neuroendocrine marker expression. The expression of any neuroendocrine marker showed borderline significance with staging (p = 0.066). The expression of CgA, Syn, CD56, or any neuroendocrine marker did not correlate with clinicopathological features including sex, specimen type, origin, location, and histology subtype. Survival analyses revealed that the expression of neuroendocrine markers was not associated with OS or PFS.

Conclusions: Our study confirms that neuroendocrine marker expression is a common phenomenon in melanomas, but it has no prognostic significance. Nevertheless, awareness can avoid misdiagnosis in cases of melanomas with unusual morphology and immunophenotypes.
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http://dx.doi.org/10.1186/s13000-021-01135-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403415PMC
August 2021

Removal of recalcitrant organics in reverse osmosis concentrate from coal chemical industry by UV/HO and UV/PDS: Efficiency and kinetic modeling.

Chemosphere 2021 Aug 23;287(Pt 1):131999. Epub 2021 Aug 23.

Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

The lack of stability in catalytic ozonation treatment of reverse osmosis (RO) concentrate from coal chemical industry calls for new advanced oxidation processes. Herein, UV/HO and UV/PDS were employed to remove the bulk recalcitrant organics in the RO concentrate with a focus on the process efficiency and kinetic modeling. Results show that UV/HO overmatched UV/PDS in reducing the COD and DOC of the wastewater and the advantage became more evident in aspects of biodegradability improvement and energy cost. Specifically, the COD and DOC were removed by 62.0% and 55.5% with UV/HO (6 mM) while the BOD/COD was elevated to 0.54 at a specific energy consumption of 0.83 kWh g (lab-scale). The UV/HO process also exhibited a good adaptability to the fluctuation of wastewater quality. Afterwards, the reaction rate constants of the bulk organics upon UV photolysis and HO oxidation were calculated based on pseudo-first-order kinetics and radical steady-state approximation of DOC removal in the bench-scale UV/HO reactor. A computational fluid dynamics model was then developed for the analysis of distributions of flow, radiation and chemicals in flow-through reactors which facilitated the practical process efficiency assessment. This work demonstrates the applicability of UV/HO in removing recalcitrant organics in the RO concentrate and presents an approach from bench-scale experiments to flow-through system evaluation.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131999DOI Listing
August 2021

Joint Lossless Image Compression and Encryption Scheme Based on CALIC and Hyperchaotic System.

Entropy (Basel) 2021 Aug 23;23(8). Epub 2021 Aug 23.

School of Computer Science and Technology, Harbin Institute of Technology, Weihai 264209, China.

For efficiency and security of image transmission and storage, the joint image compression and encryption method that performs compression and encryption in a single step is a promising solution due to better security. Moreover, on some important occasions, it is necessary to save images in high quality by lossless compression. Thus, a joint lossless image compression and encryption scheme based on a context-based adaptive lossless image codec (CALIC) and hyperchaotic system is proposed to achieve lossless image encryption and compression simultaneously. Making use of the characteristics of CALIC, four encryption locations are designed to realize joint image compression and encryption: encryption for the predicted values of pixels based on gradient-adjusted prediction (GAP), encryption for the final prediction error, encryption for two lines of pixel values needed by prediction mode and encryption for the entropy coding file. Moreover, a new four-dimensional hyperchaotic system and plaintext-related encryption based on table lookup are all used to enhance the security. The security tests show information entropy, correlation and key sensitivity of the proposed methods reach 7.997, 0.01 and 0.4998, respectively. This indicates that the proposed methods have good security. Meanwhile, compared to original CALIC without security, the proposed methods increase the security and reduce the compression ratio by only 6.3%. The test results indicate that the proposed methods have high security and good lossless compression performance.
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http://dx.doi.org/10.3390/e23081096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394254PMC
August 2021

Stem Cell Theory of Cancer: Origin of Tumor Heterogeneity and Plasticity.

Cancers (Basel) 2021 Aug 9;13(16). Epub 2021 Aug 9.

Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

In many respects, heterogeneity is one of the most striking revelations and common manifestations of a stem cell origin of cancer. We observe heterogeneity in myriad mixed tumors including testicular, lung, and breast cancers. We recognize heterogeneity in diverse tumor subtypes in prostate and kidney cancers. From this perspective, we illustrate that one of the main stem-ness characteristics, i.e., the ability to differentiate into diverse and multiple lineages, is central to tumor heterogeneity. We postulate that cancer subtypes can be meaningless and useless without a proper theory about cancer's stem cell versus genetic origin and nature. We propose a unified theory of cancer in which the same genetic abnormalities, epigenetic defects, and microenvironmental aberrations cause different effects and lead to different outcomes in a progenitor stem cell versus a mature progeny cell. We need to recognize that an all-encompassing genetic theory of cancer may be incomplete and obsolete. A stem cell theory of cancer provides greater universality, interconnectivity, and utility. Although genetic defects are pivotal, cellular context is paramount. When it concerns tumor heterogeneity, perhaps we need to revisit the conventional wisdom of precision medicine and revise our current practice of targeted therapy in cancer care.
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http://dx.doi.org/10.3390/cancers13164006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394880PMC
August 2021

Accessibility of Medicines for Children: A Systematic Review.

Front Pharmacol 2021 5;12:691606. Epub 2021 Aug 5.

Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China.

Accessibility of medicines for children is a matter of global concern. Medicines prescribed for children are often off-label. To formulate appropriate policies and undertake necessary interventions to improve access to medicines for children, it is necessary to evaluate the accessibility of medicines for children. However, there is no systematic review of the medicine accessibility for children. Relevant studies were identified through searching Pubmed, Embase, CNKI, Wanfang, VIP, World Health Organization website, and Health Action International website. Besides, the references of included studies as a supplementary search were read. We extracted the basic information of articles (the first author, published year, the name of journal, research institution, etc.), the basic study characteristics (survey area, survey time, survey method, survey medicine lists, the number of medicine outlets surveyed, etc.), and the study results (the current situation of the accessibility of medicines for children, including the availability, price, and affordability of medicines for children, etc.). Two reviewers independently selected studies and extracted the data. Descriptive analysis methods to analyze the current situation of the accessibility of children's medicines were used. A total of 18 multicenter cross-sectional studies were included in this systematic review, which were from low-income and middle-income countries. Seventeen studies (17/18, 94.4%) used the WHO/Health Action International (HAI) medicine price methodology to investigate the accessibility of medicines for children. Fifteen studies (15/18, 83.3%) were selected to investigate medicines based on the WHO Model List of Essential Medicines for Children (WHO EMLc). In the public sectors, the availability of originator brands (OBs) ranged from 0 to 52.0%, with a median of 24.2%, and the availability of lowest-priced generics (LPGs) ranged from 17.0 to 72.6%, with a median of 38.1%. In the private sectors, the availability of OBs ranged from 8.9 to 80%, with a median of 21.2%. The availability of LPGs ranged from 20.6 to 72.2%, with a median of 35.9%. In most regions, the availability of OBs in the private sectors was higher than in the public sectors. Collectively, in the price of medicines for children, the median price ratio (MPR) of the OBs in the public sectors and private sectors were much higher than that of the LPGs. And the affordability of the LPGs in the public sectors and private sectors was higher than that of originator brands (OBs). The availability of medicines for children is low in both the public sectors and private sectors in low-income and middle-income countries. The MPR of originator brands (OBs) is higher than that of lowest-priced generics (LPGs), and the most lowest-priced generics (LPGs) have better affordability.
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http://dx.doi.org/10.3389/fphar.2021.691606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375435PMC
August 2021
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