Publications by authors named "Cheng Cheng"

785 Publications

A general end-to-end diagnosis framework for manufacturing systems.

Natl Sci Rev 2020 Feb 21;7(2):418-429. Epub 2019 Nov 21.

State Key Laboratory of Digital Manufacturing Equipment and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

The manufacturing sector is envisioned to be heavily influenced by artificial-intelligence-based technologies with the extraordinary increases in computational power and data volumes. A central challenge in the manufacturing sector lies in the requirement of a general framework to ensure satisfied diagnosis and monitoring performances in different manufacturing applications. Here, we propose a general data-driven, end-to-end framework for the monitoring of manufacturing systems. This framework, derived from deep-learning techniques, evaluates fused sensory measurements to detect and even predict faults and wearing conditions. This work exploits the predictive power of deep learning to automatically extract hidden degradation features from noisy, time-course data. We have experimented the proposed framework on 10 representative data sets drawn from a wide variety of manufacturing applications. Results reveal that the framework performs well in examined benchmark applications and can be applied in diverse contexts, indicating its potential use as a critical cornerstone in smart manufacturing.
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http://dx.doi.org/10.1093/nsr/nwz190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289032PMC
February 2020

Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy.

Natl Sci Rev 2019 May 22;6(3):469-479. Epub 2019 Jan 22.

CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.

Standard chemotherapy regimens for remission induction of pediatric acute myeloid leukemia (AML) are associated with significant morbidity and mortality. We performed a cohort study to determine the impact of reducing the intensity of remission induction chemotherapy on the outcomes of selected children with AML treated with a low-dose induction regimen plus granulocyte colony stimulating factor (G-CSF) (low-dose chemotherapy (LDC)/G-CSF). Complete response (CR) after two induction courses was attained in 87.0% (40/46) of patients receiving LDC/G-CSF. Post-remission therapy was offered to all patients, and included standard consolidation and/or stem cell transplantation. During the study period, an additional 94 consecutive children with AML treated with standard chemotherapy (SDC) for induction (80/94 (85.1%) of the patients attained CR after induction II, = 0.953) and post-remission. In this non-randomized study, there were no significant differences in 4-year event-free (67.4 vs. 70.7%; = 0.99) and overall (70.3 vs. 74.6%, = 0.69) survival in the LDC/G-CSF and SDC cohorts, respectively. After the first course of induction, recovery of white blood cell (WBC) and platelet counts were significantly faster in patients receiving LDC/G-CSF than in those receiving SDC (11.5 vs. 18.5 d for WBCs ( < 0.001); 15.5 vs. 22.0 d for platelets ( < 0.001)). To examine the quality of molecular response, targeted deep sequencing was performed. Of 137 mutations detected at diagnosis in 20 children who attained hematological CR after two courses of LDC/G-CSF ( = 9) or SDC ( = 11), all of the mutations were below the reference value (variant allelic frequency <2.5%) after two courses, irrespective of the treatment group. In conclusion, children with AML receiving LDC/G-CSF appear to have similar outcomes and mutation clearance levels, but significantly lower toxicity than those receiving SDC. Thus, LDC/G-CSF should be further evaluated as an effective alternative to remission induction in pediatric AML.
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http://dx.doi.org/10.1093/nsr/nwz006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291445PMC
May 2019

The Added Value of Combined Timed Up and Go Test, Walking Speed, and Grip Strength on Predicting Recurrent Falls in Chinese Community-dwelling Elderly.

Clin Interv Aging 2021 5;16:1801-1812. Epub 2021 Oct 5.

Department of Rehabilitation, School of Medical Technology, Tianjin Medical University, Tianjin, People's Republic of China.

Purpose: To determine whether combined performance-based models could exert better predictive values toward discriminating community-dwelling elderly with high risk of any-falls or recurrent-falls.

Participants And Methods: This prospective cohort study included a total of 875 elderly participants (mean age: 67.10±5.94 years) with 513 females and 362 males, recruited from Hangu suburb area of Tianjin, China. All participants completed comprehensive assessments.

Methods: We documented information about sociodemographic information, behavioral characteristics and medical conditions. Three functional tests-timed up and go test (TUGT), walking speed (WS), and grip strength (GS) were used to create combined models. New onsets of any-falls and recurrent-falls were ascertained at one-year follow-up appointment.

Results: In total 200 individuals experienced falls over a one-year period, in which 66 individuals belonged to the recurrent-falls group (33%). According to the receiver operating characteristic curve (ROC), the cutoff points of TUGT, WS, and GS toward recurrent-falls were 10.31 s, 0.9467 m/s and 0.3742 kg/kg respectively. We evaluated good performance as "+" while poor performance as "-". After multivariate adjustment, we found "TUGT >10.31 s" showed a strong correlation with both any-falls (adjusted odds ratio (OR)=2.025; 95% confidence interval (CI)=1.425-2.877) and recurrent-falls (adjusted OR=2.150; 95%CI=1.169-3.954). Among combined functional models, "TUGT >10.31 s, GS <0.3742 kg/kg, WS >0.9467 m/s" showed strongest correlation with both any-falls (adjusted OR=5.499; 95%CI=2.982-10.140) and recurrent-falls (adjusted OR=8.260; 95%CI=3.880-17.585). And this combined functional model significantly increased discriminating abilities on screening recurrent-fallers than a single test (C-statistics=0.815, 95%CI=0.782-0.884, <0.001), while not better than a single test in predicting any-fallers (=0.083).

Conclusion: Elderly people with poor TUGT performance, weaker GS but quicker WS need to be given high priority toward fall prevention strategies for higher risks and frequencies. Meanwhile, the combined "TUGT-, GS-, WS+" model presents increased discriminating ability and could be used as a conventional tool to discriminate recurrent-fallers in clinical practice.
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http://dx.doi.org/10.2147/CIA.S325930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502011PMC
October 2021

Association Between Stent Implantation and Progression of Nontarget Lesions in a Rabbit Model of Atherosclerosis.

Circ Cardiovasc Interv 2021 Oct 22:CIRCINTERVENTIONS121010764. Epub 2021 Oct 22.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Progression of nontarget lesions (NTLs) after percutaneous coronary intervention (PCI) has been reported. However, it remains unknown whether progression of NTLs was causally related to stenting. This study was undertaken to test the hypothesis that stent implantation triggers acute phase response and systemic inflammation which may be associated with progression of NTLs.

Methods: Thirty New Zealand rabbits receiving endothelial denudation and atherogenic diet were randomly divided into stenting, sham, and control groups. Angiography and intravascular ultrasonography were performed in the stenting and sham groups, and stent implantation performed only in the stenting group. Histopathologic study was conducted and serum levels of APPs (acute phase proteins) measured in all rabbits. Proteomics analysis was performed to screen the potential proteins related to NTLs progression after stent implantation. The serum levels of APPs and inflammatory cytokines were measured in 147 patients undergoing coronary angiography or PCI.

Results: Plaque burden in the NTLs was significantly increased 12 weeks after stent implantation in the stenting group versus sham group. Serum levels of APPs and their protein expression in NTLs were significantly increased and responsible for stenting-triggered inflammation. In patients receiving PCI, serum levels of SAA-1 (serum amyloid A protein 1), CRP (C-reactive protein), TNF (tumor necrosis factor)-α, and IL (interleukin)-6 were substantially elevated up to 1 month post-PCI.

Conclusions: In a rabbit model of atherosclerosis, stent implantation triggered acute phase response and systemic inflammation, which was associated with increased plaque burden and pathological features of unstable plaque in NTLs. The potential mechanism involved vessel injury-triggered acute phase response manifested as increased serum levels of SAA-1, CRP, and LBP (lipopolysaccharide-binding protein) and their protein expression in NTLs. These findings provided a new insight into the relation between stent implantation and progression of NTLs, and further studies are warranted to clarify the detailed mechanism and clinical significance of these preliminary results.

Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900026393.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.121.010764DOI Listing
October 2021

A compact platform for the investigation of material dynamics in quasi-isentropic compression to ~ 19 GPa.

Sci Rep 2021 Oct 19;11(1):20688. Epub 2021 Oct 19.

Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang, 621900, China.

This paper reports on the development of a magnetically driven high-velocity implosion experiment conducted on the CQ-3 facility, a compact pulsed power generator with a load current of 2.1 MA. The current generates a high Lorentz force between inner and outer liners made from 2024 aluminum. Equally positioned photonic Doppler velocimetry probes record the liner velocities. In experiment CQ3-Shot137, the inner liner imploded with a radial converging velocity of 6.57 km/s while the outer liner expanded at a much lower velocity. One-dimensional magneto-hydrodynamics simulation with proper material models provided curves of velocity versus time that agree well with the experimental measurements. Simulation then shows that the inner liner underwent a shock-less compression to approximately 19 GPa and reached an off-Hugoniot high-pressure state. According to the scaling law that the maximum loading pressure is proportional to the square of the load current amplitude, the results demonstrate that such a compact capacitor bank as CQ-3 has the potential to generate pressure as high as 100 GPa within the inner liner in such an implosion experiment. It is emphasized that the technique described in this paper can be easily replicated at low cost.
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http://dx.doi.org/10.1038/s41598-021-99479-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526806PMC
October 2021

Peripheral Clock System Abnormalities in Patients With Parkinson's Disease.

Front Aging Neurosci 2021 1;13:736026. Epub 2021 Oct 1.

Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.

To evaluate the altered expression of peripheral clock genes, circulating melatonin levels, and their correlations with sleep-wake phenotypes including probable rapid eye movement sleep behavior disorder (pRBD) symptoms in a relatively large population of Parkinson's disease (PD) patients. We determined the expression profiles of five principal clock genes, , , , , and , in the peripheral blood mononuclear cells (PBMCs) of PD patients ( = 326), and healthy controls (HC, = 314) using quantitative real-time PCR. Melatonin concentration in the plasma of two groups was evaluated by enzyme-linked immunosorbent assay. Then we performed comprehensive association analyses on the PBMCs clock gene expression, plasma melatonin levels and sleep characteristics. Our data showed that the expression levels of , , , , and were significantly decreased in the PBMCs of PD as compared with that of HC ( < 0.05). PD patients had reduced plasma melatonin levels compared with HC ( < 0.0001). pRBD and excessive daytime sleepiness are common in these PD patients and are associated with the expression levels of all five clock genes ( = -0.344∼-0.789, < 0.01) and melatonin concentration ( = -0.509∼-0.753, < 0.01). Statistical analyses also revealed that a combination of five clock genes and melatonin could reach a high diagnostic performance (areas under the curves, 97%) for PD comorbid pRBD. This case-control study demonstrates that peripheral , , , , and melatonin levels are altered in PD patients and may serve as endogenous markers for sleep and wakefulness disturbances of PD.
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http://dx.doi.org/10.3389/fnagi.2021.736026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519399PMC
October 2021

Exploring the Molecular Mechanism of Astragali Radix-Curcumae Rhizoma against Gastric Intraepithelial Neoplasia by Network Pharmacology and Molecular Docking.

Evid Based Complement Alternat Med 2021 4;2021:8578615. Epub 2021 Oct 4.

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.

Background: Astragali Radix-Curcumae Rhizoma (ARCR), a classic drug pair, has been widely used for the treatment of gastric intraepithelial neoplasia (GIN) in China. However, the underlying mechanisms of this drug pair are still unknown. Thus, elucidating the molecular mechanism of ARCR for treating GIN is imperative.

Methods: The active components and targets of ARCR were determined from the TCMSP database, and the differentially expressed genes related to GIN were identified from the GSE130823 dataset. The protein-protein interaction (PPI) network and ARCR-active component-target-pathway network were constructed by STRING 11.0 and Cytoscape 3.7.2, respectively. In addition, a receiver operating characteristic curve (ROC) was conducted to verify the key targets, and enrichment analyses were performed using R software. Molecular docking was carried out to test the binding capacity between core active components and key targets.

Results: 31 active components were obtained from ARCR, among which 22 were hit by the 51 targets associated with GIN. Gene Ontology (GO) functional enrichment analysis showed that biological process (BP), molecular function (MF), and cellular component (CC) were most significantly enriched in response to a drug, catecholamine binding, and apical part of the cell, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated ARCR against GIN through regulation of neuroactive ligand-receptor interaction, nitrogen metabolism, calcium signaling pathway, chemical carcinogenesis-receptor activation, drug metabolism, gap junction, and cancers. In the PPI network, 15 potential targets were identified, of which nine key targets were proven to have higher diagnostic values in ROC. Molecular docking revealed a good binding affinity of active components (quercetin, bisdemethoxycurcumin, and kaempferol) with the corresponding targets (CYP3A4, CYP1A1, HMOX1, DRD2, DPP4, ADRA2A, ADRA2C, NR1I2, and LGALS4).

Conclusion: This study revealed the active components and molecular mechanism by which ARCR treatment is effective against GIN through regulating multipathway, such as neuroactive ligand-receptor interaction, nitrogen metabolism, and calcium signaling pathway.
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http://dx.doi.org/10.1155/2021/8578615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505068PMC
October 2021

Exogenous Nicotinamide Adenine Dinucleotide Attenuates Postresuscitation Myocardial and Neurologic Dysfunction in a Rat Model of Cardiac Arrest.

Crit Care Med 2021 Sep 22. Epub 2021 Sep 22.

Department of Emergency Medicine Center, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA. Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Department of Emergency Medicine, The Second Affiliated Hospital of Soochow University, Soochow, China. Departments of Internal Medicine and Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA. Department of Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA. Department of Surgery, Virginia Commonwealth University Health System, Richmond, VA.

Objectives: To investigate the therapeutic potential and underlying mechanisms of exogenous nicotinamide adenine dinucleotide+ on postresuscitation myocardial and neurologic dysfunction in a rat model of cardiac arrest.

Design: Thirty-eight rats were randomized into three groups: 1) Sham, 2) Control, and 3) NAD. Except for the sham group, untreated ventricular fibrillation for 6 minutes followed by cardiopulmonary resuscitation was performed in the control and NAD groups. Nicotinamide adenine dinucleotide+ (20 mg/kg) was IV administered at the onset of return of spontaneous circulation.

Setting: University-affiliated research laboratory.

Subjects: Sprague-Dawley rats.

Interventions: Nicotinamide adenine dinucleotide+.

Measurements And Main Results: Hemodynamic and myocardial function were measured at baseline and within 4 hours following return of spontaneous circulation. Survival analysis and Neurologic Deficit Score were performed up to 72 hours after return of spontaneous circulation. Adenosine triphosphate (adenosine triphosphate) level was measured in both brain and heart tissue. Mitochondrial respiratory chain function, acetylation level, and expression of Sirtuin3 and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9 (NDUFA9) in isolated mitochondrial protein from both brain and heart tissue were evaluated at 4 hours following return of spontaneous circulation. The results demonstrated that nicotinamide adenine dinucleotide+ treatment improved mean arterial pressure (at 1 hr following return of spontaneous circulation, 94.69 ± 4.25 mm Hg vs 89.57 ± 7.71 mm Hg; p < 0.05), ejection fraction (at 1 hr following return of spontaneous circulation, 62.67% ± 6.71% vs 52.96% ± 9.37%; p < 0.05), Neurologic Deficit Score (at 24 hr following return of spontaneous circulation, 449.50 ± 82.58 vs 339.50 ± 90.66; p < 0.05), and survival rate compared with that of the control group. The adenosine triphosphate level and complex I respiratory were significantly restored in the NAD group compared with those of the control group. In addition, nicotinamide adenine dinucleotide+ treatment activated the Sirtuin3 pathway, down-regulating acetylated-NDUFA9 in the isolated mitochondria protein.

Conclusions: Exogenous nicotinamide adenine dinucleotide+ treatment attenuated postresuscitation myocardial and neurologic dysfunction. The responsible mechanisms may involve the preservation of mitochondrial complex I respiratory capacity and adenosine triphosphate production, which involves the Sirtuin3-NDUFA9 deacetylation.
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http://dx.doi.org/10.1097/CCM.0000000000005268DOI Listing
September 2021

UAMC-3203 OR/and Deferoxamine Improve Post-Resuscitation Myocardial Dysfunction Through Suppressing Ferroptosis In A Rat Model of Cardiac Arrest.

Shock 2021 Oct 5. Epub 2021 Oct 5.

School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan Province, China School of Medicine, Anhui University of Science & Technology, Huainan, Anhui Province, China Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, Virginia Third People's Hospital of Chengdu Affiliated to Southwest Jiaotong University, Chengdu, Sichuan Province, China Departments of Internal Medicine and Emergency Medicine, Virginia Commonwealth University Health System, Richmond, Virginia Department of Emergency Medicine, Virginia Commonwealth University Health System, Richmond, Virginia.

Abstract: Blocking ferroptosis reduces ischemia-reperfusion injury in some pathological contexts. However, there is no evidence that ferroptosis contributes to post-resuscitation myocardial dysfunction (PRMD). Here, we evaluated the therapeutic performance of ferroptosis inhibitors (UAMC-3203 or/and Deferoxamine) on the PRMD in a rat model of cardiac arrest and surveyed the changes of essential ferroptosis markers in the myocardium. Remarkably, all treatments reduce the severity of cardiac dysfunction and microcirculation hypoperfusion after resuscitation compared with control. Consistently, we observe that the ferroptosis marker Glutathione peroxidase 4, 4-hydroxynonenal and non-heme iron altered (1 ± 0.060 vs. 0.021 ± 0.016, 1 ± 0.145 vs. 3.338 ± 0.221, 52.010 ± 3.587 ug/g vs. 70.500 ± 3.158 ug/g, all P < 0.05) in the myocardium after resuscitation. These changes were significantly suppressed by UAMC-3203 [(0.187 ± 0.043, 2.848 ± 0.169, all P < 0.05), (72.43 ± 4.920 ug/g, P  > 0.05)], or Deferoxamine (0.203 ± 0.025, 2.683 ± 0.273, 55.95 ± 2.497 ug/g, all P < 0.05). Briefly, UAMC-3203 or/and Deferoxamine improve post-resuscitation myocardial dysfunction and provide evidence of ferroptosis involvement, suggesting that ferroptosis inhibitors could potentially provide an innovative therapeutic approach for mitigating the myocardial damage caused by cardiopulmonary resuscitation.
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http://dx.doi.org/10.1097/SHK.0000000000001869DOI Listing
October 2021

The E3 ubiquitin ligase TRIM31 plays a critical role in hypertensive nephropathy by promoting proteasomal degradation of MAP3K7 in the TGF-β1 signaling pathway.

Cell Death Differ 2021 Sep 28. Epub 2021 Sep 28.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Renal fibrosis and inflammation are critical for the initiation and progression of hypertensive renal disease (HRD). However, the signaling mechanisms underlying their induction are poorly understood, and the role of tripartite motif-containing protein 31 (TRIM31), an E3 ubiquitin ligase, in HRD remains unclear. This study aimed to elucidate the role of TRIM31 in the pathogenesis of HRD, discover targets of TRIM31, and explore the underlying mechanisms. Pathological specimens of human HRD kidney were collected and an angiotensin II (AngII)-induced HRD mouse model was developed. We found that TRIM31 was markedly reduced in both human and mouse HRD renal tissues. A TRIM31 mice was thus constructed and showed significantly aggravated hypertension-induced renal dysfunction, fibrosis, and inflammation, following chronic AngII infusion compared with TRIM31 mice. In contrast, overexpression of TRIM31 by injecting adeno-associated virus (AAV) 9 into C57BL/6J mice markedly ameliorated renal dysfunction, fibrotic and inflammatory response in AngII-induced HRD relative to AAV-control mice. Mechanistically, TRIM31 interacted with and catalyzed the K48-linked polyubiquitination of lysine 72 on Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), followed by the proteasomal degradation of MAP3K7, which further negatively regulated TGF-β1-mediated Smad and MAPK/NF-κB signaling pathways. In conclusion, this study has demonstrated for the first time that TRIM31 serves as an important regulator in AngII-induced HRD by promoting MAP3K7 K48-linked polyubiquitination and inhibiting the TGF-β1 signaling pathway.
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http://dx.doi.org/10.1038/s41418-021-00874-0DOI Listing
September 2021

[Characteristics and Health Risk Assessment of Heavy Metals in PM Under Winter Haze Conditions in Central China: A Case Study of Huanggang, Hubei Province].

Huan Jing Ke Xue 2021 Oct;42(10):4593-4601

School of Environmental Studies, China University of Geosciences, Wuhan 430074, China.

To explore the pollution characteristics and potential health risks of heavy metals in PM on haze days in Central China, PM samples were collected from the Huanggang monitoring station, a regional observation point in Central China, between January 13 and 24, 2018. The contents of Cr, Mn, Co, Ni, Cu, Zn, As, Cd, Sn, and Pb in PM were analyzed by inductively coupled plasma mass spectrometry(ICP-MS), and the enrichment factor method was used to determine the potential risk based on the exposure model recommended by the Environmental Protection Administration(EPA). The results showed that during the observation period, the concentrations of Zn in PM were highest, and the concentrations of the carcinogens As and Cd were higher than the secondary standard limits of China's ambient air quality standard(GB 3095-2012), with 70% of these elemental concentrations accounting for the largest proportion in the middle haze period. The enrichment factor analysis showed that Cd, Sn, Co, Pb, and Zn were the most abundant elements, especially during the middle haze period, and were mostly derived from transportation and coal combustion. The results of the human health risk assessment showed that exposure via hand-mouth feeding was the main non-carcinogenic risk, and the exposure and non-carcinogenic risks of children were significantly higher than those of adults. Pb poses a non-carcinogenic risk to children, while heavy metals in PM pose no non-carcinogenic risks to adults and carcinogenic heavy metals pose no carcinogenic risks.
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http://dx.doi.org/10.13227/j.hjkx.202101183DOI Listing
October 2021

Interprotomer disulfide-stabilized variants of the human metapneumovirus fusion glycoprotein induce high titer-neutralizing responses.

Proc Natl Acad Sci U S A 2021 09;118(39)

Vaccine Research Center, NIH, Bethesda, MD 20892;

Human metapneumovirus (HMPV) is a major cause of respiratory disease worldwide, particularly among children and the elderly. Although there is no licensed HMPV vaccine, promising candidates have been identified for related pneumoviruses based on the structure-based stabilization of the fusion (F) glycoprotein trimer, with prefusion-stabilized F glycoprotein trimers eliciting significantly higher neutralizing responses than their postfusion F counterparts. However, immunization with HMPV F trimers in either prefusion or postfusion conformations has been reported to elicit equivalent neutralization responses. Here we investigate the impact of stabilizing disulfides, especially interprotomer disulfides (IP-DSs) linking protomers of the F trimer, on the elicitation of HMPV-neutralizing responses. We designed F trimer disulfides, screened for their expression, and used electron microscopy (EM) to confirm their formation, including that of an unexpected postfusion variant. In mice, IP-DS-stabilized prefusion and postfusion HMPV F elicited significantly higher neutralizing responses than non-IP-DS-stabilized HMPV Fs. In macaques, the impact of IP-DS stabilization was more measured, although IP-DS-stabilized variants of either prefusion or postfusion HMPV F induced neutralizing responses many times the average titers observed in a healthy human cohort. Serological and absorption-based analyses of macaque responses revealed elicited HMPV-neutralizing responses to be absorbed differently by IP-DS-containing and by non-IP-DS-containing postfusion Fs, suggesting IP-DS stabilization to alter not only the immunogenicity of select epitopes but their antigenicity as well. We speculate the observed increase in immunogenicity by IP-DS trimers to be related to reduced interprotomer flexibility within the HMPV F trimer.
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http://dx.doi.org/10.1073/pnas.2106196118DOI Listing
September 2021

Spatiotemporal evolution analysis of NO column density before and after COVID-19 pandemic in Henan province based on SI-APSTE model.

Sci Rep 2021 09 20;11(1):18614. Epub 2021 Sep 20.

Henan Engineering Laboratory of Spatial Information Processing, Henan Key Laboratory of Big Data Analysis and Processing, School of Computer and Information Engineering, Henan University, Kaifeng, 475004, People's Republic of China.

Air pollution is the result of comprehensive evolution of a dynamic and complex system composed of emission sources, topography, meteorology and other environmental factors. The establishment of spatiotemporal evolution model is of great significance for the study of air pollution mechanism, trend prediction, identification of pollution sources and pollution control. In this paper, the air pollution system is described based on cellular automata and restricted agents, and a Swarm Intelligence based Air Pollution SpatioTemporal Evolution (SI-APSTE) model is constructed. Then the spatiotemporal evolution analysis method of air pollution is studied. Taking Henan Province before and after COVID-19 pandemic as an example, the NO products of TROPOMI and OMI were analysed based on SI-APSTE model. The tropospheric NO Vertical Column Densities (VCDs) distribution characteristics of spatiotemporal variation of Henan province before COVID-19 pandemic were studied. Then the tropospheric NO VCDs of TROPOMI was used to study the pandemic period, month-on-month and year-on-year in 18 urban areas of Henan Province. The results show that SI-APSTE model can effectively analyse the spatiotemporal evolution of air pollution by using environmental big data and swarm intelligence, and also can establish a theoretical basis for pollution source identification and trend prediction.
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http://dx.doi.org/10.1038/s41598-021-97745-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452647PMC
September 2021

Modern lake sedimentary record of PAHs and OCPs in a typical karst wetland, south China: Response to human activities and environmental changes.

Environ Pollut 2021 Sep 14;291:118173. Epub 2021 Sep 14.

School of Environmental Studies & State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences, Wuhan, 430078, China.

The sedimentary history of polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) over the past 140 years in a lake sediment core from Huixian karst wetland was reconstructed. The total PAHs and OCPs concentrations ranged from 40.0 to 210 ng g and 0.98 to 31.4 ng g, respectively. The vertical distribution of PAHs and OCPs in different stages was great consistent with the history of regional socio-economic development and the usage of OCPs. As the indicators of socio-economic development, gross domestic product (GDP), population, energy consumption, highway mileage, and private vehicles correlated with the PAHs concentrations, indicating the impact of human activities on PAHs levels. The PAHs and OCPs concentrations were also affected by environmental changes in the wetland, as reconstructed by total organic carbon (TOC), sand, silt, clay, quartz, and calcite in sediments. Redundancy analysis (RDA) results showed TOC was the dominant factor to explain the concentrations of PAHs and OCPs with the explanation of 86.7% and 43.5%, respectively. In addition, TOC content had significantly positive correlation with PAHs (0.96, p < 0.01) and OCPs (0.78, p < 0.01). In particular, the significantly positive correlation (p < 0.05) between calcite and PAHs and OCPs inferred that karstification might play an important role in the migration of PAHs and OCPs in the karst area. Therefore, the lake in Huixian wetland tended to be a sink more than a source of PAHs and OCPs influenced by the increasing TOC content and karstification under climate warming.
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http://dx.doi.org/10.1016/j.envpol.2021.118173DOI Listing
September 2021

The incubation period of COVID-19: a global meta-analysis of 53 studies and a Chinese observation study of 11 545 patients.

Infect Dis Poverty 2021 Sep 17;10(1):119. Epub 2021 Sep 17.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou, 450001, Henan, People's Republic of China.

Background: The incubation period is a crucial index of epidemiology in understanding the spread of the emerging Coronavirus disease 2019 (COVID-19). In this study, we aimed to describe the incubation period of COVID-19 globally and in the mainland of China.

Methods: The searched studies were published from December 1, 2019 to May 26, 2021 in CNKI, Wanfang, PubMed, and Embase databases. A random-effect model was used to pool the mean incubation period. Meta-regression was used to explore the sources of heterogeneity. Meanwhile, we collected 11 545 patients in the mainland of China outside Hubei from January 19, 2020 to September 21, 2020. The incubation period fitted with the Log-normal model by the coarseDataTools package.

Results: A total of 3235 articles were searched, 53 of which were included in the meta-analysis. The pooled mean incubation period of COVID-19 was 6.0 days (95% confidence interval [CI] 5.6-6.5) globally, 6.5 days (95% CI 6.1-6.9) in the mainland of China, and 4.6 days (95% CI 4.1-5.1) outside the mainland of China (P = 0.006). The incubation period varied with age (P = 0.005). Meanwhile, in 11 545 patients, the mean incubation period was 7.1 days (95% CI 7.0-7.2), which was similar to the finding in our meta-analysis.

Conclusions: For COVID-19, the mean incubation period was 6.0 days globally but near 7.0 days in the mainland of China, which will help identify the time of infection and make disease control decisions. Furthermore, attention should also be paid to the region- or age-specific incubation period.
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http://dx.doi.org/10.1186/s40249-021-00901-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446477PMC
September 2021

Spatial and seasonal variations of PAHs in soil, air, and atmospheric bulk deposition along the plain to mountain transect in Hubei province, central China: Air-soil exchange and long-range atmospheric transport.

Environ Pollut 2021 Sep 10;291:118139. Epub 2021 Sep 10.

State Key Laboratory of Biogeology and Environmental Geology, School of Environmental Studies, China University of Geosciences, Wuhan, 430078, China. Electronic address:

Polycyclic aromatic hydrocarbons (PAHs) are a long-term environmental problem faced by human society. The sources of involuntary PAHs are complex, moreover, secondary emissions of fixed PAHs in the environment occur due to global change and disturbance of human activities. Samples of three environmental media including soil, air, and atmospheric bulk deposition were collected to observe the spatial distribution and seasonal variation, to discuss the source or sink of PAHs and their association with the air mass transport along the plain (Jianghan Plain, JHP) to mountain transect, and explore the geographic scope of the atmospheric transport influence. The results obtained showed that 16 individual PAHs generally existed in all environmental multimedia being studied, and the PAHs concentration in air, soil and deposition flux of atmospheric bulk was higher in JPH than in "Western Hubei Mountains" (WHMs). Considerably high PAHs concentrations were obtained from the soil, air and atmospheric bulk deposition in winter, summer, and both summer and winter, respectively. The air-soil fugacity fraction of PAHs indicated that the soil of Dajiuhu (DJH) is likely to be a sink. Backward air trajectory simulation confirmed that most of the air mass passes over the JHP before reaching DJH, combined with the (transport and persistence level III) TaPL3 model results JHP are acting as sources. However, seasonal changes lead to a shift in the roles of soil sources and sinks. The TaPL3 model calculated that PAHs are transported through water for a wider range of effects and a longer persistence, even up to 10 years.
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http://dx.doi.org/10.1016/j.envpol.2021.118139DOI Listing
September 2021

Deletion of natriuretic peptide receptor C alleviates adipose tissue inflammation in hypercholesterolemic Apolipoprotein E knockout mice.

J Cell Mol Med 2021 Oct 15;25(20):9837-9850. Epub 2021 Sep 15.

Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

The inflammation of adipose tissue is one of the most common secondary pathological changes in atherosclerosis, which in turn influences the process of atherosclerosis. Natriuretic peptides have been revealed important effect in regulating adipose metabolism. However, the relationship between natriuretic peptide receptor C and inflammation of adipose tissue in atherosclerosis remains unknown. This study aims to explore the effect natriuretic peptide receptor C exerts on the regulation of the adipose inflammation in atherosclerotic mice induced by western-type diet and its overlying mechanisms. To clarify the importance of NPRC of adipose inflammation in atherosclerotic mice, NPRC expression was measured in mice fed with chow diet and western-type diet for 12 weeks and we found a considerable increase in adipose tissue of atherosclerotic mice. Global NPRC knockout in mice was bred onto ApoE mice to generate NPRC ApoE mice, which displayed remarked increase in browning of white adipose tissue and lipolysis of adipose tissue and decrease in adipose inflammation manifested by decreased macrophage invasion to form less CLS (crown-like structure), reduced oxidative stress and alleviated expression of TNFα, IL-6, IL-1β and MCP1, but increased expression of adiponectin in adipose tissue. Moreover, our study showed that white adipose tissue browning in NPRC ApoE atherosclerotic mice was associated with decreased inflammatory response through cAMP/PKA signalling activation. These results identify NPRC as a novel regulator for adipose inflammation in atherosclerotic mice by modulating white adipose tissue browning.
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http://dx.doi.org/10.1111/jcmm.16931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505842PMC
October 2021

CircRNA_0026344 via miR-21 is involved in cigarette smoke-induced autophagy and apoptosis of alveolar epithelial cells in emphysema.

Cell Biol Toxicol 2021 Sep 15. Epub 2021 Sep 15.

Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China.

Cigarette smoke (CS), a main source of indoor air pollution, is a primary risk factor for emphysema, and aberrant cellular autophagy is related to the pathogenesis of emphysema. Circular RNAs (circRNAs) affect the expression of mRNAs via acting as microRNA (miRNA) sponges, but their role in emphysema progression is not established. In the present investigation, CS, acting on alveolar epithelial cells, caused higher levels of miR-21, p-ERK, and cleaved-caspase 3 and led to lower levels of circRNA_0026344 and PTEN, which induced autophagy and apoptosis. miR-21 suppressed the expression of PTEN, which was involved in the regulation of autophagy and apoptosis. Further, in alveolar epithelial cells, overexpression of circRNA_0026344 blocked cigarette smoke extract (CSE)-induced autophagy and apoptosis, but this blockage was reversed by upregulation of miR-21 with a mimic. These results demonstrated that, in alveolar epithelial cells, CS decreases circRNA_0026344 levels, which sponge miR-21 to inhibit the miR-21 target, PTEN, which, in turn, activates ERK and thereby promotes autophagy and apoptosis, leading to emphysema. Thus, for emphysema, circRNA_0026344 regulates the PTEN/ERK axis by sponging miR-21, which is associated with the CS-induced autophagy and apoptosis of alveolar epithelial cells. In sum, the present investigation identifies a novel mechanism for CS-induced emphysema and provides information useful for the diagnosis and treatment of CS-induced emphysema.
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http://dx.doi.org/10.1007/s10565-021-09654-5DOI Listing
September 2021

Angiotensin IV attenuates diabetic cardiomyopathy suppressing FoxO1-induced excessive autophagy, apoptosis and fibrosis.

Theranostics 2021 25;11(18):8624-8639. Epub 2021 Jul 25.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.

The rennin-angiotensin-aldosterone system (RAAS) plays a critical role in the pathogenesis of diabetic cardiomyopathy, but the role of a member of RAAS, angiotensin IV (Ang IV), in this disease and its underlying mechanism are unclear. This study was aimed to clarify the effects of Ang IV and its downstream mediator forkhead box protein O1 (FoxO1) on diabetic cardiomyopathy. , diabetic mice were treated with low-, medium- and high-dose Ang IV, ATR antagonist divalinal, FoxO1 inhibitor AS1842856 (AS), or their combinations. , H9C2 cardiomyocytes and cardiac fibroblasts were treated with different concentrations of glucose, low-, medium- and high-dose Ang IV, divalinal, FoxO1-overexpression plasmid (FoxO1-OE), AS, or their combinations. Ang IV treatment dose-dependently attenuated left ventricular dysfunction, fibrosis, and myocyte apoptosis in diabetic mice. Besides, enhanced autophagy and FoxO1 protein expression by diabetes were dose-dependently suppressed by Ang IV treatment. However, these cardioprotective effects of Ang IV were completely abolished by divalinal administration. Bioinformatics analysis revealed that the differentially expressed genes were enriched in autophagy, apoptosis, and FoxO signaling pathways among control, diabetes, and diabetes+high-dose Ang IV groups. Similar to Ang IV, AS treatment ameliorated diabetic cardiomyopathy in mice. , high glucose stimulation increased collagen expression, apoptosis, overactive autophagy flux and FoxO1 nuclear translocation in cardiomyocytes, and upregulated collagen and FoxO1 expression in cardiac fibroblasts, which were substantially attenuated by Ang IV treatment. However, these protective effects of Ang IV were completely blocked by the use of divalinal or FoxO1-OE, and these detrimental effects were reversed by the additional administration of AS. Ang IV treatment dose-dependently attenuated left ventricular dysfunction and remodeling in a mouse model of diabetic cardiomyopathy, and the mechanisms involved stimulation of ATR and suppression of FoxO1-mediated fibrosis, apoptosis, and overactive autophagy.
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http://dx.doi.org/10.7150/thno.48561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419053PMC
July 2021

Outcomes of pediatric patients with therapy-related myeloid neoplasms.

Bone Marrow Transplant 2021 Sep 3. Epub 2021 Sep 3.

Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.
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http://dx.doi.org/10.1038/s41409-021-01448-xDOI Listing
September 2021

High-resolution respirometry for evaluation of mitochondrial function on brain and heart homogenates in a rat model of cardiac arrest and cardiopulmonary resuscitation.

Biomed Pharmacother 2021 Oct 30;142:111935. Epub 2021 Aug 30.

Weil Institute of Emergency and Critical Care Research, Virginia Commonwealth University, Richmond, VA, USA; Department of Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA, USA. Electronic address:

The physiology and physiopathology process of mitochondrial function following cardiac arrest remains poorly understood. We aimed to assess mitochondrial respiratory function on the heart and brain homogenates from cardiac arrest rats. The expression level of SIRT1/PGC-1α pathway was measured by immunoblotting. 30 rats were assigned to the CA group and the sham group. Rats of CA were subjected to 6 min of untreated ventricular fibrillation (VF) followed by 8 min of cardiopulmonary resuscitation (CPR). Mitochondrial respiratory function was compromised following CA and I/R injury, as indicated by CI (451.46 ± 71.48 vs. 909.91 ± 5.51 pmol/min*mg for the heart and 464.14 ± 8.22 vs. 570.53 ± 56.33 pmol/min*mg for the brain), CI (564.04 ± 64.34 vs. 2729.52 ± 347.39 pmol/min*mg for the heart and 726.07 ± 85.78 vs. 1762.82 ± 262.04 pmol/min*mg for the brain), RCR (1.88 ± 0.46 vs. 3.57 ± 0.38 for the heart and 2.05 ± 0.19 vs. 3.49 ± 0.19, for the brain) and OXPHOS coupling efficiency (0.45 ± 0.11 vs. 0.72 ± 0.03 for the heart and 0.52 ± 0.05 vs. 0.71 ± 0.01 for the brain). However, routine respiration was lower in the heart and comparable in the brain after CA. CIV did not change in the heart but was enhanced in the brain. Furthermore, both SIRT1 and PGC-1α were downregulated concurrently in the heart and brain. The mitochondrial respiratory function was compromised following CA and I/R injury, and the major affected respiratory state is complex I-linked respiration. Furthermore, the heart and the brain respond differently to the global I/R injury after CA in mitochondrial respiratory function. Inhibition of the SIRT1/PGC-1α pathway may be a major contributor to the impaired mitochondrial respiratory function.
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http://dx.doi.org/10.1016/j.biopha.2021.111935DOI Listing
October 2021

Water Splitting with a Single-Atom Cu/TiO Photocatalyst: Atomistic Origin of High Efficiency and Proposed Enhancement by Spin Selection.

JACS Au 2021 May 26;1(5):550-559. Epub 2021 Apr 26.

Department of Chemistry, University of Southern California, Los Angeles, California 90089, United States.

Anatase TiO is an intensely investigated photocatalytic material due to its abundance and chemical stability. However, it suffers from weak light harvesting and low photocatalytic efficiency. Experiments show that light absorption and photocatalytic properties can be enhanced simultaneously by TiO doping with well-dispersed Cu atoms, forming a single-atom catalyst (Cu/TiO) that can be used for solar water splitting and other applications. By performing ab initio nonadiabatic molecular dynamics simulations, we demonstrate that Cu/TiO is inactive before light irradiation due to rapid electron-hole recombination via both shallow and deep traps. Surprisingly, the shallow trap is more detrimental to the Cu/TiO performance than the deep trap because it couples better to free carriers. After light irradiation, leading to electron transfer and Cu/TiO protonation, the shallow trap is eliminated, and a local distortion around the Cu atom stabilizes the deep trap state on the Cu d-orbital, decoupling it from free charges and giving rise to high photocatalytic hydrogen generation activity. We further demonstrate that the photocatalytic performance of Cu/TiO can be enhanced by spin selection, achievable experimentally via optical intersite spin transfer or chiral semiconductor coating. Both H adsorption and spin selection enhance charge carrier lifetimes by an order of magnitude. The spin selection mechanism does not require formation of the H species, which necessitates concurrent sources of electrons and protons and which is intrinsically unstable because water splitting involves frequent proton shuffling. Our results rationalize the experimental observations at the atomistic level, provide mechanistic insights into operation of single atom photocatalysis, and demonstrate that spin selection can be used to develop advanced and efficient systems for solar energy conversion.
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http://dx.doi.org/10.1021/jacsau.1c00004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395698PMC
May 2021

Hearing Loss in Neurological Disorders.

Front Cell Dev Biol 2021 11;9:716300. Epub 2021 Aug 11.

Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, China.

Sensorineural hearing loss (SNHL) affects approximately 466 million people worldwide, which is projected to reach 900 million by 2050. Its histological characteristics are lesions in cochlear hair cells, supporting cells, and auditory nerve endings. Neurological disorders cover a wide range of diseases affecting the nervous system, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), autism spectrum disorder (ASD), etc. Many studies have revealed that neurological disorders manifest with hearing loss, in addition to typical nervous symptoms. The prevalence, manifestations, and neuropathological mechanisms underlying vary among different diseases. In this review, we discuss the relevant literature, from clinical trials to research mice models, to provide an overview of auditory dysfunctions in the most common neurological disorders, particularly those associated with hearing loss, and to explain their underlying pathological and molecular mechanisms.
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http://dx.doi.org/10.3389/fcell.2021.716300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385440PMC
August 2021

Coping with Multiple Chronic Conditions in the Family Context: A Meta-Synthesis.

Authors:
Cheng Cheng Jie Bai

West J Nurs Res 2021 Aug 25:1939459211041171. Epub 2021 Aug 25.

Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

This study was to collect, synthesize, and interpret the current qualitative evidence from studies that investigated family coping among people with multiple chronic conditions (MCCs). A meta-synthesis approach was used to report this study. A systematic search was performed in five electronic databases, including CINAHL, EMBASE, PsycINFO, Web of Science, and PubMed from January 2000 to December 2020. The PRISMA flow chart and Joanna Briggs Institute Qualitative Assessment and Review Instrument checklist are integrated into the meta-synthesis. A total of ten eligible studies including data from 381 participants were identified. Three meta-themes were identified in the synthesis: (1) family role maintenance in MCCs management, (2) coping as a family, and (3) be frustrated with family interactions. This meta-synthesis indicated the importance of maintaining social roles and family support within family interactions for coping with MCCs. It also demonstrated the frustrations in the family coping process experienced by people with MCCs. Health care professionals should understand the interactions between people with MCCs and their family members that may impact people's coping. Such an understanding may contribute to the development of supportive programs such as family-based interventions for people with MCCs.
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http://dx.doi.org/10.1177/01939459211041171DOI Listing
August 2021

A quality evaluation of the clinical practice guidelines on breast cancer using the RIGHT checklist.

Ann Transl Med 2021 Jul;9(14):1174

Department of Internal Medicine, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Background: Breast cancer is the most frequent type of cancer in women. The methodological quality of clinical practice guidelines (CPGs) on breast cancer has been shown to be heterogeneous. The aim of our study was to evaluate the quality of breast cancer CPGs published in years 2018-2020, using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist.

Methods: We searched Medline (via PubMed), Chinese National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature (CBM) as well as websites of guideline organizations for CPGs on breast cancer published between 2018 and 2020. We used the RIGHT checklist to evaluate the reporting quality of the included guidelines by assessing whether the CPGs adhered to each item of the checklist and calculated the proportions of appropriately reported RIGHT checklist items. We also presented the adherence reporting rates for each guideline and the mean rates for each of the seven domains of the RIGHT checklist.

Results: A total of 45 guidelines were included. Eighteen (40.0%) guidelines had an overall reporting rate below 50% and only three (6.7%) reported more than 80% of the items. The domains "Basic information" and "Background" had the highest reporting rates (75.9% and 62.5%, respectively). The mean reporting rates of the domains "Evidence", "Recommendation", "Review and quality assurance", "Funding and declaration and management of interests" and "Other information" were 42.7%, 53.0%, 33.3%, 45.0%, and 44.4%, respectively.

Conclusions: The reporting quality varied among guidelines for breast cancer, showing the need for improvement in reporting the contents. Guideline developers should pay more attention to reporting the evidence, review and quality assurance, and funding and declaration and management of interests in future.
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http://dx.doi.org/10.21037/atm-21-2884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350626PMC
July 2021

Circular RNA circVRK1 suppresses the proliferation, migration and invasion of osteosarcoma cells by regulating zinc finger protein ZNF652 expression via microRNA miR-337-3p.

Bioengineered 2021 12;12(1):5411-5427

Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China.

Circular RNA is an innovative kind of endogenous non-coding RNA, which could take part in tumorigenesis. Nonetheless, the potential molecular mechanisms of circVRK1 in the progression of osteosarcoma remain unresolved. In the current study, we initially investigated circVRK1 levels in osteosarcoma clinical samples and cell lines by qRT-PCR analysis and northern blot assay. RNase R treatments, RNA stability assay and nucleoplasmic separation assay were conducted to identify the characteristics of circVRK1. We adopted CCK-8, colony formation, wound-healing, and transwell assays to assess the biological effects of circVRK1 on the proliferation, migration, and invasiveness of osteosarcoma cells in vitro. We then constructed a xenograft model in nude mice to confirm the suppressive role of circVRK1 in vivo. Moreover, dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were utilized to elucidate the underlying molecular mechanisms mediated by circVRK1. We demonstrated that circVRK1 was a stable circular transcript localized in the cytoplasm of osteosarcoma cells, and the down-regulation of circVRK1 in osteosarcoma tissues was related to poor outcome of patients. Meanwhile, over-expressed circVRK1 obviously restrained the growth, migration, and invasion of osteosarcoma in vitro and in vivo. Mechanistically, circVRK1 was assumed to be a microRNA sponge for miR-337-3p, and ZNF652 was the downstream gene of miR-337-3p. CircVRK1 overexpression or miR-337-3p knockdown accelerated ZNF652 expression, and up-regulated miR-337-3p efficiently abolished the promotion of ZNF652 induced by circVRK1. Moreover, rescue experiments have proved that circVRK1 inhibits the progression of osteosarcoma by modulating the miR-337-3p/ZNF652 axis. Therefore, we conclude that circVRK1 promotes ZNF652 expression by sponging miR-337-3p. CircVRK1 serves as a molecule sponge for miR-337-3p and mediates the ceRNA network to promote the expression of ZNF652, thus suppresses osteosarcoma proliferation, migration and invasion.
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http://dx.doi.org/10.1080/21655979.2021.1965695DOI Listing
December 2021

Association of Combined Focal 22q11.22 Deletion and IKZF1 Alterations With Outcomes in Childhood Acute Lymphoblastic Leukemia.

JAMA Oncol 2021 Oct;7(10):1521-1528

Division of Pediatric Hematology & Oncology, Department of Pediatrics, University of Utah, Salt Lake City.

Importance: Alterations in the IKZF1 gene drive B-cell acute lymphoblastic leukemia (B-ALL) but are not routinely used to stratify patients by risk because of inconsistent associations with outcomes. We describe a novel deletion in 22q11.22 that was consistently associated with very poor outcomes in patients with B-ALL with IKZF1 alterations.

Objective: To determine whether focal deletions within the λ variable chain region in chromosome 22q11.22 were associated with patients with B-ALL with IKZF1 alterations with the highest risk of relapse and/or death.

Design, Setting, And Participants: This cohort study included 1310 primarily high-risk pediatric patients with B-ALL who were taken from 6 independent clinical cohorts, consisting of 3 multicenter cohorts (AALL0232 [2004-2011], P9906 [2000-2003], and patients with Down syndrome who were pooled from national and international studies) and 3 single-institution cohorts (University of Utah [Salt Lake City], Children's Hospital of Philadelphia [Philadelphia, Pennsylvania], and St. Jude Children's Hospital [Memphis, Tennessee]). Data analysis began in 2011 using patients from the older studies first, and data analysis concluded in 2021.

Exposures: Focal 22q11.22 deletions.

Main Outcomes And Measures: Event-free and overall survival was investigated. The hypothesis that 22q11.22 deletions stratified the prognostic effect of IKZF1 alterations was formulated while investigating nearby deletions in VPREB1 in 2 initial cohorts (n = 270). Four additional cohorts were then obtained to further study this association (n = 1040).

Results: This study of 1310 patients with B-ALL (717 male [56.1%] and 562 female patients [43.9%]) found that focal 22q11.22 deletions are frequent (518 of 1310 [39.5%]) in B-ALL and inconsistent with physiologic V(D)J recombination. A total of 299 of 1310 patients with B-ALL had IKZF1 alterations. Among patients with IKZF1 alterations, more than half shared concomitant focal 22q11.22 deletions (159 of 299 [53.0%]). Patients with combined IKZF1 alterations and 22q11.22 deletions had worse outcomes compared with patients with IKZF1 alterations and wild-type 22q11.22 alleles in every cohort examined (combined cohorts: 5-year event-free survival rates, 43.3% vs 68.5%; hazard ratio [HR], 2.18; 95% CI, 1.54-3.07; P < .001; 5-year overall survival rates, 66.9% vs 83.9%; HR, 2.05; 95% CI, 1.32-3.21; P = .001). While 22q11.22 deletions were not prognostic in patients with wild-type IKZF1 , concomitant 22q11.22 deletions in patients with IKZF1 alterations stratified outcomes across additional risk groups, including patients who met the IKZF1plus criteria, and maintained independent significance in multivariate analysis for event-free survival (HR, 2.05; 95% CI, 1.27-3.29; P = .003) and overall survival (HR, 1.83; 95% CI, 1.01-3.34; P = .05).

Conclusions And Relevance: This cohort study suggests that 22q11.22 deletions identify patients with B-ALL and IKZF1 alterations who have very poor outcomes and may offer a new genetic biomarker to further refine B-ALL risk stratification and treatment strategies.
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http://dx.doi.org/10.1001/jamaoncol.2021.2723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377604PMC
October 2021

Photocatalytic overall water splitting without noble-metal: Decorating CoP on Al-doped SrTiO.

J Colloid Interface Sci 2021 Aug 11;606(Pt 1):491-499. Epub 2021 Aug 11.

International Research Center for Renewable Energy (IRCRE), State Key Laboratory of Multiphase Flow in Power Engineering (MFPE), Xi'an Jiaotong University (XJTU), 28 West Xianning Road, Xi'an 710049, China. Electronic address:

CoP, a noble-metal-free cocatalyst, was first introduced onto the surface of Al-doped SrTiO (Al:STO) via an in situ photodeposition-phosphorization method for photocatalytic overall water splitting (POWS) into stoichiometric H and O. Compared with pure Al:STO, the POWS activity was enhanced by a factor of ~ 421 over 1.0%CoP/Al:STO, with the highest evolution rates of 2106 and 1002 μmol h g for H and O, respectively. The mechanism for the remarkably boosted POWS activity was systematically analyzed based on the comprehensive characterization. On the one hand, benefiting from the in situ photodeposition process, CoP with metallic character were intimately decorated onto the surface of Al:STO and accelerated the separation and migration of photoinduced charge carriers. On the other hand, CoP, serving as reactive sites for H evolution reaction, lowered the overpotential and facilitated the surface reduction reaction, thereby enhancing the POWS activity. Furthermore, CrO was photodeposited on the surface of 1.0%CoP/Al:STO composite to suppress the undesired reverse reaction and the POWS activity was further enhanced up to 3558 and 1722 μmol h g for H and O, respectively, with apparent quantum yield of 7.1% at 350 ± 10 nm. This work presents a new avenue for designing POWS system without noble-metal cocatalyst.
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http://dx.doi.org/10.1016/j.jcis.2021.08.049DOI Listing
August 2021

15,16-dihydrotanshinone I inhibits EOMA cells proliferation by interfering in posttranscriptional processing of hypoxia-inducible factor 1.

Int J Med Sci 2021 11;18(14):3214-3223. Epub 2021 Jul 11.

Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Infantile hemangioma (IH), which threatens the physical and mental health of patients, is the most common benign tumor in infants. Previously, we found that 15,16-dihydrotanshinone I (DHTS) was significantly more effective at inhibiting hemangioma proliferation in vitro and in vivo than the first-line treatment propranolol. To investigate the underlying mechanism of DHTS, we used EOMA cells as a model to study the effect of DHTS. We compared the transcriptomes of control and DHTS-treated EOMA cells. In total, 2462 differentially expressed genes were detected between the groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed downregulated activity of the hypoxia-inducible factor 1 alpha (HIF-1α) signaling pathway in EOMA cells following treatment with DHTS. Thus, we investigated HIF-1α expression at protein and mRNA levels. Our results revealed that DHTS downregulated HIF-1α expression by interfering in its posttranscriptional processing, and the RNA-binding protein HuR participated in this mechanism. Our findings provide a basis for clinical transformation of DHTS and insight into pathogenic mechanisms involved in IH.
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http://dx.doi.org/10.7150/ijms.60774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364454PMC
July 2021

Plasma-activated thermosensitive biogel as an exogenous ROS carrier for post-surgical treatment of cancer.

Biomaterials 2021 09 9;276:121057. Epub 2021 Aug 9.

Department of Physics, Department of Materials Science and Engineering, And Department of Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.

Post-surgical residual tumor cells are the primary cause of relapse and progression of cancer but unfortunately, there are limited therapeutic options. In this work, a fillable plasma-activated biogel is produced on a thermosensitive biogel [(Poly-DL-lactide)-(poly-ethylene glycol)-(poly-DL-lactide), PLEL] with the aid of a discharge plasma for local post-operative treatment of cancer. In vivo data show that the plasma-activated PLEL biogel (PAPB) eliminates residual tumor tissues after removal surgery and also inhibits in situ recurrence while showing no evident systemic toxicity. Moreover, the PAPB possesses excellent storage capability, allows for slow release of plasma-generated reactive oxygen species (ROS), and exhibits good ROS-mediated anticancer effects in vitro. Our results reveal that the novel plasma-activated biogel is an effective therapeutic agent for local post-operative treatment of cancer.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121057DOI Listing
September 2021
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