Publications by authors named "Xiaohui Zhao"

308 Publications

HIGH CROSSOVER RATE1 encodes PROTEIN PHOSPHATASE X1 and restricts meiotic crossovers in Arabidopsis.

Nat Plants 2021 Apr 12. Epub 2021 Apr 12.

Department of Plant Sciences, University of Cambridge, Cambridge, UK.

Meiotic crossovers are tightly restricted in most eukaryotes, despite an excess of initiating DNA double-strand breaks. The majority of plant crossovers are dependent on class I interfering repair, with a minority formed via the class II pathway. Class II repair is limited by anti-recombination pathways; however, similar pathways repressing class I crossovers have not been identified. Here, we performed a forward genetic screen in Arabidopsis using fluorescent crossover reporters to identify mutants with increased or decreased recombination frequency. We identified HIGH CROSSOVER RATE1 (HCR1) as repressing crossovers and encoding PROTEIN PHOSPHATASE X1. Genome-wide analysis showed that hcr1 crossovers are increased in the distal chromosome arms. MLH1 foci significantly increase in hcr1 and crossover interference decreases, demonstrating an effect on class I repair. Consistently, yeast two-hybrid and in planta assays show interaction between HCR1 and class I proteins, including HEI10, PTD, MSH5 and MLH1. We propose that HCR1 plays a major role in opposition to pro-recombination kinases to restrict crossovers in Arabidopsis.
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http://dx.doi.org/10.1038/s41477-021-00889-yDOI Listing
April 2021

College Students' Perceptions About Prescription Drug Misuse Among Peers.

Am Health Drug Benefits 2021 Mar;14(1):29-38

Associate Professor, Department of Pharmaceutical Systems and Policy, School of Pharmacy, West Virginia University, Morgantown.

Background: Prescription drug misuse is an escalating public health problem that is prevalent among college students. Various factors, such as sex, age, race, mental health conditions, and fraternity and sorority membership, increase the risk for prescription drug misuse. Peer influences may also pose significant risks for starting prescription drug misuse, because peers are the primary source of misused prescription drugs among college students.

Objectives: To examine college students' beliefs about prescription drug misuse among their peers and to understand their beliefs about the available and potential intervention efforts to reduce prescription drug misuse.

Method: We conducted a cross-sectional survey of 312 college students aged 18 to 30 years who were enrolled in a large midwestern US university. The survey included questions about the responders' demographic characteristics, beliefs, and perceptions regarding prescription drug misuse among their peers and potential reduction programs for prescription drug misuse.

Results: The respondents' mean age was 21 years, and most (65%) respondents were women. A majority (90%) of the respondents were enrolled in the university as full-time students. More than 60% of the respondents reported knowing someone with prescription drug misuse in the past 12 months. Fraternity or sorority members were more likely to report peer prescription drug misuse than nonmembers (83% vs 60%, respectively; = .017). Stimulants were the most misused drug class, accounting for 75% of all reported peer prescription drug misuse. Approximately 60% of the misused prescription drugs were sourced from peers, which included friends, roommates, and classmates. A total of 73% of respondents said that prescription drug misuse was a problem among college students and 67% agreed that interventions were needed to reduce prescription drug misuse. The perceived need for interventions varied by peer prescription drug misuse. A total of 90% of students whose peers did not misuse prescription drugs said that interventions were needed, but only 67% of those with peer prescription drug misuse thought that interventions were needed.

Conclusion: Our findings indicate that peer prescription drug misuse is very common among college students, and the most misused drug class is stimulants. Survey respondents perceived that the current interventions used to address prescription drug misuse are not very effective or may not be targeting the right population. Peer prescription drug misuse influences college students' perceptions about the risks and harms of prescription drug misuse, as well as the need for interventions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025926PMC
March 2021

Stress and psychological impact of the COVID-19 outbreak on the healthcare staff at the fever clinic of a tertiary general hospital in Beijing: a cross-sectional study.

BJPsych Open 2021 Apr 5;7(3):e76. Epub 2021 Apr 5.

Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, China.

Background: It is important to maintain the psychological well-being of front-line healthcare staff during the coronavirus disease 2019 (COVID-19) pandemic.

Aims: To examine COVID-19-related stress and its immediate psychological impact on healthcare staff.

Method: All healthcare staff working in the fever clinic, from 20 January 2020 to 26 March 2020, of a tertiary general hospital were enrolled. Stress management procedures were in place to alleviate concerns about the respondents' own health and the health of their families, to help them adjust their work and to provide psychological support via a hotline. Qualitative interviews were undertaken and the Sources of Distress and the Impact of Event Scale-Revised (IES-R) were administered.

Results: Among the 102 participants (25 males; median age 30 years, interquartile range (IQR) = 27-36), the median IES-R total score was 3 (IQR = 0-8), and 6 participants (6.0%) scored above the cut-off on the IES-R (≥20). Safety and security were acceptable or better for 92 (90.2%) participants. The top four sources of distress were worry about the health of one's family/others at 0.88 (IQR = 0.25-1.25), worry about the virus spread at 0.50 (IQR = 0.00-1.00), worry about changes in work at 0.50 (IQR = 0.00-1.00) and worry about one's own health at 0.25 (IQR = 0.25-0.75). There was a moderate correlation between the IES-R score and the Sources of Distress score (rho = 0.501, P = 0.001).

Conclusions: The stress levels of healthcare staff in the fever clinic during the COVID-19 epidemic were not elevated. Physio-psychosocial interventions, including fulfilment of basic needs, activation of self-efficacy and psychological support, are helpful and worth recommending in fighting COVID-19.
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http://dx.doi.org/10.1192/bjo.2021.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027548PMC
April 2021

Mannose-Functionalized Biodegradable Nanoparticles Efficiently Deliver DNA Vaccine and Promote Anti-tumor Immunity.

ACS Appl Mater Interfaces 2021 Mar 22;13(12):14015-14027. Epub 2021 Mar 22.

Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, Queensland 4072, Australia.

Cancer vaccines have attracted increasing attention for their application in tumor immunotherapy. DNA vaccines are one of them that have been proven very promising with the advantages of safety, rapid design, and low cost. However, the low stability, ineffective cell internalization, and low immunostimulation hinder their wide application. Thus, developing targeted and safe systems to effectively deliver DNA vaccines becomes a vital step. In this study, we report the development of mannose- and bisphosphonate (BP)-modified calcium phosphate (CP) nanoparticles (NPs) as efficient vaccine delivery vehicles by targeting C-type lectin receptors (CLRs) on antigen-presenting cells (APCs). Using a model antigen ovalbumin (OVA)-encoded plasmid DNA (pOVA) as a model vaccine, we demonstrate that mannose-modified and BP-stabilized CP (MBCP) nanoparticles are mono-dispersed for enhanced uptake by APCs and subsequently induce OVA antigen presentation and immunostimulation. Mice immunized with MBCP-pOVA nanovaccines show a significantly stronger anti-OVA antibody response with a quicker IgG1 and IgG2a antibody production than unmodified NPs. Moreover, MBCP-pOVA immunization significantly inhibits the growth of OVA-expressing E.G7 tumor cells in C57BL/6J mice. Our data collectively suggest that the modifications to enhance the stability and targeting ability of MBCP NPs are essential for effective delivery of DNA vaccines and promote robust anti-tumor immunity.
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http://dx.doi.org/10.1021/acsami.1c01401DOI Listing
March 2021

Clinical significance of evaluation of collateral circulation in short-term prognosis of wake-up stroke patients.

Adv Clin Exp Med 2021 Feb;30(2):183-188

Department of Neurology, Pudong New Area People's Hospital, Shanghai, China.

Background: In recent years, the clinical significance of collateral circulation in vascular embolism has been gradually found.

Objectives: To investigate the relationship between collateral circulation and short-term prognosis of wake-up stroke patients.

Material And Methods: The present observational study enrolled 269 cases of wake-up ischemic stroke patients. All patients presented with mismatched low perfusion volume/main infraction volume and received thrombolytic therapy after admission. The hemorrhagic transformation rate was recorded. The American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading was used for evaluation of collateral circulation. The stroke condition was determined using the National Institutes of Health Stroke Scale (NIHSS). The Barthel Index (BI) score was used for measurement of quality of life. The Modified Rankin Scale (mRS) was used for measurement of prognosis.

Results: The hypertension, diabetes and current smoker rates were significantly higher. The baseline NHISS scores and NIHSS scores after 24 h were remarkably lower. The NIHSS scores were markedly lower in ASITN/SIR grade 2-3 patients compared with ASITN/SIR grade 0-1 patients at 1 week, 2 weeks, 4 weeks, and 3 months after treatment. Patients with ASITN/SIR grade 2-3 had lower mRS score and higher BI scores. The ASITN/SIR grade was an independent risk factor for bad prognosis of wake-up ischemic stroke patients in 3 months.

Conclusions: Collateral circulation condition may be associated with short-term prognosis of wake-up stroke patients. Patients with worse collateral circulation may present higher risk for bad short-term prognosis.
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http://dx.doi.org/10.17219/acem/121927DOI Listing
February 2021

Reversing Bacterial Resistance to Gold Nanoparticles by Size Modulation.

Nano Lett 2021 Mar 22;21(5):1992-2000. Epub 2021 Feb 22.

Department of Biomedical Engineering, Shenzhen Bay Laboratory, Southern University of Science and Technology, No. 1088, Xueyuan Road, Xili, Nanshan District, Shenzhen, Guangdong 518055, P. R. China.

One major frustration in developing antibiotics is that bacteria can quickly develop resistance that would require an entirely new cycle of research and clinical testing to overcome. Although plenty of bactericidal nanomaterials have been developed against increasingly severe superbugs, few reports have studied the resistance to these nanomaterials. Herein, we show that antibacterial 4,6-diamino-2-pyrimidine thiol (DAPT)-capped gold nanoparticles (AuDAPTs) can induce a 16-fold increased minimum inhibitory concentration (MIC) of only after very long term exposure (183 days), without developing cross-resistance to commercialized antibiotics. Strikingly, we recovered the bactericidal activities of AuDAPTs to the resistant strain by tuning the sizes of AuDAPTs without employing new chemicals. Such slow, easy-to-handle resistance induced by AuDAPTs is unprecedented compared to traditional antibiotics or other nanomaterials. In addition to the novel antibacterial activities and biocompatibilities, our approach will accelerate the development of gold nanomaterial-based therapeutics against multi-drug-resistant (MDR) bacterial infections.
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http://dx.doi.org/10.1021/acs.nanolett.0c04451DOI Listing
March 2021

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) may be safe for COVID-19 patients.

BMC Infect Dis 2021 Jan 25;21(1):114. Epub 2021 Jan 25.

The Department of Cardiovascular Surgery, Dalian Municipal Central Hospital, Dalian Medical University, Dalian, China.

Background: To investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) administration to hypertension patients with the coronavirus disease 2019 (COVID-19) induced pneumonia.

Methods: We recorded the recovery status of 67 inpatients with hypertension and COVID-19 induced pneumonia in the Raytheon Mountain Hospital in Wuhan during February 12, 2020 and March 30, 2020. Patients treated with ACEI or ARBs were categorized in group A (n = 22), while patients who were not administered either ACEI or ARBs were categorized into group B (n = 45). We did a comparative analysis of various parameters such as the pneumonia progression, length-of-stay in the hospital, and the level of alanine aminotransferase (ALT), serum creatinine (Cr), and creatine kinase (CK) between the day when these patients were admitted to the hospital and the day when the treatment ended.

Results: These 67 hypertension cases counted for 33.17% of the total COVID-19 patients. There was no significant difference in the usage of drug treatment of COVID-19 between groups A and B (p > 0.05). During the treatment, 1 case in group A and 3 cases in group B progressed from mild pneumonia into severe pneumonia. Eventually, all patients were cured and discharged after treatment, and no recurrence of COVID-2019 induced pneumonia occurred after the discharge. The length of stays was shorter in group A as compared with group B, but there was no significant difference (p > 0.05). There was also no significant difference in other general parameters between the patients of the groups A and B on the day of admission to the hospital (p > 0.05). The ALT, CK, and Cr levels did not significantly differ between groups A and B on the day of admission and the day of discharge (p > 0.05).

Conclusions: To treat the hypertension patients with COVID-19 caused pneumonia, anti-hypertensive drugs (ACEs and ARBs) may be used according to the relative guidelines. The treatment regimen with these drugs does not need to be altered for the COVID-19 patients.
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http://dx.doi.org/10.1186/s12879-021-05821-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829637PMC
January 2021

Effects of Ultrasonic Surface Rolling Processing and Subsequent Recovery Treatment on the Wear Resistance of AZ91D Mg Alloy.

Materials (Basel) 2020 Dec 14;13(24). Epub 2020 Dec 14.

Key Laboratory of Automobile Materials, School of Materials Science and Engineering, Jilin University, 5988 Renmin Street, Changchun 130025, China.

AZ91D Mg alloy was treated by ultrasonic surface rolling processing (USRP) and subsequent recovery treatment at different temperatures. The dry sliding friction test was performed to investigate the effects of USRP and subsequent recovery treatment on the wear resistance of AZ91D Mg alloy by a ball-on-plate tribometer. The microstructure, properties of plastic deformation layer and worn morphology were observed by optical microscope (OM), scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD) analysis and microhardness tester. Results illustrate that the grains of AZ91D Mg alloy surface layer are refined to nanocrystallines. The maximum microhardness of the top surface of the USRP sample reaches 102.3 HV. When USRP samples are treated by recovery treatment at 150 °C, 200 °C and 250 °C, the microhardness of the top surface decreases to 90.68 HV, 79.29 HV and 75.06 HV, respectively. The friction coefficient (FC) and wear volume loss of the USRP-R-150 sample are the lowest among all the samples. The worn surface morphology of the USRP-R-150 sample is smoother than that of other samples, indicating that the wear resistance of AZ91D Mg alloy treated by USRP and recovery treatment at 150 °C is improved significantly.
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http://dx.doi.org/10.3390/ma13245705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765076PMC
December 2020

High-power, low-coherence laser driver facility.

Opt Lett 2020 Dec;45(24):6839-6842

We report the first (to the best of our knowledge) high-power, low-coherence Nd:glass laser delivering kilojoule pulses with a coherent time of 249 fs and a bandwidth of 13 nm, achieving the 63%-efficiency second-harmonic conversion of the large-aperture low-coherence pulse and good beam smoothing effect. It provides a new type of laser driver for laser plasma interaction and high energy density physics research.
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http://dx.doi.org/10.1364/OL.412197DOI Listing
December 2020

Brachytherapy-based radiotherapy is associated with improved survival for newly diagnosed metastatic cervical cancer.

Brachytherapy 2021 Mar-Apr;20(2):361-367. Epub 2020 Dec 11.

Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China. Electronic address:

Purpose: The purpose of this study was to explore the value of brachytherapy (BT) in metastatic cervical cancer, as it has not been well evaluated before.

Methods And Materials: We analyzed 2391 patients with Stage IVB cervical cancer from 2004 to 2015 by using data from the Surveillance, Epidemiology, and End Results registry. The parameters were analyzed by Kaplan-Meier and Cox proportional hazards regression models to evaluate cancer-specific survival (CSS) and overall survival.

Results: In general, both univariate and multivariate analysis showed that age, histologic type, tumor size, and chemotherapy were associated with CSS and overall survival (p < 0.05). Further subgroup analysis showed BT alone or BT combined with external beam radiotherapy improved CSS despite the tumor size. In addition, chemotherapy and chemoradiotherapy prolonged CSS compared with external beam radiotherapy alone or no chemotherapy or radiotherapy independently of tumor size (p < 0.05).

Conclusions: For newly diagnosed metastatic cervical cancers, BT with or without external beam radiotherapy is associated with improved survival. As an aggressive option, chemoradiotherapy is also a potential treatment strategy.
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http://dx.doi.org/10.1016/j.brachy.2020.11.001DOI Listing
December 2020

Identification of phenolic compounds in fruits of Ribes stenocarpum Maxim. By UHPLC-QTOF/MS and their hypoglycemic effects in vitro and in vivo.

Food Chem 2021 May 22;344:128568. Epub 2020 Nov 22.

Qinghai Provincial Key Laboratory of Tibetan Medicine Research and Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, CAS, Qinghai 810008, China. Electronic address:

The gooseberry (Ribes stenocarpum Maxim. (CBZ)) is a wild and noncommercially cultivated berry fruit widely distributed in the Tibetan Plateau. The phenolic constituents from the berry fruit of CBZ were firstly identified by employing UPLC-QTOF MS. A total of 41 compounds, including hydroxycinnamic acids, hydroxybenzoic acids, flavonols and dihydroflavonol, were identified in view of their molecular weight, characteristic fragment ions and retention times. Further in vitro enzyme assay indicated that CBZ fruit extract could strongly and effectively inhibited a-glucosidase and α-amylase, with the IC values of 0.013 mg/mL and 0.005 mg/mL, respectively. In addition, the starch/maltose/sucrose tolerance experiment demonstrated that the CBZ fruit extract could reduce the sucrose mediated postprandial blood glucose (PBG) levels in normal mice, and significantly lower starch/maltose/ sucrose mediated PBG levels in diabetic mice. These results suggested that this berry fruit could be used as a dietary supplement, or drug for the control of hyperglycemia.
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http://dx.doi.org/10.1016/j.foodchem.2020.128568DOI Listing
May 2021

Different acetonitrile degraders and degrading genes between anaerobic ammonium oxidation and sequencing batch reactor as revealed by stable isotope probing and magnetic-nanoparticle mediated isolation.

Sci Total Environ 2021 Mar 11;758:143588. Epub 2020 Nov 11.

School of Environment, Tsinghua University, Beijing 100084, China; National Engineering Laboratory for Site Remediation Technologies, Beijing 100015, China. Electronic address:

Microbial degraders play crucial roles in wastewater treatment processes, but their use is limited as most microbes are yet unculturable. Stable isotope probing (SIP) is a cultivation-independent technique identifying functional-yet-uncultivable microbes in ambient environment, but is unsatisfactory for substrates with low assimilation rate owing to the low isotope incorporation into DNA. In this study, we used acetonitrile as the target low-assimilation chemical in many wastewater treatment plants and attempted to identify the active acetonitrile degraders in the activated sludge, via DNA-SIP and magnetic-nanoparticle mediated isolation (MMI) which is another cultivation-independent approach without the requirement of substrate labeling. The two approaches identified different active acetonitrile degraders in a 3-day short-term anaerobic ammonium oxidation (ANAMMOX). MMI enriched significantly more acetonitrile-degraders than SIP, showing the advantages in identifying the active degraders for low-assimilation substrates. Sequencing batch reactor (SBR, 30-day degradation) helped in more incorporation of N-labeled acetonitrile into the active degraders, thus the same acetonitrile-degraders and acetonitrile-degrading genes were identified by SIP and MMI. Different acetonitrile degraders between ANAMMOX and SBR were attributed to the distinct hydrological conditions. Our study for the first time explored the succession of acetonitrile-degraders in wastewater and identified the active acetonitrile-degraders which could be further enriched for enhancing acetonitrile degradation performance. These findings provide new insights into the acetonitrile metabolic process in wastewater treatment plants and offer suggestive conclusions for selecting appropriate treatment strategy in wastewater management.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143588DOI Listing
March 2021

Research on Cognitive Function in Anxious Depression Patients in China.

J Affect Disord 2021 Feb 11;280(Pt A):121-126. Epub 2020 Nov 11.

Peking University Sixth Hospital (Institute of Mental Health), Beijing, China.

Background: This study aimed to evaluate cognitive function in patients with anxious depression.

Methods: This was a part of the "Objective Diagnostic Indicators and Individualized Drug Intervention of Major Depressive Disorder (MDD)" study. All participants, including patients with MDD and healthy controls (HCs), completed the 17-item Hamilton Depression Scale (HAMD) and the Hamilton Anxiety Scale (HAMA). Anxious depression was defined as a HAMD anxiety/somatization factor score ≥7. Cognitive function was assessed at baseline and at the end of week 8. HC cognitive function was assessed at baseline.

Results: A total of 1048 people were included in the analysis, including 328 patients in the anxious depression group (G1=328), 221 patients in the MDD without anxious depression group (G2=221), and 499 in the HC group (G3=499). There were significant differences in the HAMA at baseline (t=13.050, p<0.001), HAMD at baseline (t=16.722, p<0.001), and HAMA at weekend 8 (z=-3.477, p=0.001) between G1 and G2. Cognitive functioning on the Hopkins Verbal Learning Test-Revised (HVLT-R) (t=2.948, p=0.003) and the Brief Visual Memory Test-Revised (BVMT-R) (t=2.843, p=0.005) was better in G1 than in G2 at baseline. Cognitive functioning on the HVLT-R (OR=1.081, p=0.006) was better in G1 than in G2 at weekend 8. The Stroop-color-word test (SCWT) (OR=0.976, p=0.004) and the Continuous Performance Test (CPT) (OR=0.698, p=0.007) showed significant differences at baseline; however, after the acute treatment phase, there were no significant differences in executive function (assessed by SCWT) (p=0.148) or attention/vigilance (assessed by CPT) (p=0.416) between G1 and G3.

Conclusions: Patients with anxious depression have more severe depressive symptoms but better cognitive function, especially for verbal learning, compared with nonanxious depression patients. After the acute treatment phase, executive function and attention/vigilance in anxious depression patients may be remitted.
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http://dx.doi.org/10.1016/j.jad.2020.11.078DOI Listing
February 2021

Two-step system for image receiving in OAM-SK-FSO link.

Opt Express 2020 Oct;28(21):30520-30541

Turbulence resistance is a significant research area for orbital angular momentum shift keying-based free space optical communication (OAM-SK-FSO). We put forward a two-step combinational system to receive high fidelity image data from the atmospheric turbulence (AT) channels. Firstly, the AT-detector-based multi-CNN (ATDM-CNN) demodulator is proposed which is very different from the traditional single-CNN (S-CNN) demodulator. The AT detector detects the AT strength and then an AT-determined CNN-based demodulator is activated to recognize the incident OAM modes. Sufficient numeral simulations compare the recognition rates of ATDM-CNN and S-CNN. The results indicate a tremendous improvement owing to the ATDM-CNN demodulator. Base on the ATDM-CNN's significant advantage in OAM recognition, the significant optimization of image data quality is possible in the further correction. As an option, the residual information errors are corrected by jointly using the rank-order adaptive median filter (RAMF) and the very-deep super-resolution (VDSR) network with minor information loss in severe ATs. The data increase resulting from RAMF-VDSR is tested. In conclusion, the proposed two-step system can provide a much higher quality of receiving image data in the OAM-SK-FSO link.
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http://dx.doi.org/10.1364/OE.397892DOI Listing
October 2020

Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells.

J Exp Med 2021 Jan;218(1)

Department of Pathology, University of Cambridge, Cambridge, UK.

Hofbauer cells (HBCs) are a population of macrophages found in high abundance within the stroma of the first-trimester human placenta. HBCs are the only fetal immune cell population within the stroma of healthy placenta. However, the functional properties of these cells are poorly described. Aligning with their predicted origin via primitive hematopoiesis, we find that HBCs are transcriptionally similar to yolk sac macrophages. Phenotypically, HBCs can be identified as HLA-DR-FOLR2+ macrophages. We identify a number of factors that HBCs secrete (including OPN and MMP-9) that could affect placental angiogenesis and remodeling. We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal. Finally, we also identify a population of placenta-associated maternal macrophages (PAMM1a) that adhere to the placental surface and express factors, such as fibronectin, that may aid in repair.
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http://dx.doi.org/10.1084/jem.20200891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579740PMC
January 2021

Microbial community structure in the river sediments from upstream of Guanting Reservoir: Potential impacts of reclaimed water recharge.

Sci Total Environ 2021 Apr 3;766:142609. Epub 2020 Oct 3.

College of Water Resources and Civil Engineering, China Agricultural University, Beijing, China. Electronic address:

This work systematically investigated the microbial community structure in the river sediments from upstream of Guanting Reservoir, Beijing, China. A total of 6 wastewater treatment plants (WWTPs) locate along the main rivers connected to the reservoir. Water and sediment samples were collected at sites near the effluents of WWTPs (regarded as W groups) or at the upstream/downstream rivers (R groups) to reveal the roles of the reclaimed water recharge. Multivariate techniques including typical statistical analysis, redundancy analysis (RDA), nonmetric multidimensional scaling analysis, and molecular ecological network analysis were used to evaluate the results and their relationships. The representative C/N/P water parameters and concentrations of target organic contaminants kept stable for W and R sites, while the microbial community parameters varied greatly for two groups. The microbial population at W sites were higher but with a lower biological diversity (with a lower Shannon index) than that at R sites, indicating WWTPs greatly altered the microbial community structure at the local reach. RDA results revealed that total organic carbon (TOC) and organophosphorus pesticides (OPPs) were two dominant factors affecting the function and composition of microbial communities at the phylum level. The network analysis revealed that the microbes with the most interactions mainly from R sites and they had closer relationships with each other.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142609DOI Listing
April 2021

Reagents-Loaded, Automated Assay that Integrates Recombinase-Aided Amplification and Cas12a Nucleic Acid Detection for a Point-of-Care Test.

Anal Chem 2020 11 16;92(21):14846-14852. Epub 2020 Oct 16.

Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088, Xueyuan Rd., Xili, Nanshan District, Shenzhen, Guangdong 518055, P. R. China.

Point-of-care testing for nucleic acid that combines amplification and readout is in great demand. This report integrates recombinase-aided amplification (RAA) with the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a system in a centrifugal microfluidic point-of-care test. We overcome the difficulty in the integration of these two processes, which mainly lies in the fact that Cas12a can digest the template DNA. We further integrate all reagents into the centrifugal microfluidics to automate the entire process. The Cas12a-assisted straightforward microfluidic equipment for analysis of nucleic acid (CASMEAN) enables us to rapidly and conveniently detect nucleic acid within 1.5 h. An application for detecting confirms the excellent compatibility between RAA and the Cas12a system, which ensures the superior performance of CASMEAN, such as capabilities of point-of-care detection, high sensitivity, and high specificity. CASMEAN is a genetic detection platform with great potential.
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http://dx.doi.org/10.1021/acs.analchem.0c03883DOI Listing
November 2020

Automated leukocyte parameters are useful in the assessment of myelodysplastic syndromes.

Cytometry B Clin Cytom 2020 Oct 1. Epub 2020 Oct 1.

Department of Pathology, University of California, Irvine, Orange, California, USA.

Background: Study utility of seven automated VCS parameters (V-volume, C-conductivity and S-scatter) in leukocytes as an objective read-out of dysplasia in Myelodysplastic Syndromes (MDS).

Methods: Peripheral blood was analyzed by Beckman-Coulter DxH800 hematology analyzer in 43 patients with low-grade, high-grade MDS and 21 control individuals. The differences in mean (MN) and standard deviation (SD) of each parameter were examined. The optimal sensitivity and specificity to predict MDS were determined by statistical analysis.

Results: In neutrophils, all means of the light scatters were significantly lower in high-grade MDS than in the control group. Mean median angle light scatter (MN-MALS-NE) and mean upper median angle light scatter (MN-UMALS-NE) were significantly different between low-grade MDS and control patients. MN-MALS-NE as a MDS predictor revealed 63% sensitivity and 67% specificity with a cutoff value of ≤133. SDs of each parameter in neutrophils differed significantly among three groups. SD of neutrophil upper median angle light scatter (SD-UMALS-NE) had 77% sensitivity and 82% specificity (cutoff value of ≥11.16) to predict MDS.

Conclusions: MDS patients have a significant decrease with a linear trend in VCS parameters in neutrophils, indicating cell dysplasia. The degree of the heterogeneity measured by SD is the most predictive of MDS.
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http://dx.doi.org/10.1002/cyto.b.21947DOI Listing
October 2020

KCNQ1OT1 contributes to sorafenib resistance and programmed death‑ligand‑1‑mediated immune escape via sponging miR‑506 in hepatocellular carcinoma cells.

Int J Mol Med 2020 Nov 25;46(5):1794-1804. Epub 2020 Aug 25.

School of Medical Laboratory, Sanquan College of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.

Drug resistance and immune escape of tumor cells severely compromise the treatment efficiency of hepatocellular carcinoma (HCC). Long non‑coding RNA KCNQ1 overlapping transcript 1 (lncRNA KCNQ1OT1) has been shown to be involved in drug resistance in several cancers. The aim of the present study was to investigate the role of KCNQ1OT1 in sorafenib resistance and immune escape of HCC cells. Reverse transcription‑quantitative PCR analysis, western blotting and immunohistochemistry were performed to detect the expression of KCNQ1OT1, miR‑506 and programmed death‑ligand‑1 (PD‑L1). Cell Counting Kit‑8 assay, flow cytometry and Transwell assays were used to evaluate IC50 value, cell apoptosis and metastasis. ELISA was performed to detect the secretion of cytokines. Dual‑luciferase reporter assay was conducted to verify the targeting relationships between miR‑506 and KCNQ1OT1 or PD‑L1. KCNQ1OT1 and PD‑L1 were found to be upregulated and miR‑506 was downregulated in sorafenib‑resistant HCC tissues and cells. Furthermore, KCNQ1OT1 knockdown reduced the IC50 value of sorafenib, suppressed cell metastasis and promoted apoptosis in sorafenib‑resistant HCC cells. Moreover, KCNQ1OT1 knockdown changed the tumor microenvironment and T‑cell apoptosis in a sorafenib‑resistant HCC/T‑cell co‑culture model. In addition, it was demonstrated that KCNQ1OT1 functioned as a competing endogenous RNA of miR‑506 and increased PD‑L1 expression in sorafenib‑resistant HCC cells. miR‑506 inhibition abolished the effects of KCNQ1OT1 knockdown on sorafenib sensitivity, tumor growth, the tumor microenvironment and T‑cell apoptosis. In conclusion, KCNQ1OT1 knockdown inhibited sorafenib resistance and PD‑L1‑mediated immune escape by sponging miR‑506 in sorafenib‑resistant HCC cells.
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http://dx.doi.org/10.3892/ijmm.2020.4710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521583PMC
November 2020

Temperature Dependence of G and D' Phonons in Monolayer to Few-Layer Graphene with Vacancies.

Nanoscale Res Lett 2020 Sep 30;15(1):189. Epub 2020 Sep 30.

Hebei Key Laboratory of Optic-electronic Information and Materials, College of Physics Science & Technology, Hebei University, Baoding, 071002, People's Republic of China.

The defects into the hexagonal network of a sp-hybridized carbon atom have been demonstrated to have a significant influence on intrinsic properties of graphene systems. In this paper, we presented a study of temperature-dependent Raman spectra of G peak and D' band at low temperatures from 78 to 318 K in defective monolayer to few-layer graphene induced by ion C+ bombardment under the determination of vacancy uniformity. Defects lead to the increase of the negative temperature coefficient of G peak, with a value almost identical to that of D' band. However, the variation of frequency and linewidth of G peak with layer number is contrary to D' band. It derives from the related electron-phonon interaction in G and D' phonon in the disorder-induced Raman scattering process. Our results are helpful to understand the mechanism of temperature-dependent phonons in graphene-based materials and provide valuable information on thermal properties of defects for the application of graphene-based devices.
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http://dx.doi.org/10.1186/s11671-020-03414-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527399PMC
September 2020

Anti-rheumatoid arthritis effects of iridoid glucosides from Lamiophlomis rotata (Benth.) kudo on adjuvant-induced arthritis in rats by OPG/RANKL/NF-κB signaling pathways.

J Ethnopharmacol 2021 Feb 24;266:113402. Epub 2020 Sep 24.

Qinghai Provincial Key Laboratory of Tibetan Medicine Research and Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, CAS, Qinghai, 810008, China. Electronic address:

Ethnopharmacological Relevance: Lamiophlomisrotata (Benth.) Kudo. has been used to treat trauma bleeding, rheumatism, yellow water disease in traditional Chinese medicine.

Aim: The aim of this work was to evaluate the anti-rheumatoid arthritis (RA) activities and underlying mechanisms of the total iridoid glucosides (TIG) from Lamiophlomisrotata (Benth.) Kudo.

Methods: The chemical constituents of TIG was analyzed by high-performance liquid chromatography (HPLC) with seven reference compounds (penstemonoside, chlorotuberside, shanzhiside methyl ester, phloyoside, 7-epliamalbide, phlorigidoside C and lamalbide). The anti-rheumatoid arthritis effects of TIG were investigated by arthritis indexes and paw swelling degrees, as well as histopathological and Micro-CT analysis in adjuvant-induced arthritis (AIA) rats. The impacts of TIG on the level of inflammatory cytokines (IL-1β, TNF-α, IL-6, IFN-γ, IL-17 and IL-10), and the regulation of OPG/RANKL/NF-κB pathways were determined by the ELISA and western blot, respectively.

Results: TIG significantly reduced the arthritis indexes and paws swelling in AIA rats, attenuated the inflammation and bone destruction in joint tissues, reduced the generation of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, IFN-γ and IL-17, as well as increased the generation of anti-inflammatory cytokine IL-10 in serum. Moreover, TIG markedly inhibited the expression of p-IKK-α, p-IκB and p-p65, and decreased the ratio of OPG/RANKL in the synovial tissues.

Conclusion: TIG possessed significant anti-RA activities on adjuvant-induced arthritis, which might be ascribed to the regulation of inflammatory cytokines IL-1β, TNF-α, IL-6, IFN-γ IL-17 and IL-10, as well as inhibition of OPG/RANKL/NF-κB signaling pathways.
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http://dx.doi.org/10.1016/j.jep.2020.113402DOI Listing
February 2021

Effects of a High Dose of the Contrast Medium Iodixanol on Renal Function in Patients Following Percutaneous Coronary Intervention.

Angiology 2021 02 10;72(2):145-152. Epub 2020 Sep 10.

Institution of Cardiovascular Research, Xinqiao Hospital, 105785Third Military Medical University (Army Medical University), Chongqing, China.

Iodixanol is associated with lower rates of contrast-induced acute kidney injury (CI-AKI). However, the effects of high volumes of iodixanol on renal function after percutaneous coronary intervention (PCI) have not been fully elucidated. This study evaluates the effects of high-dose (>300 mL) iodixanol on renal function within 72 hours of PCI. We retrospectively reviewed 676 consecutive patients who received high-dose (>300 mL) iodixanol during PCI between October 2015 and December 2017 in 4 centers. Logistic regression analysis was used to identify significant independent predictors for CI-AKI. The incidence of CI-AKI was 3.5% (23/651). In patients administered 300 to 500 mL and >500 mL iodixanol, the incidence of CI-AKI was 3.9% and 1.7%, respectively. In patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m, the incidence of CI-AKI was 2.6%. In high-risk and very high-risk patients, stratified by the Mehran risk score, the incidence of CI-AKI was 3.3% and 4.3%, respectively. In patients received high-dose iodixanol (>300 mL), logistic regression analysis demonstrated that female sex, chronic kidney disease, and eGFR were independent risk factors for CI-AKI, but contrast volume was not. The administration of high (300-500 mL) and very high (>500 mL) dose of iodixanol is associated with low rates of CI-AKI.
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http://dx.doi.org/10.1177/0003319720953044DOI Listing
February 2021

Three-dimensional facial-image analysis to predict heterogeneity of the human ageing rate and the impact of lifestyle.

Nat Metab 2020 09 7;2(9):946-957. Epub 2020 Sep 7.

CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Not all individuals age at the same rate. Methods such as the 'methylation clock' are invasive, rely on expensive assays of tissue samples and infer the ageing rate by training on chronological age, which is used as a reference for prediction errors. Here, we develop models based on convoluted neural networks through training on non-invasive three-dimensional (3D) facial images of approximately 5,000 Han Chinese individuals that achieve an average difference between chronological or perceived age and predicted age of ±2.8 and 2.9 yr, respectively. We further profile blood transcriptomes from 280 individuals and infer the molecular regulators mediating the impact of lifestyle on the facial-ageing rate through a causal-inference model. These relationships have been deposited and visualized in the Human Blood Gene Expression-3D Facial Image (HuB-Fi) database. Overall, we find that humans age at different rates both in the blood and in the face, but do so coherently and with heterogeneity peaking at middle age. Our study provides an example of how artificial intelligence can be leveraged to determine the perceived age of humans as a marker of biological age, while no longer relying on prediction errors of chronological age, and to estimate the heterogeneity of ageing rates within a population.
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http://dx.doi.org/10.1038/s42255-020-00270-xDOI Listing
September 2020

Bimetallic nanoparticles against multi-drug resistant bacteria.

Chem Commun (Camb) 2020 Sep 18;56(74):10918-10921. Epub 2020 Aug 18.

School of Life Science and Technology, Harbin Institute of Technology, 2 Yikuang Road, Nangang District, Harbin 150001, P. R. China.

We discovered two antibacterial bimetallic nanoparticles (AuRh and AuRu NPs), that possess antibacterial activities against multi-drug resistant (MDR) Gram-negative bacteria and can cure wound infections. None of the nanoparticles comprising just one of these metals elements shows any antibiotic activities.
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http://dx.doi.org/10.1039/d0cc03481aDOI Listing
September 2020

Anti-migration and anti-invasion effects of 2-hydroxy-6-tridecylbenzoic acid is associated with the enhancement of CYP1B1 expression through activating the AMPK signaling pathway in triple-negative breast cancer cells.

Nat Prod Res 2020 Aug 11:1-5. Epub 2020 Aug 11.

College of Food Science and Technology, Shenyang Agricultural University, Shenyang, China.

2-hydroxy-6-tridecylbenzoic acid is alkylsalicylic acid monomer compound, abundantly existed in the ginkgo biloba extracts, however, the underlying mechanism of its anti-migration and anti-invasion effects in triple-negative breast cancer (TNBC) is not clear. Here, 2-hydroxy-6 -tridecylbenzoic acid inhibited MDA-MB-231 and 4 T-1 cells growth without toxicity to MCF-10A normal breast cells. Meanwhile, 2-hydroxy-6-tridecylbenzoic acid inhibited cells migration and invasion as well as EMT with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, Vimentin, Snail, MMP-2 and MMP-9 expression. The inhibition was further demonstrated by the enhancement of cytochrome P450 (CYP) 1B1 expression through the activation of AMP activated protein kinase (AMPK) in MDA-MB-231 and 4 T-1 cells. Silencing of CYP1B1 and AMPK with siRNA blocked the inhibitory effects of migration and invasion, and reversed the EMT related genes. These findings may provide a novel mechanism of the 2-hydroxy-6-tridecylbenzoic acid as a molecular-targeted therapeutic drug for TNBC patients.
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http://dx.doi.org/10.1080/14786419.2020.1803310DOI Listing
August 2020

Clinical Characteristics and Eosinophils in Young SARS-CoV-2-Positive Chinese Travelers Returning to Shanghai.

Front Public Health 2020 10;8:368. Epub 2020 Jul 10.

Department of Image, Shanghai Pudong New Area People's Hospital Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, China.

The COVID-19 outbreak, which was first reported in Wuhan, China, in December 2019, began to spread throughout the world, and now involves over 200 countries. A total of 37 overseas young and middle-aged people, who tested as SARS-CoV-2 positive upon their return to Shanghai, were enrolled for an analysis of their clinical symptoms, blood routine indexes, and lung CT images. The clinical symptoms were characterized by fever (51.4%), dry cough (13.5%), expectoration (27.0%), hypodynamia (21.6%), pharyngalia (10.8%), pharynoxerosis (8.1%), rhinobyon (13.5%), rhinorrhea (8.1%), muscular soreness (16.2%), and diarrhea (2.7%). In 16.2% of cases, no symptoms were reported. Fever was the most common symptom (51.40%). The pneumonic changes referred to the latticed ground glass imaging and similar white lung imaging accompanied by consolidated shadows. The rate of pneumonia was high (81.10%). We found that the exclusive percent of eosinophils was abnormally low. By analyzing the correlation of eosinophils, fever, and pneumonia, we found that the percentage of eosinophils was low in the COVID-19 patients afflicted with fever or pneumonia ( < 0.01). Additionally, pneumonia and fever were negatively correlated with the percentage of eosinophils and eosinophils/neutrophils ratio ( < 0.01, respectively), but not associated with pneumonia severity ( > 0.05). Fever was not correlated with pneumonia ( > 0.05). A low percentage of eosinophils may be considered as a biomarker of pneumonia of COVID-19, but not as a biomarker of pneumonia severity.
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http://dx.doi.org/10.3389/fpubh.2020.00368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365885PMC
July 2020

Artificial intelligence to improve back pain outcomes and lessons learnt from clinical classification approaches: three systematic reviews.

NPJ Digit Med 2020 9;3:93. Epub 2020 Jul 9.

Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC Australia.

Artificial intelligence and machine learning (AI/ML) could enhance the ability to detect patterns of clinical characteristics in low-back pain (LBP) and guide treatment. We conducted three systematic reviews to address the following aims: (a) review the status of AI/ML research in LBP, (b) compare its status to that of two established LBP classification systems (STarT Back, McKenzie). AI/ML in LBP is in its infancy: 45 of 48 studies assessed sample sizes <1000 people, 19 of 48 studies used ≤5 parameters in models, 13 of 48 studies applied multiple models and attained high accuracy, 25 of 48 studies assessed the binary classification of LBP versus no-LBP only. Beyond the 48 studies using AI/ML for LBP classification, no studies examined use of AI/ML in prognosis prediction of specific sub-groups, and AI/ML techniques are yet to be implemented in guiding LBP treatment. In contrast, the STarT Back tool has been assessed for internal consistency, test-retest reliability, validity, pain and disability prognosis, and influence on pain and disability treatment outcomes. McKenzie has been assessed for inter- and intra-tester reliability, prognosis, and impact on pain and disability outcomes relative to other treatments. For AI/ML methods to contribute to the refinement of LBP (sub-)classification and guide treatment allocation, large data sets containing known and exploratory clinical features should be examined. There is also a need to establish reliability, validity, and prognostic capacity of AI/ML techniques in LBP as well as its ability to inform treatment allocation for improved patient outcomes and/or reduced healthcare costs.
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http://dx.doi.org/10.1038/s41746-020-0303-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347608PMC
July 2020

The significance of multidisciplinary classifications based on transbronchial pathology in possible idiopathic interstitial pneumonias.

Medicine (Baltimore) 2020 Jul;99(28):e20930

Department of Respiratory.

Surgical lung biopsy is regarded as the golden standard for the diagnosis of idiopathic interstitial pneumonias (IIPs). Here, we attempted to show the diagnostic accuracy of multidisciplinary classifications based on transbronchial pathology including transbronchial lung cryobiopsy (TBLC) , bronchoalveolar lavage fluid (BALF) and endobronchial ultrasound-guided transbronchial needle aspiration biopsy (EBUS-TBNA).Patients with suspected interstitial lung diseases admitted from June 1, 2016 to December 31, 2018 were involved. Patients with known causes of interstitial lung diseases and typical idiopathic pulmonary fibrosis diagnosed through clinical, radiological information were excluded. Patients with atypical idiopathic pulmonary fibrosis and possible IIPs accepted transbronchial pathological evaluation. Initial multidisciplinary diagnosis (MDD) classifications were made depending on clinical, radiological and transbronchial pathological information by a multidisciplinary team (MDT). The final MDD classifications were confirmed by subsequent therapeutic effects. All patients were followed up for at least 6 months.A total of 70 patients were finally involved. The samples of lung parenchyma extracted through TBLC were enough for confirmation of pathological diagnoses in 68.6% (48/70) cases. Samples of 6 cases were extracted by EBUS-TBNA. Bacteriological diagnoses were positive in 1 case by BALF. Pathological diagnoses of 77.1% (54/70) cases were achieved through TBLC, EBUS-TBNA and BALF. During the follow up study, the pulmonary lesions of 60% patients were improved, 11.43% were relapsed when glucocorticoid was reduced to small dose or withdrawal, 14.29% were leveled off and 8.57% were progressed. The diagnoses of 4 patients with progressed clinical feature were revised. As a result, 94.3% initial MDD classifications based on transbronchial pathology were consistent with the final MDD, and the difference of diagnostic yield wasn't significant between initial and final MDD (Z = -1.414, P = .157).Classifications of IIPs based on transbronchial pathology were useful and quite agreed with final MDD.
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http://dx.doi.org/10.1097/MD.0000000000020930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360311PMC
July 2020

The impact of telemental health use on healthcare costs among commercially insured adults with mental health conditions.

Curr Med Res Opin 2020 Sep 7;36(9):1541-1548. Epub 2020 Aug 7.

Department of Pharmaceutical Systems and Policy, School of Pharmacy, West Virginia University, Morgantown, WV, USA.

Objective: To determine the impact of telemental health (TMH) use on total healthcare costs and mental health (MH)-related costs paid by a third party among adults with mental health conditions (MHC).

Method: This study employed a pre-post design with a non-equivalent control group. The cohort comprised adults with MHCs identified using diagnosis codes from de-identified claims data of the Optum Clinformatics DataMart (2010 January 01 to 2017 June 30). We identified mental health (MH) service users and TMH users ( = 348) based on procedure codes. Non-users ( = 238,595) were defined as those who only used in-person MH services. A Difference-in-Differences (DID) analysis was performed within a multivariable two-part model (TPM) framework to examine the impact of TMH use on adjusted standardized costs (2018 US $) of all healthcare services and MH services. Patient-level and state-level factors were adjusted in TPM.

Results: TMH use was associated with significantly higher MH-related costs [Marginal effect = $461.3, 95% confidence interval: $142.4-$780.2] and an excess of $370 increase in MH-related costs at follow-up as compared to baseline. However, TMH use was not associated with an increase in total third-party healthcare costs nor with changes in total costs from baseline to follow-up.

Conclusions: Despite having a higher likelihood of MH services use and MH-related costs, TMH users did not have higher total costs as compared to adults using only in-person MH services. Our findings suggest that TMH can increase access to MH care without increasing total healthcare costs among adults with MHC. Future studies exploring whether TMH use can lead to cost-savings over a longer period are warranted.
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http://dx.doi.org/10.1080/03007995.2020.1790345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535072PMC
September 2020

miR-423 Promotes Breast Cancer Invasion by Activating NF-κB Signaling.

Onco Targets Ther 2020 12;13:5467-5478. Epub 2020 Jun 12.

GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, People's Republic of China.

Objective: Breast cancer has become the most common malignancy among women worldwide; therefore, novel diagnostic and prognostic markers and therapeutic targets are urgently required. NF-κB signaling plays a pivotal role in enhancing breast cancer malignant phenotypes, especially cancer invasion and metastasis, which is the main cause of death in cancer patients. TNIP2, an important inhibitor of the NF-κB pathway, is known to involve a negative feedback loop of the NF-κB signaling cascade and to regulate tumor aggressiveness in various cancer types. However, the mRNA level of TNIP2 is barely altered in breast cancer; thus, the mechanism that regulates TNIP2 in breast cancer still needs to be elucidated.

Methods: We analyzed the expression and prognosis of miR-423 in a TCGA BRCA miRNA cohort and in clinical specimens. We detected the invasive capacity through a Matrigel-coated Transwell penetration assay, a three-dimensional (3D) spheroid invasion assay and a wound healing assay. Then, we applied luciferase assays, real-time PCR assays and Western blotting to further study the mechanism.

Results: In this study, analysis of the TCGA BRCA miRNA cohort and clinical specimens demonstrated that miR-423 was upregulated in human breast cancers and was positively correlated with clinical stage, poor overall survival and metastasis classification. Moreover, the invasiveness of breast cancer cells was enhanced by ectopic expression of miR-423 and inhibited by miR-423 downregulation. Mechanistically, upregulation of miR-423 led to activation of the NF-κB signaling pathway and elevated expression of snail and twist, while repression of miR-423 inhibited this pathway. Furthermore, the results indicated that TNIP2 is a target gene of miR-423, and suppression of TNIP2 resulted in increased invasiveness in miR-423-silenced cells.

Conclusion: Our results suggest that miR-423 is a crucial factor that enhances breast cancer cell invasion through the NF-κB signaling pathway and shed light on miR-423 as a promising prognostic and therapeutic marker for metastatic breast cancer.
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http://dx.doi.org/10.2147/OTT.S236514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297514PMC
June 2020