Publications by authors named "Ping He"

1,138 Publications

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Associations between childhood adversities and late-life cognitive function: Potential mechanisms.

Authors:
Ruoxi Ding Ping He

Soc Sci Med 2021 Oct 9;291:114478. Epub 2021 Oct 9.

China Center for Health Development Studies, Peking University, Beijing, 100191, China. Electronic address:

Rationale: Childhood adversity, which is related to negative cognitive consequences, is highly prevalent across the world. Nonetheless, there is still a scarcity of research on late-life cognitive function that accounted for multiple aspects of adverse events as well as the potential mediating mechanism of social context and individual's wellbeing in adulthood.

Objective: This study aimed to investigate the relationship between childhood adversities and late-life cognitive function among the middle-aged and older Chinese population and to determine the mediating role of education attainment, marital status, financial status, and self-rated health in adulthood.

Methods: We used three waves of data from China Health and Retirement Longitudinal Study from 2011 to 2015, which consisted of 23 807 participants aged 45 years and older. Generalized Estimating Equation and Structural Equation Model were applied to examine the association between childhood adversities and cognitive function (mental intactness and episodic memory) and the corresponding potential mechanisms.

Results: Overall, 77.25%, 64.55%, 38.38%, and 15.03% of respondents experienced socioeconomic disadvantage, parental involved trauma, maladaptive parental trauma, and other trauma in childhood, respectively. Multivariate analyses suggest that all four types of childhood adversities were associated with a lower score of mental intactness and the first three were associated with episodic memory. A large proportion of the associations between childhood adversity and cognitive function was mainly mediated by education attainment, self-rated health and marital status in adulthood.

Conclusion: There are negative linkages between childhood adversities and cognitive function in the middle-aged and older Chinese population. Such associations were primarily functioning indirectly through adult social context and health conditions.
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http://dx.doi.org/10.1016/j.socscimed.2021.114478DOI Listing
October 2021

The Association between the Community SARS Exposure and Allostatic Load among Chinese Older Adults.

Authors:
Xin Ye Ping He

J Am Geriatr Soc 2021 Oct 11. Epub 2021 Oct 11.

China Center for Health Development Studies, Peking University, Beijing, China.

Objectives: Previous studies have found that Severe Acute Respiratory Syndrome (SARS) was associated with the physical and psychological stress of those infected. However, research is sparse regarding the long-term health consequence of community SARS exposure for older adults.

Methods: Using data from the 2011 and 2015 China Health and Retirement Longitudinal Study (CHARLS), we estimated multilevel regression models of allostatic load in the years after the SARS epidemic among 7735 respondents. Interaction terms between SARS epidemic exposure and social participation or community environment were included to examine potential effects.

Results: We found that community SARS exposure was associated with greater allostatic load for those who had no social participation. Among those who were in worse community environment, community SARS exposure was strongly related to elevated load in the cardiovascular system. However, for those had social participation and lived in better community environment, community SARS exposure manifested no association with allostatic load years later. Active social participation and better community environment could offset the negative association between SARS exposure and allostatic load.

Conclusions: Taken together, these findings helped determine the positive direction of future social efforts and policy decisions to guide the global recovery from the devastating COVID-19 pandemic. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jgs.17516DOI Listing
October 2021

Dihydroartemisinin-Loaded Chitosan Nanoparticles Inhibit the Rifampicin-Resistant by Disrupting the Cell Wall.

Front Microbiol 2021 22;12:735166. Epub 2021 Sep 22.

Department of Clinical Laboratory, Sichuan Mianyang 404 Hospital, Mianyang, China.

Tuberculosis (TB) caused by (MTB) is a deadly infection, and increasing resistance worsens an already bad scenario. In this work, a new nanomedicine antibacterial agent, based on dihydroartemisinin (DHA) and chitosan (CS), has been successfully developed to overcome MTB's drug-resistant. To enhance DHA's solubility, we have prepared nanoparticles of DHA loaded CS by an ionic crosslinking method with sodium tripolyphosphate (STPP) as the crosslinking agent. The DHA-CS nanoparticles (DHA-CS NPs) have been fully characterized by scanning electron microscopy, Fourier transforms infrared spectroscopy, dynamic light scattering, and ultraviolet spectrophotometry. DHA-CS NPs show an excellent antibacterial effect on the rifampicin (RFP)-resistant strain (ATCC 35838) and, at a concentration of 8.0 μg/ml, the antibacterial impact reaches up to 61.0 ± 2.13% ( = 3). The results of Gram staining, acid-fast staining, auramine "O" staining and electron microscopy show that the cell wall of RFP-resistant strains is destroyed by DHA-CS NPs ( = 3), and it is further verified by gas chromatography-mass spectrometry. Since all the metabolites identified in DHA-CS NPs treated RFP-resistant strains indicate an increase in fatty acid synthesis and cell wall repair, it can be concluded that DHA-CS NPs act by disrupting the cell wall. In addition, the resistance of 12 strains is effectively reduced by 8.0 μg/ml DHA-CS NPs combined with RFP, with an effective rate of 66.0%. The obtained results indicate that DHA-CS NPs combined with RFP may have potential use for TB treatment.
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http://dx.doi.org/10.3389/fmicb.2021.735166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500176PMC
September 2021

Morphological diversity of single neurons in molecularly defined cell types.

Nature 2021 10 6;598(7879):174-181. Epub 2021 Oct 6.

School of Computer Engineering and Science, Shanghai University, Shanghai, China.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.
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http://dx.doi.org/10.1038/s41586-021-03941-1DOI Listing
October 2021

Whole-genome sequencing for surveillance of tuberculosis drug resistance and determination of resistance level in China.

Clin Microbiol Infect 2021 Sep 30. Epub 2021 Sep 30.

Chinese Centre for Disease Control and Prevention, Beijing, China. Electronic address:

Objectives: Phenotypic drug susceptibility testing for prediction of tuberculosis (TB) drug resistance is slow and unreliable, limiting individualized therapy and monitoring of national TB data. Our study evaluated whole-genome sequencing (WGS) for its predictive accuracy, use in TB drug-resistance surveillance and ability to quantify the effects of resistance-associated mutations on MICs of anti-TB drugs.

Methods: We used WGS to measure the susceptibility of 4880 isolates to ten anti-TB drugs; for pyrazinamide, we used BACTEC MGIT 960. We determined the accuracy of WGS by comparing the prevalence of drug resistance, measured by WGS, with the true prevalence, determined by phenotypic susceptibility testing. We used the Student-Newman-Keuls test to confirm MIC differences of mutations.

Results: Resistance to isoniazid, rifampin and ethambutol was highly accurately predicted with at least 92.92% (95% confidence interval [CI], 88.19-97.65) sensitivity, resistance to pyrazinamide with 50.52% (95% CI, 40.57-60.47) sensitivity, and resistance to six second-line drugs with 85.05% (95% CI, 80.27-89.83) to 96.01% (95% CI, 93.89-98.13) sensitivity. The rpoB S450L, katG S315T and gyrA D94G mutations always confer high-level resistance, while rpoB L430P, rpoB L452P, fabG1 C-15T and embB G406S often confer low-level resistance or sub-epidemiological cutoff (ECOFF) MIC elevation.

Conclusion: WGS can predict phenotypic susceptibility with high accuracy and could be a valuable tool for drug-resistance surveillance and allow the detection of drug-resistance level; It can be an important approach in TB drug-resistance surveillance and for determining therapeutic schemes.
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http://dx.doi.org/10.1016/j.cmi.2021.09.014DOI Listing
September 2021

Noncanonical mono(ADP-ribosyl)ation of zinc finger SZF proteins counteracts ubiquitination for protein homeostasis in plant immunity.

Mol Cell 2021 Sep 21. Epub 2021 Sep 21.

Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA. Electronic address:

Protein ADP-ribosylation is a reversible post-translational modification that transfers ADP-ribose from NAD onto acceptor proteins. Poly(ADP-ribosyl)ation (PARylation), catalyzed by poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolases (PARGs), which remove the modification, regulates diverse cellular processes. However, the chemistry and physiological functions of mono(ADP-ribosyl)ation (MARylation) remain elusive. Here, we report that Arabidopsis zinc finger proteins SZF1 and SZF2, key regulators of immune gene expression, are MARylated by the noncanonical ADP-ribosyltransferase SRO2. Immune elicitation promotes MARylation of SZF1/SZF2 via dissociation from PARG1, which has an unconventional activity in hydrolyzing both poly(ADP-ribose) and mono(ADP-ribose) from acceptor proteins. MARylation antagonizes polyubiquitination of SZF1 mediated by the SH3 domain-containing proteins SH3P1/SH3P2, thereby stabilizing SZF1 proteins. Our study uncovers a noncanonical ADP-ribosyltransferase mediating MARylation of immune regulators and underpins the molecular mechanism of maintaining protein homeostasis by the counter-regulation of ADP-ribosylation and polyubiquitination to ensure proper immune responses.
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http://dx.doi.org/10.1016/j.molcel.2021.09.006DOI Listing
September 2021

An ion-paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection.

Bioeng Transl Med 2021 Sep 22;6(3):e10238. Epub 2021 Jun 22.

The Center for Nanomedicine, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USA.

There are numerous barriers to achieving effective intraocular drug administration, including the mucus layer protecting the ocular surface. For this reason, antibiotic eye drops must be used multiple times per day to prevent and treat ocular infections. Frequent eye drop use is inconvenient for patients, and lack of adherence to prescribed dosing regimens limits treatment efficacy and contributes to antibiotic resistance. Here, we describe an ion-pairing approach used to create an insoluble moxifloxacin-pamoate (MOX-PAM) complex for formulation into mucus-penetrating nanosuspension eye drops (MOX-PAM NS). The MOX-PAM NS provided a significant increase in ocular drug absorption, as measured by the area under the curve in cornea tissue and aqueous humor, compared to Vigamox in healthy rats. Prophylactic and treatment efficacy were evaluated in a rat model of ocular infection. A single drop of MOX-PAM NS was more effective than Vigamox, and completely prevented infection. Once a day dosing with MOX-PAM NS was similar, if not more effective, than three times a day dosing with Vigamox for treating infection. The MOX-PAM NS provided increased intraocular antibiotic absorption and improved prevention and treatment of ocular keratitis, and the formulation approach is highly translational and clinically relevant.
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http://dx.doi.org/10.1002/btm2.10238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459599PMC
September 2021

A Reverse Transcription Recombinase-Aided Amplification Method for Rapid and Point-of-Care Detection of SARS-CoV-2, including Variants.

Viruses 2021 09 19;13(9). Epub 2021 Sep 19.

CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.

The worldwide pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its emergence of variants needs rapid and point-of-care testing methods for a broad diagnosis. The regular RT-qPCR is time-consuming and limited in central laboratories, so a broad and large-scale screening requirement calls for rapid and in situ methods. In this regard, a reverse transcription recombinase-aided amplification (RT-RAA) is proposed here for the rapid and point-of-care detection of SARS-CoV-2. A set of highly conserved primers and probes targeting more than 98% of SARS-CoV-2 strains, including currently circulating variants (four variants of concerns (VOCs) and three variants of interest (VOIs)), was used in this study. With the preferred primers, the RT-RAA assay showed a 100% specificity to SARS-CoV-2 from eight other respiratory RNA viruses. Moreover, the assay here is of a high sensitivity and 0.48 copies/μL can be detected within 25 min at a constant temperature (42 °C), which can be realized on portable equipment. Furthermore, the RT-RAA assay demonstrated its high agreement for the detection of SARS-CoV-2 in clinical specimens compared with RT-qPCR. The rapid, simple and point-of-care RT-RAA method is expected to be an appealing detection tool to detect SARS-CoV-2, including variants, in clinical diagnostic applications.
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http://dx.doi.org/10.3390/v13091875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472806PMC
September 2021

Emergy-based evaluation of world coastal ecosystem services.

Water Res 2021 Oct 11;204:117656. Epub 2021 Sep 11.

University of Florence, Department of Economics and Management, University of Firenze, Via Delle Pandette 9, Firenze, Italy.

The current lack of research on the evaluation of marine ecosystem services makes the value of marine protection, development and restoration underestimated during the decision-making process. Based on the non-monetary ecosystem service evaluation framework, a marine ecosystem service classification and accounting method has been established in this study, and the world's coastal ecosystem services have been measured as an example. The results show that (1) the world's coastal ecosystem service value is about 4.13E+23 sej/yr, of which Asia and North America contribute about 55% of the total service value; (2) the top ten countries in terms of the world's coastal ecosystem service values are Canada, Indonesia, Australia, the United States, Brazil, the Russian Federation, Norway, the Philippines, Mexico, and China, which contribute about 60% of the total service value; (3) estuaries have the highest ecosystem service values, followed by mangroves, seagrass beds, tidal flats, salt marshes, and warm water coral reefs; (4) developed countries can make better use of their coastal resources and pay more attention to the marine protection while the opposite is true in developing countries, which means that developed countries still occupy an advantageous position in the process of marine protection, development and utilization. This study assesses the coastal ecosystem service values in various coastal countries from the perspective of ecosystem contributors, emphasizes the importance of protecting them in marine management, and provides a certain reference basis and theoretical support for decision-makers in formulating marine-related protection and development strategies.
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http://dx.doi.org/10.1016/j.watres.2021.117656DOI Listing
October 2021

The Arabidopsis MIK2 receptor elicits immunity by sensing a conserved signature from phytocytokines and microbes.

Nat Commun 2021 09 17;12(1):5494. Epub 2021 Sep 17.

Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.

Sessile plants encode a large number of small peptides and cell surface-resident receptor kinases, most of which have unknown functions. Here, we report that the Arabidopsis receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) recognizes the conserved signature motif of SERINE-RICH ENDOGENOUS PEPTIDEs (SCOOPs) from Brassicaceae plants as well as proteins present in fungal Fusarium spp. and bacterial Comamonadaceae, and elicits various immune responses. SCOOP signature peptides trigger immune responses and altered root development in a MIK2-dependent manner with a sub-nanomolar sensitivity. SCOOP12 directly binds to the extracellular leucine-rich repeat domain of MIK2 in vivo and in vitro, indicating that MIK2 is the receptor of SCOOP peptides. Perception of SCOOP peptides induces the association of MIK2 and the coreceptors SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3 (SERK3) and SERK4 and relays the signaling through the cytosolic receptor-like kinases BOTRYTIS-INDUCED KINASE 1 (BIK1) and AVRPPHB SUSCEPTIBLE1 (PBS1)-LIKE 1 (PBL1). Our study identifies a plant receptor that bears a dual role in sensing the conserved peptide motif from phytocytokines and microbial proteins via a convergent signaling relay to ensure a robust immune response.
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http://dx.doi.org/10.1038/s41467-021-25580-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448819PMC
September 2021

Systematic review and meta-analysis on efficacy of traditional Chinese medicine for atrial fibrillation through cluster analysis.

Ann Palliat Med 2021 Aug;10(8):8982-8990

Operational Department, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.

Background: Traditional Chinese medicine (TCM) has shown excellent therapeutic effects in the treatment of heart diseases. This meta-analysis was to evaluate the therapeutic effects of TCM on patients with atrial fibrillation (AF).

Methods: Four databases were searched from their establishment to 1 April 2021 for randomized controlled trials (RCTs) on the treatment of AF using TCM. The Cochrane Handbook 5.0.2 was used to perform to bias risk assessment, and RevMan 5.3 was used for meta-analysis.

Results: A total of 7 references were included. It was found that compared with conventional Western medicine, the effective rate of TCM or the combined therapy of TCM and Western medicine was higher [mean difference (MD) =1.85; 95% confidence interval (CI): 1.28 to 2.68; Z=3.26; P=0.001]; the success rate of conversion was increased (MD =1.58; 95% CI: 1.02 to 2.44; Z=2.06; P=0.04), the conversion time was shortened (MD =-224.82; 95% CI: -262.56 to -187.08; Z=11.68; P<0.00001), the incidence of adverse reactions was reduced (MD =0.62; 95% CI: 0.40 to 0.97; Z=2.11; P=0.03).

Discussion: The use of TCM to treat AF can improve clinical treatment efficiency, increase the success rate of conversion, and shorten the conversion time. Compared with conventional Western medicine, the combined therapy demonstrated better therapeutic effects.
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http://dx.doi.org/10.21037/apm-21-1785DOI Listing
August 2021

Nitrogen balance acts an indicator for estimating thresholds of nitrogen input in rice paddies of China.

Environ Pollut 2021 Dec 2;290:118091. Epub 2021 Sep 2.

Ministry of Agriculture and Rural Affairs Key Laboratory of Plant Nutrition and Fertilizer, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Decision-making related to nitrogen (N) fertilization is a crucial step in agronomic practices because of its direct interactions with agronomic productivity and environmental risk. Here, we hypothesized that soil apparent N balance could be used as an indicator to determine the thresholds of N input through analyzing the responses of the yield and N loss to N balance. Based on the observations from 951 field experiments conducted in rice (Oryza sativa L.) cropping systems of China, we established the relationships between N balance and ammonia (NH) volatilization, yield increase ratio, and N application rate, respectively. Dramatical increase of NH volatilizations and stagnant increase of the rice yields were observed when the N surplus exceeded certain levels. Using a piecewise regression method, the seasonal upper limits of N surplus were determined as 44.3 and 90.9 kg N ha under straw-return and straw-removal scenarios, respectively, derived from the responses of NH volatilization, and were determined as 53.0-74.9 and 97.9-112.0 kg N ha under straw-return and straw-removal scenarios, respectively, derived from the maximum-yield consideration. Based on the upper limits of N surplus, the thresholds of N application rate suggested to be applied in single, middle-MLYR, middle-SW, early, and late rice types ranged 179.0-214.9 kg N ha in order to restrict the NH volatilization, and ranged 193.3-249.8 kg N ha in order to achieve the maximum yields. If rice straw was returned to fields, on average, the thresholds of N application rate could be theoretically decreased by 17.5 kg N ha. This study provides a robust reference for restricting the N surplus and the synthetic fertilizer N input in rice fields, which will guide yield goals and environmental protection.
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http://dx.doi.org/10.1016/j.envpol.2021.118091DOI Listing
December 2021

Evaluation of Multidrug Resistant Loop-mediated Isothermal Amplification Assay for Detecting the Drug Resistance of .

Biomed Environ Sci 2021 Aug;34(8):616-622

National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

Objective: To evaluate multidrug resistant loop-mediated isothermal amplification (MDR-LAMP) assay for the early diagnosis of multidrug-resistant tuberculosis and to compare the mutation patterns associated with the , , and genes at the Chinese Center for Disease Control and Prevention.

Methods: MDR-LAMP assay was evaluated using 100 ( ) isolates obtained from the National Reference Laboratory for Tuberculosis in China. Phenotypic resistance to isoniazid and rifampicin and whole-genome sequencing served as reference standards.

Results: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDR-LAMP were 85.5%, 93.6%, 96.7%, and 74.4% for the detection of resistance to isoniazid and rifampicin, respectively, and 80.5%, 92.3%, 98.6%, and 41.4% for the detection of cultured from smear-positive sputum samples, respectively. When DNA sequencing was used as the reference standard, the sensitivity, specificity, PPV, and NPV of MDR-LAMP were 93.1%, 92.3%, 97.2%, and 82.8% for the detection of and gene mutations, respectively, and 89.1%, 88.9%, 93.4%, and 81.1% for the detection of gene mutation, respectively.

Conclusion: MDR-LAMP is a rapid and accessible assay for the laboratory identification of rifampicin and isoniazid resistance of isolates.
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http://dx.doi.org/10.3967/bes2021.085DOI Listing
August 2021

Impact of COVID-19 pandemic on emergency psychiatry-Millcreek community hospital, Erie, PA.

Compr Psychiatry 2021 10 12;110:152255. Epub 2021 Jun 12.

Department of Psychiatry, Millcreek Community Hospital, Lake Erie College of Osteopathic Medicine, Erie, PA, USA. Electronic address:

Objective: Evidence suggested that traumatic events, including pandemics, can be associated with psychiatric symptoms like increased anxiety and depression. However, there were many unknowns concerning the emergent global coronavirus-19 (COVID-19), including its impact on psychiatric health within the United States. Our study aimed to track trends of mental health problems in individuals who presented with psychiatric complaints in an emergent setting.

Methods: A total of 1776 patients and 1610 patients presented to Emergency Department (ED) with psychiatric complaints between January 1 - July 9 of the years of 2019 and 2020, respectively, in Millcreek Community Hospital (MCH) Erie, PA. This study was an electronic medical record review (EMR), therefore the data were collected exclusively from EMR over the two-year span. ED prevalence was calculated as the number of total psychiatric MCH ED cases divided by the total number of all MCH ED patients, and prevalence ratio (PR) between 2019 and 2020 was used to reflect change of overall ED psychiatric prevalence.

Results: Clinical notes revealed increased ED psychiatric chief complaint prevalence, as indicated by a PR greater than one, in multiple categories in comparison to before the COVID-19 outbreak. Concerning primary psychiatric disorders, there was increased ED prevalence in chief complaint of total mood disorders (PR = 1.21) with major depressive disorder (PR = 1.23) and bipolar disorder (PR = 1.47), neurodevelopment disorders (PR = 1.25) with attention deficit hyperactivity disorder (ADHD) (PR = 1.19) and intellectual disability (PR = 1.52), trauma- and stressor-related disorders (PR = 1.56) with post-traumatic stress disorder (PTSD) (PR = 1.39) and adjustment disorder (PR = 1.73), substance abuse and addiction disorders (PR = 1.29), and personality disorders (PR = 1.56).

Conclusions: The pandemic outbreak dramatically impacted mental health in an ER setting. Further research on mental health disparities in conjunction with the COVID-19 pandemic is critical to help predict and address risk for chronic symptoms and sequela to help anticipate and improve psychiatric patient care and well-being during potential future pandemics.
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http://dx.doi.org/10.1016/j.comppsych.2021.152255DOI Listing
October 2021

Effects of hypoxia on DNA hydroxymethylase Tet methylcytosine dioxygenase 2 in a KG-1 human acute myeloid leukemia cell line and its mechanism.

Oncol Lett 2021 Oct 1;22(4):692. Epub 2021 Aug 1.

Department of Hematology, The Affiliated Changsha Hospital, Hunan Normal University, Changsha, Hunan 410006, P.R. China.

Hypoxia is involved in the epigenetic modification of leukemia. As an important DNA hydroxymethylase and a tumor suppressor gene, the expression regulating mechanism of Tet methylcytosine dioxygenase 2 (TET2) remains unclear. The aim of the present study was to explore whether hypoxia and hypoxia-inducible factor 1α (HIF-1α) regulate TET2 gene expression and its demethylation function in acute myeloid leukemia (AML). The human AML cell line KG-1 was used in the present study. The results demonstrated that hypoxia could increase proliferation, enhance metabolism and inhibit apoptosis in KG-1 cells, as detected by the cell counting kit-8 assay, lactate dehydrogenase assay and Annexin V-FITC/propidium iodide staining, respectively. Hypoxia reduced the genome methylation status in KG-1 cells detected using 5-methylcytosine and 5-hydroxymethylcytosine detection kits. In addition, HIF-1α overexpression increased TET2 expression, 5-hmC level and cyclin-dependent kinase inhibitor 2B [p15(INK4B)] gene demethylation compared with the HIF-1α non-overexpression group in KG-1 cells detected by reverse transcription-quantitative PCR, western blotting, 5-hydroxymethylcytosine detection kits and methylation-specific PCR, respectively. The inhibition of HIF-1α by inhibitor YC-1 reduced demethylation in KG-1 cells by decreasing TET2 expression. It was also revealed that HIF-1α could enhance TET2 transcriptional activity by binding to the hypoxia response element of the TET2 gene promoter region using chromatin immunoprecipitation and luciferase reporter gene assays. TET2 may be a potential target gene regulated by HIF-1α. Hypoxia was demonstrated to regulate the expression of TET2 by HIF-1α, which in turn affected the methylation and expression of downstream target genes and served a role in the occurrence and progression of leukemia. In the present study, the association between hypoxia metabolism and epigenetic regulation in AML was investigated and the findings provided a new idea and experimental basis for the diagnosis and treatment of hematologic malignancies.
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http://dx.doi.org/10.3892/ol.2021.12953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358611PMC
October 2021

Long Noncoding RNAs in Neurodegenerative Diseases: Pathogenesis and Potential Implications as Clinical Biomarkers.

Front Mol Neurosci 2021 4;14:685143. Epub 2021 Aug 4.

Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), are progressive and ultimately fatal. NDD onset is influenced by several factors including heredity and environmental cues. Long noncoding RNAs (lncRNAs) are a class of noncoding RNA molecules with: (i) lengths greater than 200 nucleotides, (ii) diverse biological functions, and (iii) highly conserved structures. They directly interact with molecules such as proteins and microRNAs and subsequently regulate the expression of their targets at the genetic, transcriptional, and post-transcriptional levels. Emerging studies indicate the important roles of lncRNAs in the progression of neurological diseases including NDDs. Additionally, improvements in detection technologies have enabled quantitative lncRNA detection and application to circulating fluids in clinical settings. Here, we review current research on lncRNAs in animal models and patients with NDDs. We also discuss the potential applicability of circulating lncRNAs as biomarkers in NDD diagnostics and prognostics. In the future, a better understanding of the roles of lncRNAs in NDDs will be essential to exploit these new therapeutic targets and improve noninvasive diagnostic methods for diseases.
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http://dx.doi.org/10.3389/fnmol.2021.685143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371338PMC
August 2021

Coordinated regulation of plant immunity by poly(ADP-ribosyl)ation and K63-linked ubiquitination.

Mol Plant 2021 Aug 18. Epub 2021 Aug 18.

Texas A&M AgriLife Research Center at Dallas, Texas A&M University System, Dallas, TX 75252, USA; Department of Plant Pathology and Microbiology, Texas A&M University, College Station, TX 77843, USA. Electronic address:

Poly(ADP-ribosyl)ation (PARylation) is a posttranslational modification reversibly catalyzed by poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolases (PARGs) and plays a key role in multiple cellular processes. The molecular mechanisms by which PARylation regulates innate immunity remain largely unknown in eukaryotes. Here we show that Arabidopsis UBC13A and UBC13B, the major drivers of lysine 63 (K63)-linked polyubiquitination, directly interact with PARPs/PARGs. Activation of pathogen-associated molecular pattern (PAMP)-triggered immunity promotes these interactions and enhances PARylation of UBC13. Both parp1 parp2 and ubc13a ubc13b mutants are compromised in immune responses with increased accumulation of total pathogenesis-related (PR) proteins but decreased accumulation of secreted PR proteins. Protein disulfide-isomerases (PDIs), essential components of endoplasmic reticulum quality control (ERQC) that ensure proper folding and maturation of proteins destined for secretion, complex with PARPs/PARGs and are PARylated upon PAMP perception. Significantly, PARylation of UBC13 regulates K63-linked ubiquitination of PDIs, which may further promote their disulfide isomerase activities for correct protein folding and subsequent secretion. Taken together, these results indicate that plant immunity is coordinately regulated by PARylation and K63-linked ubiquitination.
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http://dx.doi.org/10.1016/j.molp.2021.08.013DOI Listing
August 2021

Preliminary study of genome-wide association identifies novel susceptibility genes for serum mineral elements in the Chinese Han population.

Biol Trace Elem Res 2021 Aug 21. Epub 2021 Aug 21.

Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, #19, Xiuhua Road, Xiuying District, Haikou #19, Xiuhua Road, Xiuying District, Haikou, Hainan, 570311, People's Republic of China.

Mineral elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe)) play important biological roles in enzymes, hormones, vitamins, and normal metabolism. The deficiency of mineral elements can lead to abnormal physiological functions. And some elements (such as lead (Pb)) are harmful to the body. We aim to identify genetic loci which can influence the serum levels of mineral elements (Cu, Zn, Ca, Mg, Fe, and Pb). Genotyping was performed using Applied Biosystems Axiom™ PMDA in 587 individuals, and 6,423,076 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study (GWAS) analysis. The association between genotype and phenotype was analyzed using mixed linear regression (additive genetic model) adjusting by age and gender combined with identical by descent (IBD) matrix. Genetic loci in BCHE-LOC105374194, DTX2P1-UPK3BP1-PMS2P11, VAT1L, LINC00908-LINC00683, LINC01310-NONE, and rs6747410 in VWA3B were identified to be associated with serum Cu element concentration (p < 5 × 10). ADAMTSL1 rs17229526 (p = 4.96 × 10) was significantly associated with serum Zn element levels. Genetic loci in LRP1B, PIGZ-MELTF, LINC01365-LINC02502, and HAPLN3 were related to serum Ca element levels (p < 5 ×1 0). Three SNPs in ALPK1, ASAP1-ADCY8 and IER3IP1-SKOR2 also achieved a significant association with Mg element levels (p < 5 × 10). TACSTD2-MYSM1, LRP1B, and ASAP1-ADCY8 showed suggestive associations with serum Fe element levels (p < 5 × 10). Moreover, the two most significant SNPs associated with Pb were rs304234 in CADPS-LINC00698 (p = 2.47 × 10) and rs12666460 in LOC101928211-GPR37 (p = 1.81 × 10). In summary, we reported 19 suggestive loci associated with serum mineral elements in the Chinese Han population. These findings provided new insights into the potential mechanisms regulating serum mineral elements levels.
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http://dx.doi.org/10.1007/s12011-021-02854-4DOI Listing
August 2021

Knockout of the Cannabinoid Receptor 2 Gene Promotes Inflammation and Hepatic Stellate Cell Activation by Promoting A20/Nuclear Factor-κB (NF-κB) Expression in Mice with Carbon Tetrachloride-Induced Liver Fibrosis.

Med Sci Monit 2021 Aug 20;27:e931236. Epub 2021 Aug 20.

Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China (mainland).

BACKGROUND This study aimed to investigate the effect of deleting the cannabinoid receptor 2 (CB2) gene on the development of hepatic fibrosis induced by carbon tetrachloride (CCl₄) in mice via regulating inflammation. MATERIAL AND METHODS The DNA was extracted from the tails of mice to identify whether the cannabinoid receptor 2 gene was successfully knocked out. A liver fibrosis model was established by an intraperitoneal injection of CCl₄ into mice. Hepatic damage and hepatic fibrosis were evaluated by detecting serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and staining paraffin sections of liver tissue with hematoxylin-eosin (HE). The secretion and distribution of collagen in liver tissue were observed by Masson staining. Western blot analysis was performed to detect the expression of a-smooth muscle actin (alpha-SMA), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor alpha-induced protein 3 (A20), phosphorylated nuclear factor-kB p65 (p-NF-kappaB p65), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) in liver tissue. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-6 and TNF-alpha mRNA in liver tissue. RESULTS Compared with the control mice, the mice with CB2 knockout that were exposed to CCl₄ exhibited increased liver damage, liver fibrosis, and upregulated alpha-SMA, TGF-ß1, A20, and p-NF-kappaB p65 protein levels. IL-6 and TNF-alpha protein levels and mRNA levels were upregulated. CONCLUSIONS The deletion of the CB2 gene promoted the activation of hepatic stellate cells in mice with liver fibrosis and aggravated liver fibrosis by up-regulating the protein expression of A20 and p-NF-kappaB p65 and inducing inflammatory response, potentially providing new insight into the treatment of liver fibrosis.
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http://dx.doi.org/10.12659/MSM.931236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409143PMC
August 2021

Deep learning-based predictive biomarker of pathological complete response to neoadjuvant chemotherapy from histological images in breast cancer.

J Transl Med 2021 08 16;19(1):348. Epub 2021 Aug 16.

Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.

Background: Pathological complete response (pCR) is considered a surrogate endpoint for favorable survival in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Predictive biomarkers of treatment response are crucial for guiding treatment decisions. With the hypothesis that histological information on tumor biopsy images could predict NAC response in breast cancer, we proposed a novel deep learning (DL)-based biomarker that predicts pCR from images of hematoxylin and eosin (H&E)-stained tissue and evaluated its predictive performance.

Methods: In total, 540 breast cancer patients receiving standard NAC were enrolled. Based on H&E-stained images, DL methods were employed to automatically identify tumor epithelium and predict pCR by scoring the identified tumor epithelium to produce a histopathological biomarker, the pCR-score. The predictive performance of the pCR-score was assessed and compared with that of conventional biomarkers including stromal tumor-infiltrating lymphocytes (sTILs) and subtype.

Results: The pCR-score derived from H&E staining achieved an area under the curve (AUC) of 0.847 in predicting pCR directly, and achieved accuracy, F1 score, and AUC of 0.853, 0.503, and 0.822 processed by the logistic regression method, respectively, higher than either sTILs or subtype; a prediction model of pCR constructed by integrating sTILs, subtype and pCR-score yielded a mean AUC of 0.890, outperforming the baseline sTIL-subtype model by 0.051 (0.839, P  =  0.001).

Conclusion: The DL-based pCR-score from histological images is predictive of pCR better than sTILs and subtype, and holds the great potentials for a more accurate stratification of patients for NAC.
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http://dx.doi.org/10.1186/s12967-021-03020-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365907PMC
August 2021

Detecting drought regulators using stochastic inference in Bayesian networks.

PLoS One 2021 16;16(8):e0255486. Epub 2021 Aug 16.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas, United States of America.

Drought is a natural hazard that affects crops by inducing water stress. Water stress, induced by drought accounts for more loss in crop yield than all the other causes combined. With the increasing frequency and intensity of droughts worldwide, it is essential to develop drought-resistant crops to ensure food security. In this paper, we model multiple drought signaling pathways in Arabidopsis using Bayesian networks to identify potential regulators of drought-responsive reporter genes. Genetically intervening at these regulators can help develop drought-resistant crops. We create the Bayesian network model from the biological literature and determine its parameters from publicly available data. We conduct inference on this model using a stochastic simulation technique known as likelihood weighting to determine the best regulators of drought-responsive reporter genes. Our analysis reveals that activating MYC2 or inhibiting ATAF1 are the best single node intervention strategies to regulate the drought-responsive reporter genes. Additionally, we observe simultaneously activating MYC2 and inhibiting ATAF1 is a better strategy. The Bayesian network model indicated that MYC2 and ATAF1 are possible regulators of the drought response. Validation experiments showed that ATAF1 negatively regulated the drought response. Thus intervening at ATAF1 has the potential to create drought-resistant crops.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255486PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367000PMC
August 2021

Decreased phosphorylation facilitates the degradation of the endogenous protective molecule c-Ski in vascular smooth muscle cells.

Cell Signal 2021 Nov 12;87:110116. Epub 2021 Aug 12.

Department of Cardiac Surgery, The First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing 400038, China. Electronic address:

The dysfunction of vascular smooth muscle cells (VSMCs) is critical for atherosclerosis (AS) progression. Autophagy is indispensable during phenotypic switching and proliferation of VSMCs, contribute to AS development. Cellular Sloan-Kettering Institute (c-Ski), the repressor of TGF-β signaling, is involved in diverse physiological and pathological processes. We previously defined c-Ski also as an endogenous protective molecule against AS via inhibiting abnormal proliferation and autophagy of VSMCs. However, the endogenous level of c-Ski in VSMCs is markedly decreased during the progression of AS, so that the protective effect is drastically weakened. Elucidating the molecular mechanisms is key to the understanding of AS development and treatment. We determined that oxidized low-density lipoprotein (ox-LDL) and platelet-derived growth factor (PDGF) directly induced the degradation of c-Ski protein, closely associated with reducing its phosphorylation. Serine (S383) was identified as the crucial phosphorylation site for stabilizing protein expression and nuclear location of c-Ski, which was responsible for its transcriptional suppression of autophagy-related genes. Decreased S383 phosphorylation facilitated nuclear export and degradation of c-Ski, thereby lessened its inhibitory effect on induction of autophagy genes. These findings provide a novel view of c-Ski modification and function modulation under some vascular injury factors, which point to a new potential therapeutic strategy by targeting c-Ski.
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http://dx.doi.org/10.1016/j.cellsig.2021.110116DOI Listing
November 2021

The protective effect of cannabinoid type II receptor agonist AM1241 on ConA-induced liver injury in mice via mitogen-activated protein kinase signalling pathway.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211035251

Department of Center for Clinical Laboratories, 74628The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China.

Introduction: The endocannabinoid system plays an important role in regulating the immune responses in inflammation. At present, there are no good clinical drugs for many immune liver diseases.

Methods: We explored the protective effect of the cannabinoid type II (CB2) receptor agonist AM1241 on the liver of mice with acute liver injury caused by concanavalin from the perspective of inflammation and immunity. Pathological evaluation in hepatic tissue was examined by haematoxylin and eosin (HE) staining and the levels of biochemical parameters in the serum were measured by automatic biochemical analysis. The content of inflammatory factors was measured by enzyme-linked immunosorbent assay and real-time quantitative reverse transcription polymerase chain reaction (real-time PCR). The liver apoptosis-related proteins were observed by immunohistochemistry. The expression of liver injury-related proteins was analysed by Western blot. Immune cells were isolated from the liver of mice and studied in vitro.

Results: Reduced levels of alanine transaminase and aspartate transaminase were observed in ConA-induced liver injury mice treated with AM1241, together with attenuated liver damage evidenced by H&E staining. Moreover, AM1241 inhibited the protein and gene expression levels of TNF-α, IL-6 and IFN-γ in the livers of mice. The phosphorylation levels of p38, JNK, ERK1/2, P65 and cAMP response element-binding protein (CREB) in the mouse were significantly reduced in AM1241 pretreatment, while the level of p-JNK increased. In addition, the P/T-P65 and P/T-CREB of the AM1241 pretreatment group were significantly reduced. The results of immunohistochemistry measurement are consistent with those of Western blotting. The CB2-mediated effect is through macrophage-like Kupffer cells.

Conclusion: Our study suggests that the ConA-induced liver injury model in mice is protected by CB2 agonist AM1241 by modulation of CB2 receptor-rich immune cells, for example, Kupffer cells. Reduced inflammatory responses regulate apoptosis/cell death in the liver particularly hepatocytes and other parenchymal cells.
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http://dx.doi.org/10.1177/20587384211035251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366113PMC
August 2021

Shiquan Yuzhen Decoction inhibits angiogenesis and tumor apoptosis caused by non-small cell lung cancer and promotes immune response.

Am J Transl Res 2021 15;13(7):7492-7507. Epub 2021 Jul 15.

Department of Acupuncture and Moxibustion, Longhua Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200032, China.

Background: TCM treatment for lung carcinoma has been reported by many researches. Shiquan Yuzhen Decoction can be used in the clinical treatment of lung carcinoma, but its specific mechanism is still under exploration at present.

Methods: The active ingredients and mechanism of Shiquan Yuzhen Decoction on non-small cell lung carcinoma were discussed by network pharmacology. The main active ingredients, targets and disease genes of non-small cell lung carcinoma of Shiquan Yuzhen Decoction were screened through relevant databases. Lewis lung carcinoma bearing mice model was established by inoculating Lewis lung carcinoma cells to C57BL/6 mice under the right armpit. Different doses of Shiquan Yuzhen Decoction were used to observe the apoptosis and angiogenesis changes of tumor tissues in mice.

Results: A total of 26 key active compounds meeting the evaluation of generic properties and 182 main targets were screened out. The multi-level network model shows that Shiquan Yuzhen Decoction can regulate the target gene network of non-small cell lung carcinoma. And it can inhibit tumor growth in tumor-bearing mice, induce apoptosis of tumor cells, and evidently increase the activities of Caspase-3, 8 and 9. The dose of 17.4 g/kg can evidently inhibit the formation of microvessels in transplanted tumor tissues, improve the sensitivity of mice's diet and activities, increase the spleen index of tumor-bearing mice, and inhibit inflammatory factors.

Conclusion: Shiquan Yuzhen Decoction can evidently improve the quality of life of Lewis lung carcinoma-bearing mice and inhibit tumor growth in mice, which is a potential clinical treatment plan.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340251PMC
July 2021

Naloxone Protects against Lipopolysaccharide-Induced Neuroinflammation and Microglial Activation via Inhibiting ATP-Sensitive Potassium Channel.

Comput Math Methods Med 2021 29;2021:7731528. Epub 2021 Jul 29.

Department of Neurosurgery, Haimen People's Hospital, Nantong 226100, China.

Aim: The aim of this study was to evaluate the anti-inflammatory effects and underlying mechanism of naloxone on lipopolysaccharide- (LPS-) induced neuronal inflammation and microglial activation.

Methods: LPS-treated microglial BV-2 cells and mice were used to investigate the anti-inflammatory effects of naloxone.

Results: The results showed that naloxone dose-dependently promoted cell proliferation in LPS-induced BV-2 cells, downregulated the expression of proinflammatory cytokines (TNF-, IL-1, and IL-6) and proinflammatory enzymes iNOS and COX-2 as well as the expression of free radical molecule NO, and reduced the expression of Iba-1-positive microglia in LPS-stimulated BV-2 cells and mouse brain. Moreover, naloxone improved LPS-induced behavior degeneration in mice. Mechanically, naloxone inhibited LPS-induced activation in the ATP-sensitive potassium (KATP) channel. However, the presence of glibenclamide (Glib), an antagonist of KATP channel, ameliorated the suppressive effects of naloxone on inflammation and microglial activation.

Conclusion: Naloxone prevented LPS-induced neuroinflammation and microglial activation partially through the KATP channel. These findings might highlight the potential of naloxone in neuroinflammation therapy.
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http://dx.doi.org/10.1155/2021/7731528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349287PMC
July 2021

ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells.

Blood 2021 Aug 6. Epub 2021 Aug 6.

Rui-Jin hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Proper regulation of p53 signaling is critical for the maintenance of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The hematopoietic cell-specific mechanisms regulating p53 activity remain largely unknown. Here, we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and post-injury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with and thus inhibits the transcriptional activity of p53 in hematopoietic cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from chronic myelogenous leukemia (CML) patients. Anp32b deletion enhances p53 transcriptional activity to impair LSCs function in a murine CML model, and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B, and identify ANP32B as a potential therapeutic target in treating CML.
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http://dx.doi.org/10.1182/blood.2020010400DOI Listing
August 2021

Heat-induced gel properties and gastrointestinal digestive properties of egg white produced by hens fed with selenium-enriched yeast.

Food Chem 2022 Jan 27;366:130712. Epub 2021 Jul 27.

College of Food Sciences and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China. Electronic address:

The aim of this study was to investigate the effect of selenium enrichment on the gel properties and gastrointestinal digestive properties of egg white. Results of texture profile analysis, scanning electron microscopy and differential scanning calorimetry showed that the heat-induced gel of selenium-enriched egg white (EW-2) exhibited higher gel strength, smoother microstructure, and higher thermal denaturation temperature than ordinary egg white (EW-1), which might be due to the change of ovomucin and ovotransferrin content. The gastrointestinal digestive products of the EW-2 protein contained a higher proportion of small peptides and more free amino acids than those of EW-1. Results of oxygen radical absorbance capacity and cellular antioxidant activity assays indicated that digestive products of the EW-2 protein exhibited stronger antioxidant activity than those of the EW-1 protein. In summary, Se enrichment improved heat-induced gel properties of egg white, and promoted the gastrointestinal digestion of egg white protein.
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http://dx.doi.org/10.1016/j.foodchem.2021.130712DOI Listing
January 2022

Reducing Water Activity by Zeolite Molecular Sieve Membrane for Long-Life Rechargeable Zinc Battery.

Adv Mater 2021 Sep 2;33(38):e2102415. Epub 2021 Aug 2.

Energy Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Umezono, Tsukuba, 305-8568, Japan.

Aqueous electrolytes offer major advantages in safe battery operation, green economy, and low production cost for advanced battery technology. However, strong water activity in aqueous electrolytes provokes a hydrogen evolution reaction and parasitic passivation on electrodes, leaving poor ion-transport in the electrolyte/electrode interface. Herein, a zeolite molecular sieve-modified (zeolite-modified) aqueous electrolyte is proposed to reduce water activity and its side-reaction. First, Raman spectroscopy reveals a highly aggressive solvation configuration and significantly suppressed water activity toward single water molecule. Then less hydrogen evolution and anti-corrosion ability of zeolite-modified electrolyte by simulation and electrochemical characterizations are identified. Consequently, a zinc (Zn) anode involves less side-reaction, and develops into a compact deposition morphology, as proved by space-resolution characterizations. Moreover, zeolite-modified electrolyte favors cyclic life of symmetric Zn||Zn cells to 4765 h at 0.8 mA cm , zinc-VO coin cell to 3000 cycles, and pouch cell to 100 cycles. Finally, the mature production technique and low-cost of zeolite molecular sieve would tremendously favor the future scale-up application in engineering aspect.
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http://dx.doi.org/10.1002/adma.202102415DOI Listing
September 2021

Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal.

Stem Cells Int 2021 10;2021:5522723. Epub 2021 Jul 10.

Laboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, China.

Dax1(also known as Nr0b1) is regarded as an important component of the transcription factor network in mouse embryonic stem cells (ESCs). However, the role and the molecular mechanism of Dax1 in the maintenance of different pluripotency states are poorly understood. Here, we constructed a stable Dax1 knockout (KO) cell line using the CRISPR/Cas9 system to analyze the precise function of Dax1. We reported that 2i/LIF-ESCs had significantly lower Dax1 expression than LIF/serum-ESCs. Dax1KO ES cell lines could be established in 2i/LIF and their pluripotency was confirmed. In contrast, Dax1-null ESCs could not be continuously passaged in LIF/serum due to severe differentiation and apoptosis. In LIF/serum, the activities of the Core module and Myc module were significantly reduced, while the PRC2 module was activated after Dax1KO. The expression of most proapoptotic genes and lineage-commitment genes were drastically increased, while the downregulated expression of antiapoptotic genes and many pluripotency genes was observed. Our research on the pluripotent state-dependent role of Dax1 provides clues to understand the molecular regulation mechanism at different stages of early embryonic development.
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http://dx.doi.org/10.1155/2021/5522723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286181PMC
July 2021
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