Publications by authors named "Li Cao"

861 Publications

Genetic Incorporation of  ε-N-benzoyllysine by Engineering Methanomethylophilus alvus Pyrrolysyl-tRNA Synthetase.

Chembiochem 2021 Jun 12. Epub 2021 Jun 12.

University of California San Francisco, Pharmaceutical Chemistry, 555 Mission Bay Blvd South, 94158, San Francisco, UNITED STATES.

Protein post-translational modifications regulate protein structure and function. Lysine benzoylation is a new type of histone mark with unique physiological relevance. To construct proteins with this modification site-specifically introduced, here we generated orthogonal tRNA Pyl -MaBzKRS pairs by engineering  Methanomethylophilus alvus  pyrrolysyl-tRNA synthetase, allowing the genetic incorporation of ε-N-benzoyllysine (BzK) into proteins with high efficiency in  E. coli  and mammalian cells. Two types of MaBzKRS were identified to incorporate BzK using mutations located at different positions of the amino acid binding pocket. These MaBzKRS are small in size and highly expressed, which will afford broad utilities in studying the biological effects of lysine benzoylation.
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http://dx.doi.org/10.1002/cbic.202100218DOI Listing
June 2021

A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease.

Mol Med Rep 2021 Aug 10;24(2). Epub 2021 Jun 10.

Department of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

Alexander disease (AxD) is a cerebral white matter disease affecting a wide range of ages, from infants to adults. In the present study, two cases of bulbospinal form AxD were reported, and a preliminary exploration of AxD was conducted thorough clinical, functional magnetic resonance imaging (fMRI) and functional analyses. In total, two de novo mutations in the glial fibrillary acidic protein () gene (c.214G>A and c.1235C>T) were identified in unrelated patients (one in each patient). Both patients showed increased regional neural activity and functional connectivity in the cerebellum and posterior parietal cortex according to fMRI analysis. Notably, grey matter atrophy was discovered in the patient with c.214G>A variant. Functional experiments revealed aberrant accumulation of mutant GFAP and decreased solubility of c.1235C>T variant. Under pathological conditions, autophagic flux was activated for GFAP aggregate degradation. Moreover, transcriptional data of AxD and healthy human brain samples were obtained from the Gene Expression Omnibus database. Gene set enrichment analysis revealed an upregulation of immune‑related responses and downregulation of ion transport, synaptic transmission and neurotransmitter homeostasis. Enrichment analysis of cell‑specific differentially expressed genes also indicated a marked inflammatory environment in AxD. Overall, the clinical features of the two patients with bulbospinal form AxD were thoroughly described. To the best of our knowledge, the brain atrophy pattern and spontaneous brain functional network activity of patients with AxD were explored for the first time. Cytological experiments provided evidence of the pathogenicity of the identified variants. Furthermore, bioinformatics analysis found that inflammatory immune‑related reactions may play a critical role in AxD, which may be conducive to the understanding of this disease.
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http://dx.doi.org/10.3892/mmr.2021.12211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201446PMC
August 2021

A chitosan/mesoporous silica nanoparticle-based anticancer drug delivery system with a "tumor-triggered targeting" property.

Int J Biol Macromol 2021 Jun 7;183:2017-2029. Epub 2021 Jun 7.

Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, Hubei University, Wuhan 430062, China. Electronic address:

To enhance drug utilization and reduce their side effects, the strategy of "tumor-triggered targeting" was introduced to fabricate dual-pH-sensitive chitosan (CHI)/mesoporous silica nanoparticle (MSN)-based anticancer drug delivery system (DDS) in this work. Model drug doxorubicin hydrochloride (DOX) was loaded in MSN, which was modified with benzimidazole (Bz) group. Then chitosan-graft-β-cyclodextrin (CHI-g-CD) was applied as the "gatekeeper" to cover MSN through host-guest interaction between β-CD and Bz. After being coated with targeting peptide adamantane-glycine-arginine-glycine-aspartic acid-serine (Ad-GRGDS), methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) was finally grafted on CHI through the pH-sensitive benzoic imine bond. Due to the dynamic protection of PEG, the obtained carriers were "stealthy" at pH 7.4, but could reveal the shielded targeting peptide and the positive charge of CHI in the weakly acidic environment achieved a "tumor-triggered targeting". Inside cancer cells, the interaction between β-CD and Bz group could be destroyed due to the lower pH, resulted in DOX release. Both in vitro and in vivo studies proved the DDS could targeting induce cancer cell apoptosis, inhibit tumor growth, and reduce the cytotoxicity of DOX against normal cells. It is expected that the system named [email protected] could be a potential choice for cancer therapy.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.004DOI Listing
June 2021

Pore engineering of ultrathin covalent organic framework membranes for organic solvent nanofiltration and molecular sieving.

Chem Sci 2020 Apr 30;11(21):5434-5440. Epub 2020 Apr 30.

Division of Physical Science and Engineering, King Abdullah University of Science and Technology (KAUST) Thuwal 23955-6900 Saudi Arabia

The advantages of two dimensional covalent organic framework membranes to achieve high flux have been demonstrated, but the capability of easy structural modification to manipulate the pore size has not been fully explored yet. Here we report the use of the Langmuir-Blodgett method to synthesize two ultrathin covalent organic framework membranes ( and ) that have a similar framework structure to our previously reported covalent organic framework membrane () but different lengths of carbon chains aiming to rationally control the pore size. The membrane permeation results in the applications of organic solvent nanofiltration and molecular sieving of organic dyes showed a systematic shift of the membrane flux and molecular weight cut-off correlated to the pore size change. These results enhanced our fundamental understanding of transport through uniform channels at nanometer scales. Pore engineering of the covalent organic framework membranes was demonstrated for the first time.
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http://dx.doi.org/10.1039/d0sc01679aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159406PMC
April 2020

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway.

Neurosci Bull 2021 Jun 6. Epub 2021 Jun 6.

Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain Science, Naval Medical University, Shanghai, 200433, China.

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
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http://dx.doi.org/10.1007/s12264-021-00696-7DOI Listing
June 2021

Tight covalent organic framework membranes for efficient anion transport via molecular precursor engineering.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Tianjin University, School of Chemical Engineering and Technology, Weijin Road, 300072, Tianjin, CHINA.

Fabricating covalent organic frameworks (COFs) membranes with tight structure, which can fully utilize well-defined framework structure and thus achieve superior conduction performance, remains a grand challenge. Herein, through molecular precursor engineering of COFs, we reported the fabrication of tight COFs membrane with the ever-reported highest hydroxide ion conductivity over 200 mS cm-1 at 80 °C, 100% RH. Six quaternary ammonium-functionalized COFs were synthesized by assembling functional hydrazides and different aldehyde precursors. In an organic-aqueous reaction system, the impact of the aldehyde precursors with different size, electrophilicity and hydrophilicity on the reaction-diffusion process for fabricating COFs membranes was elucidated. Particularly, more hydrophilic aldehydes were prone to push the reaction zone from the interface region to the aqueous phase of the reaction system, the tight membranes were thus fabricated via phase-transfer polymerization process, conferring around 4~8 times the anion conductivity over the loose membranes via interfacial polymerization process.
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http://dx.doi.org/10.1002/anie.202105190DOI Listing
June 2021

A Single-Domain Antibody-Based Anti-PSMA Recombinant Immunotoxin Exhibits Specificity and Efficacy for Prostate Cancer Therapy.

Int J Mol Sci 2021 May 23;22(11). Epub 2021 May 23.

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.

Prostate cancer (PCa) is the second most common cancer in men, causing more than 300,000 deaths every year worldwide. Due to their superior cell-killing ability and the relative simplicity of their preparation, immunotoxin molecules have great potential in the clinical treatment of cancer, and several such molecules have been approved for clinical application. In this study, we adopted a relatively simple strategy based on a single-domain antibody (sdAb) and an improved exotoxin A (PE) toxin (PE24X7) to prepare a safer immunotoxin against prostate-specific membrane antigen (PSMA) for PCa treatment. The designed anti-PSMA immunotoxin, JVM-PE24X7, was conveniently prepared in its soluble form in an () system, avoiding the complex renaturation process needed for immunotoxin preparation by the conventional strategy. The product was very stable and showed a very strong ability to bind the PSMA receptor. Cytotoxicity assays showed that this molecule at a very low concentration could kill PSMA-positive PCa cells, with an EC value (concentration at which the cell viability decreased by 50%) of 15.3 pM against PSMA-positive LNCaP cells. Moreover, this molecule showed very good killing selectivity between PSMA-positive and PSMA-negative cells, with a selection ratio of more than 300-fold. Animal studies showed that this molecule at a very low dosage (5 × 0.5 mg/kg once every three days) completely inhibited the growth of PCa tumors, and the maximum tolerable dose (MTD) was more than 15 mg/kg, indicating its very potent tumor-treatment ability and a wide therapeutic window. Use of the new PE toxin, PE24X7, as the effector moiety significantly reduced off-target toxicity and improved the therapeutic window of the immunotoxin. The above results demonstrate that the designed anti-PSMA immunotoxin, JVM-PE24X7, has good application value for the treatment of PCa.
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http://dx.doi.org/10.3390/ijms22115501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197099PMC
May 2021

Scalable fabrication of crystalline COF membrane from amorphous polymeric membrane.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Tianjin University, School of Chemical Engineering and Technology, Weijin Road, 300072, Tianjin, CHINA.

Covalent organic framework (COF) membranes hold tremendous potential for widespread applicability, but their scalable fabrication remains challenging. Here, we demonstrate the disorder-to-order transformation from amorphous polymeric membrane to crystalline COF membrane via monomer exchange. Solution-processing method is used to prepare amorphous membranes and the replacing monomer is selected based on the chemical and thermodynamical stability of the final framework. Afterwards, the reversible imine bonds allow the extraneous monomers to replace the pristine monomers within amorphous membrane, driving the transformation from disordered network to ordered framework. The incorporation of intramolecular hydrogen bonds enables the crystalline COF to imprint the morphology of amorphous membrane. The COF membranes harvest proton conductivity up to 0.53 S cm -1 at 80 °C. Our strategy builds a bridge between amorphous polymeric and crystalline COF membranes, not only paving the way to large-scale fabrication of COF membranes, but also affording some guidance on materials processing via disorder-to-order transformation.
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http://dx.doi.org/10.1002/anie.202102965DOI Listing
June 2021

Discovery of the signal pathways and major bioactive compounds responsible for the anti-hypoxia effect of Chinese cordyceps.

J Ethnopharmacol 2021 Sep 24;277:114215. Epub 2021 May 24.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510260, China. Electronic address:

Ethnopharmacological Relevance: Hypoxia will cause an increase in the rate of fatigue and aging. Chinese cordyceps, a parasitic Thitarodes insect-Ophiocordyceps sinensis fungus complex in the Qinghai-Tibet Plateau, has long been used to ameliorate human conditions associated with aging and senescence, it is principally applied to treat fatigue, night sweating and other symptoms related to aging, and it may play the anti-aging and anti-fatigue effect by improving the body's hypoxia tolerance.

Aims Of The Study: The present study investigated the anti-hypoxia activity of Chinese cordyceps and explore the main corresponding signal pathways and bioactive compounds.

Materials And Methods: In this study, network pharmacology analysis, molecular docking, cell and whole pharmacodynamic experiments were hired to study the major signal pathways and the bioactive compounds of Chinese cordyceps for anti-hypoxia activity.

Results: 17 pathways which Chinese cordyceps acted on seemed to be related to the anti-hypoxia effect, and "VEGF signal pathway" was one of the most important pathway. Chinese cordyceps improved the survival rate and regulated the targets related VEGF signal pathway of H9C2 cells under hypoxia, and also had significant anti-hypoxia effects to mice. Chorioallantoic membrane model experiment showed that Chinese cordyceps and the main constituents of (9Z,12Z)-octadeca-9,12-dienoic acid and cerevisterol had significant angiogenic activity in hypoxia condition.

Conclusion: Based on the results of network pharmacology and molecular docking analysis, cell and whole pharmacodynamic experiments, promoting angiogenesis by regulating VEGF signal pathway might be one of the mechanisms of anti-hypoxia effect of Chinese cordyceps, (9Z, 12Z)-octadeca-9,12-dienoic acid and cerevisterol were considered as the major anti-hypoxia bioactive compounds in Chinese cordyceps.
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http://dx.doi.org/10.1016/j.jep.2021.114215DOI Listing
September 2021

A study of breastfeeding practices, SARS-CoV-2 and its antibodies in the breast milk of mothers confirmed with COVID-19.

Lancet Reg Health West Pac 2020 Nov 10;4:100045. Epub 2020 Nov 10.

Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei 430070, China.

Background: The possibility of 2019 novel coronavirus disease (COVID-19) transmission to neonates through breast milk remains unverified.

Methods: This paper presents the interim results of a longitudinal study being carried out in Hubei province. As of 1 April 2020, 24 mothers confirmed with COVID-19, 19 mothers suspected with COVID-19 but Polymerase chain reaction negative, and 21 mothers without COVID-19 and their neonates have been recruited. Telephone follow-up was conducted to collect information on breastfeeding practices. Forty-four breast milk samples were collected from 16 of the 24 mothers with confirmed COVID-19 for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) ribonucleic acid (RNA) and antibodies (IgM and IgG) testing.

Findings: The average mother-child separation time was 36•7 ± 21•1 days among mothers confirmed with COVID-19, significantly longer than that of the suspected group (16•6 ± 13•1 days) and control group (10•5 ± 8•2 days). Both the COVID-19 confirmed (58•3%) and suspected (52•6%) groups presented significantly lower rates of breastfeeding as compared with the control group (95•2%). All 44 breast milk samples tested negative for the SARS-CoV-2 nucleic acid. Thirty-eight breast milk samples underwent antibody testing and all tested negative for IgG. Twenty-one breast milk samples from 8 women tested positive for IgM, while the remaining samples from 11 women tested negative.

Interpretation: Considering the lack of evidence for SARS-CoV-2 transmission through breast milk, breastfeeding counselling along with appropriate hand hygiene precautions and facemasks should be provided to all pregnant women.

Funding: The study was funded by the Hong Kong Committee for UNICEF.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654387PMC
November 2020

Novel Mutations in Chinese Patients with Multiple Osteochondromas Identified Using Whole Exome Sequencing.

Genet Test Mol Biomarkers 2021 May;25(5):361-367

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Multiple osteochondromas (MO) are an autosomal-dominant disease characterized by the growth of multiple cartilage-capped prominences in the growth plate region of the metaphysis in long and flat bones. To detect genetic mutations related to MO, a three-generation Chinese family with MO was evaluated using whole exome sequencing for mutation screening. The candidate pathogenic mutation was validated by Sanger sequencing. A novel frameshift (NM_000401.3:c.1321del:p.Leu441TrpfsTer28) in exon 8 of the exotosin 2 () gene was identified in two affected individuals. Codons 441 and 468 in the gene are highly conserved among vertebrates as demonstrated by multiple sequence alignment. The c.1321 del C resulted in an amino acid change at codon 441, which generated a premature stop codon at position 468, causing complete loss of the glycosyltransferase domain. A novel frameshift mutation c.1321delC detected in the gene may help in prenatal genetic screening and early diagnosis of MO.
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http://dx.doi.org/10.1089/gtmb.2020.0317DOI Listing
May 2021

High-sensitivity operation of a single-beam atomic magnetometer for three-axis magnetic field measurement.

Opt Express 2021 May;29(10):15641-15652

We demonstrate a single-beam atomic magnetometer (AM) capable of measuring a three-axis magnetic field with high-sensitivity, achieved by applying a small DC offset field and a high frequency modulation field. To satisfy the miniaturization demand of AMs, an elliptically polarized light detuned by 50 GHz from the resonance transition center is employed. The circularly polarized component is used to polarize the alkali-metal atoms, while the linearly polarized light is used to detect the dynamics of the polarized spin under a magnetic field. Based on theoretical analysis, parameters that significantly affect the performance are optimized, and a sensitivity of 20 fT/Hz in x-axis, 25 fT/Hz in y-axis, 30 fT/Hz in z-axis is achieved with a miniature 4 × 4 × 4 mm Rb vapor cell. Moreover, we also verify that the operation principle of AMs can be used to null background magnetic fields in-situ with isotropic compensation resolution of 6.7 pT, which provides an effectively precise method for zeroing ambient magnetic field. The high-sensitivity operating of an elliptically-polarized-laser-based magnetometer provides prospective futures for constructing a compact, low-cost AM, which is particularly applicable for non-invasive bio-magnetic imaging such as array-based magnetoencephalography (MEG) and magnetocardiography (MCG).
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http://dx.doi.org/10.1364/OE.425851DOI Listing
May 2021

Correction to: Disrupted intraflagellar transport due to IFT74 variants causes Joubert syndrome.

Genet Med 2021 Jun;23(6):1175

Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1038/s41436-021-01191-0DOI Listing
June 2021

Computerized Symbol Digit Modalities Test in a Swiss Pediatric Cohort Part 1: Validation.

Front Psychol 2021 22;12:631536. Epub 2021 Apr 22.

Division of Child Neurology, Department of Pediatrics, University Children's Hospital Bern, University of Bern, Bern, Switzerland.

Objective: The objective of this study was to validate the computerized Symbol Digit Modalities Test (c-SDMT) in a Swiss pediatric cohort, in comparing the Swiss sample to the Canadian norms. Secondly, we evaluated sex effects, age-effects, and test-retest reliability of the c-SDMT in comparison to values obtained for the paper and pencil version of the Symbol Digit Modalities Test (SDMT).

Methods: This longitudinal observational study was conducted in a single-center setting at the University Children's Hospital of Bern. Our cohort consisted of 86 children (45 male and 41 female) aged from 8 to 16 years. The cohort included both healthy participants ( = 38) and patients ( = 48) hospitalized for a non-neurological disease. Forty eight participants were assessed during two testing sessions with the SDMT and the c-SDMT.

Results: Test-retest reliability was high in both tests (SDMT: ICC = 0.89, c-SDMT: ICC = 0.90). A reliable change index was calculated for the SDMT (RCIp = -3.18, 14.01) and the c-SDMT (RCIp = -5.45, 1.46) corrected for practice effects. While a significant age effect on information processing speed was observed, no such effect was found for sex. When data on the c-SDMT performance of the Swiss cohort was compared with that from a Canadian cohort, no significant difference was found for the mean time per trial in any age group. Norm values for age groups between 8 and 16 years in the Swiss cohort were established.

Conclusion: Norms for the c-SDMT between the Swiss and the Canadian cohort were comparable. The c-SDMT is a valid alternative to the SDMT. It is a feasible and easy to administer bedside tool due to high reliability and the lack of motor demands.
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http://dx.doi.org/10.3389/fpsyg.2021.631536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101631PMC
April 2021

Computerized Symbol Digit Modalities Test in a Swiss Pediatric Cohort - Part 2: Clinical Implementation.

Front Psychol 2021 23;12:631535. Epub 2021 Apr 23.

Division of Child Neurology, Department of Pediatrics, University Children's Hospital Bern, University of Bern, Bern, Switzerland.

Background: Information processing speed (IPS) is a marker for cognitive function. It is associated with neural maturation and increases during development. Traditionally, IPS is measured using paper and pencil tasks requiring fine motor skills. Such skills are often impaired in patients with neurological conditions. Therefore, an alternative that does not need motor dexterity is desirable. One option is the computerized symbol digit modalities test (c-SDMT), which requires the patient to verbally associate numbers with symbols.

Methods: Eighty-six participants (8-16 years old; 45 male; 48 inpatients) were examined, 38 healthy and 48 hospitalized for a non-neurological disease. All participants performed the written SDMT, c-SDMT, and the Test of Non-verbal Intelligence Fourth Edition (TONI-4). Statistical analyses included a multivariate analysis of covariance (MANCOVA) for the effects of intelligence (IQ) and hospitalization on the performance of the SDMT and c-SDMT. A repeated measures analysis of variance (repeated measures ANOVA) was used to compare performance across c-SDMT trials between inpatients and outpatients.

Results: The MANCOVA showed that hospitalization had a significant effect on IPS when measured with the SDMT ( = 0.04) but not with the c-SDMT ( = 0.68), while IQ ( = 0.92) had no effect on IPS. Age ( < 0.001) was the best predictor of performance of both tests. The repeated measures ANOVA revealed no significant difference in within-test performance ( = 0.06) between outpatient and inpatient participants in the c-SDMT.

Conclusion: Performance of the c-SDMT is not confounded by hospitalization and gives within-test information. As a valid and reliable measure of IPS for children and adolescents, it is suitable for use in both inpatient and outpatient populations.
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http://dx.doi.org/10.3389/fpsyg.2021.631535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102725PMC
April 2021

GGC repeat expansions in NOTCH2NLC causing a phenotype of distal motor neuropathy and myopathy.

Ann Clin Transl Neurol 2021 Jun 4;8(6):1330-1342. Epub 2021 May 4.

Department of Neurology, Peking University First Hospital, Beijing, 100034, China.

Background: The expansion of GGC repeat in the 5' untranslated region of the NOTCH2NLC has been associated with various neurogenerative disorders of the central nervous system and, more recently, oculopharyngodistal myopathy. This study aimed to report patients with distal weakness with both neuropathic and myopathic features on electrophysiology and pathology who present GGC repeat expansions in the NOTCH2NLC.

Methods: Whole-exome sequencing (WES) and long-read sequencing were implemented to identify the candidate genes. In addition, the available clinical data and the pathological changes associated with peripheral nerve and muscle biopsies were reviewed and studied.

Results: We identified and validated GGC repeat expansions of NOTCH2NLC in three unrelated patients who presented with progressive weakness predominantly affecting distal lower limb muscles, following negative results in an initial WES. We found intranuclear inclusions with multiple proteins deposits in the nuclei of both myofibers and Schwann cells. The clinical features of these patients are compatible with the diagnosis of distal motor neuropathy and rimmed vacuolar myopathy.

Interpretation: These phenotypes enrich the class of features associated with NOTCH2NLC-related repeat expansion disorders (NRED), and provide further evidence that the neurological symptoms of NRED include not only brain, spinal cord, and peripheral nerves damage, but also myopathy, and that overlapping symptoms might exist.
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http://dx.doi.org/10.1002/acn3.51371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164861PMC
June 2021

Mechanisms of action of ribosomally synthesized and posttranslationally modified peptides (RiPPs).

J Ind Microbiol Biotechnol 2021 Jun;48(3-4)

Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.

Natural products remain a critical source of medicines and drug leads. One of the most rapidly growing superclasses of natural products is RiPPs: ribosomally synthesized and posttranslationally modified peptides. RiPPs have rich and diverse bioactivities. This review highlights examples of the molecular mechanisms of action that underly those bioactivities. Particular emphasis is placed on RiPP/target interactions for which there is structural information. This detailed mechanism of action work is critical toward the development of RiPPs as therapeutics and can also be used to prioritize hits in RiPP genome mining studies.
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http://dx.doi.org/10.1093/jimb/kuab005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183687PMC
June 2021

Gut Bacterial and Fungal Communities of the Wild and Laboratory-Reared Larvae, Host of the Chinese Medicinal Fungus on Tibetan Plateau.

Insects 2021 Apr 7;12(4). Epub 2021 Apr 7.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510260, China.

By employing a culture-dependent and -independent 16S rRNA and ITS gene high-throughput sequencing analyses, comprehensive information was obtained on the gut bacterial and fungal communities in the ghost moth larvae of three different geographic locations from high-altitude on Tibet plateau and from low-altitude laboratory. Twenty-six culturable bacterial species belonging to 21 genera and 14 fungal species belonging to 12 genera were identified from six populations by culture-dependent method. was the most abundant bacterial species from both the wild and laboratory-reared larvae. The most abundant OTUs in the wild ghost moth populations were Carnobacteriaceae, Enterobacteriaceae for bacteria, and Ascomycota and Basidiomycota for fungi. Larval microbial communities of the wild ghost moth from different geographic locations were not significantly different from each other but significant difference in larval microbial community was detected between the wild and laboratory-reared ghost moth. The larval gut of the wild ghost moth was dominated by the culturable . However, that of the laboratory-reared ghost moth exhibited significantly abundant , , , and . Furthermore, the larval gut of the wild ghost moth had a significantly higher abundance of but lower abundance of and than that of the laboratory-reared ghost moth.
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http://dx.doi.org/10.3390/insects12040327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067570PMC
April 2021

Baseline and momentary predictors of ecological momentary assessment adherence in a sample of adults with binge-eating disorder.

Eat Behav 2021 Apr 20;41:101509. Epub 2021 Apr 20.

Sanford Center for Bio-behavioral Research, Fargo, ND, United States of America; Department of Psychiatry, University of North Dakota School of Medicine and Health Sciences, Fargo, ND, United States of America.

Ecological Momentary Assessment (EMA) is a widely used methodology to examine psychological and behavioral phenomena among individuals with eating disorders (EDs). While EMA overcomes limitations associated with traditional retrospective self-report, it remains subject to potential methodological limitations, including poor adherence to the EMA protocol, which may bias findings. Little is known about baseline and momentary predictors of missing EMA data in ED research; however, such work may help clarify the correlates of missingness and illuminate steps to address potential bias. The purpose of this study was to investigate predictors of EMA adherence in a sample of adults with binge-eating disorder (BED) enrolled in a randomized treatment trial. Prior to treatment, 110 patients completed self-report questionnaires assessing demographics, psychopathology, and transdiagnostic risk/maintenance factors. Participants then responded to EMA questions regarding their eating behavior and internal states six times a day for seven days. A series of generalized-linear and mixed-effect models were conducted to examine baseline and momentary predictors of EMA adherence. No significant baseline predictors were identified, suggesting that participants' overall level of missing data was not related to person-level characteristics (e.g., gender, level of ED pathology). However, lower positive affect, lower hunger, signals later in the day, later days in the EMA protocol, and missed prior signals predicted greater odds of signal non-response, suggesting certain contextual factors may impact the likelihood that a participant with BED will respond to the subsequent EMA signal. Ultimately, these findings have implications for future eating disorder EMA research.
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http://dx.doi.org/10.1016/j.eatbeh.2021.101509DOI Listing
April 2021

Microbial Metabolite Sodium Butyrate Attenuates Cartilage Degradation by Restoring Impaired Autophagy and Autophagic Flux in Osteoarthritis Development.

Front Pharmacol 2021 9;12:659597. Epub 2021 Apr 9.

Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Osteoarthritis (OA) is a degenerative joint disease with multiple etiologies that affects individuals worldwide. No effective interventions are currently available to reverse the pathological process of OA. Sodium butyrate (NaB), a component of short-chain fatty acids (SCFAs), has multiple biological activities, including the attenuation of inflammation and anti-tumor activities in various diseases. However, whether the protective effects of NaB in OA are associated with the promotion of autophagy had not been investigated. Here, we explored the chondroprotective properties of NaB in an interleukin (IL)-1β-induced inflammatory chondrocyte model and an anterior cruciate ligament transection (ACLT) mouse model. Hematoxylin and eosin (HE), Safranin O, and immunohistochemical staining were performed to evaluate the effects of NaB treatment on articular cartilage. An optimal NaB dose for chondrocyte treatment was determined cell counting kit-8 assays. Immunofluorescence and transmission electron microscopy were used to detect autophagy in chondrocytes. Flow cytometry was utilized to detect reactive oxygen species (ROS), cell cycle activity, and apoptosis in chondrocytes. Western blot and immunostaining were performed to evaluate the protein expression levels of relevant indicators. We found that the administration of NaB by oral gavage could attenuate cartilage degradation. In parallel, NaB treatment could enhance the activation of autophagy, increase autophagic flux, decrease extracellular matrix degradation, and reduce apoptosis by restraining inflammation, ROS production, and cell cycle arrest in IL-1β-treated chondrocytes. The protective effects of NaB could be partially abolished by the autophagy inhibitor 3-methyladenine (3-MA), which indicated that the protective effects of NaB against OA were partially governed by the enhancement of autophagy to restrain the formation of inflammatory mediators and ROS and regulate cell cycle progression and apoptosis in chondrocytes. In conclusion, NaB could attenuate OA progression by restoring impaired autophagy and autophagic flux the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, both and , implying that NaB could represent a novel therapeutic approach for OA.
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http://dx.doi.org/10.3389/fphar.2021.659597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062861PMC
April 2021

Analysis of metastasis and survival between extrahepatic and intrahepatic cholangiocarcinoma: A large population-based study.

Medicine (Baltimore) 2021 Apr;100(16):e25635

Department of Infection Prevention and Control, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China.

Abstract: To date, extrahepatic cholangiocarcinoma (ECCA) and intrahepatic cholangiocarcinoma (ICCA) have rarely been compared; therefore, we attempted to learn more about the rates of metastasis and survival in both ICCA and ECCA.Data of patients in the SEER database diagnosed with ICCA or ECCA were extracted to analyse the rate of metastasis and survival. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for metastasis. Propensity score matching (PSM) was used to compare survival rates between ECCA and ICCA.Data from a total of 15,751 patients diagnosed with ICCA or ECCA were extracted to analyse the rate of metastasis. Metastasis was more common in ECCA than ICCA (42.62% vs. 31.46%, P < .05), while ICCA in the T1 stage had a lower rate of metastasis (25.35% vs. 30.61%, P < .05). Age, pathology grade, tumour size, lymph node metastasis and T stage were independent risk factors for metastasis in both ECCA and ICCA. There was an inverse correlation between age and metastasis in both ICCA and ECCA. Moreover, PSM demonstrated that patients with ECCA had a better prognosis than patients with ICCA. Patients with ICCA in the T1 stage had better survival than those with ECCA in the T1 stage.Our study was the first to compare the rates of metastasis and survival between ECCA and ICCA. We observed an inverse association between age and metastasis, that patients with ECCA had a better prognosis than patients with ICCA, and that patients with ECCA in the T1 stage had worse survival than patients with ICCA in the T1 stage.
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http://dx.doi.org/10.1097/MD.0000000000025635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078350PMC
April 2021

Association of Body Mass Index With Somatic Mutations in Breast Cancer.

Front Oncol 2021 1;11:613933. Epub 2021 Apr 1.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: The relationship between body mass index (BMI) and the prognosis or treatment response in patients with breast cancer has been demonstrated in previous studies, but the somatic mutation profiles in breast cancer patients with different BMIs have not been explored.

Methods: In the present study, the somatic mutation profiles in 421 female breast cancer patients who were stratified into three subgroups based on BMI (normal weight, overweight/obese, and underweight) were investigated. Capture-based targeted sequencing was performed using a panel comprising 520 cancer-related genes.

Results: A total of 3547 mutations were detected in 390 genes. In breast cancer patients with different BMI statuses, the tumors exhibited high mutation frequency and burden. was the most common gene in the three groups, followed by , , and Meanwhile, the mutation hotspots in and were the same in the three BMI groups. More mutations were identified in underweight patients than those in normal patients. Except for , differentially mutated genes in postmenopausal patients were completely different from those in premenopausal patients. The distribution of mutation types was significantly different among BMI groups in the postmenopausal group. Underweight patients in the postmenopausal group harbored more mutations, more amplifications, and more mutations in genes involved in the WNT signaling pathway.

Conclusions: Our next-generation sequencing (NGS)-based gene panel analysis revealed the gene expression profiles of breast cancer patients with different BMI statuses. Although genes with high mutation frequency and burden were found in different BMI groups, some subtle differences could not be ignored. mutations might play a vital role in the progression of breast cancer in underweight patients, and this needs further analysis. Postmenopausal underweight patients with breast cancer have more aggressive characteristics, such as mutations, more amplifications, and more mutations in genes involved in the WNT signaling pathway. This study provides new evidence for understanding the characteristics of breast cancer patients with different BMIs.
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http://dx.doi.org/10.3389/fonc.2021.613933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049504PMC
April 2021

SM22 Loss Contributes to Apoptosis of Vascular Smooth Muscle Cells via Macrophage-Derived circRasGEF1B.

Oxid Med Cell Longev 2021 16;2021:5564884. Epub 2021 Mar 16.

Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang, Hebei 050017, China.

Vascular smooth muscle cell (VSMC) apoptosis is a major defining feature of abdominal aortic aneurysm (AAA) and mainly caused by inflammatory cell infiltration. Smooth muscle (SM) 22 prevents AAA formation through suppressing NF-B activation. However, the role of SM22 in VSMC apoptosis is controversial. Here, we identified that SM22 loss contributed to apoptosis of VSMCs via activation of macrophages. Firstly, deficiency of SM22 enhanced the interaction of VSMCs with macrophages. Macrophages were retained and activated by VSMCs via upregulating VCAM-1 expression. The ratio of apoptosis was increased by 1.62-fold in VSMCs treated with the conditional media (CM) from activated RAW264.7 cells, compared to that of the control CM ( < 0.01), and apoptosis of VSMCs was higher than that of WT VSMCs ( < 0.001). Next, circRasGEF1B from activated macrophages was delivered into VSMCs promoting ZFP36 expression via stabilization of ZFP36 mRNA. Importantly, circRasGEF1B, as a scaffold, guided ZFP36 to preferentially bind to and decay Bcl-2 mRNA in a sequence-specific manner and triggered apoptosis of VSMCs, especially in VSMCs. These findings reveal a novel mechanism by which the circRasGEF1B-ZFP36 axis mediates macrophage-induced VSMC apoptosis via decay of Bcl-2 mRNA, whereas VSMCs have a higher sensitivity to apoptosis.
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http://dx.doi.org/10.1155/2021/5564884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026322PMC
June 2021

[A cadaveric experimental study on domestic robot-assisted total knee arthroplasty].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Apr;35(4):409-413

Department of Orthopedics, the First Medical Center of Chinese PLA General Hospital, Beijing, 100853, P.R.China.

Objective: To simulate and validate the performance, accuracy, and safety of the Yuanhua robotic-assisted total knee arthroplasty system (YUANHUA-TKA) through cadaver-based experiment, thus optimizing the robotic system for the future human clinical application.

Methods: Six unilateral adult cadaver specimens of the lower limbs were scanned by three-dimensional CT before the experiment, and then the three-dimensional models of femur and tibia were obtained by using the preoperative software of YUANHUA-TKA system, so as to plan the type of prosthesis implant, the osteotomy volume and osteotomy angles [hip-knee-ankle angle (HKA), coronal frontal femoral component (FFC) and frontal tibial component (FTC)], the ideal value of HKA was set to 180°, and of FFC and FTC were set to 90°, respectively. The operator could further confirm the osteotomy plan according to the intraoperative situation before osteotomy, and then install the prosthesis after completing the osteotomy in each plane with the assistance of YUANHUA-TKA system. At last, the X-ray films of hip joint, knee joint, and ankle joint were taken and stitched into the full length X-ray film of the lower limb, and HKA, coronal FFC and FTC were measured.

Results: During the experiment, YUANHUA-TKA system ran stably. All sections of femur and tibia were smooth and no ligament injury was found. After operation, the HKA was 177.1°-179.7°, FFC was 87.9°-91.4°, and FTC was 87.3°-91.4°, which were within ±3° from the ideal values of preoperative planning.

Conclusion: The YUANHUA-TKA system can assist the surgeon to carry out precise osteotomy according to the preoperative planned value, which has a good auxiliary effect for total knee arthroplasty. It is expected to assist joint surgeons to improve the surgical accuracy in clinical application.
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http://dx.doi.org/10.7507/1002-1892.202010021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171615PMC
April 2021

Characterization of AKT Somatic Mutations in Chinese Breast Cancer Patients.

Cancer Manag Res 2021 7;13:3055-3065. Epub 2021 Apr 7.

Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Guangzhou, Guangdong, People's Republic of China.

Purpose: This study aimed to investigate AKT gene mutation status in Chinese breast cancer patients.

Methods: The study included 411 breast cancer patients hospitalized in Guangdong Provincial People's Hospital (GDPH) from June 1, 2017 to September 27, 2018. Mastectomy or breast conserving surgery was performed, and tissue samples were subjected to next-generation sequencing (NGS) to determine AKT gene mutation status. Meanwhile, the expression of human epidermal growth factor receptor 2 (Her2), progesterone receptor (PR), and estrogen receptor (ER) was analyzed by immunohistochemistry staining. The Cancer Genome Atlas (TCGA) database was used for comparative studies.

Results: Patients in the GDPH cohort had an older age ( < 0.001), higher postmenopausal rate ( < 0.001), larger tumor size ( < 0.001), higher histologic type of infiltrating duct cancer ( < 0.001), higher metastatic rate ( < 0.001), higher expression of ER ( = 0.015) and HER2 ( < 0.001), and higher percentage of the HR/HER2 subtype ( < 0.001) than those in the TCGA cohort. The GDPH cohort displayed lower rates of overall AKT and AKT3 mutation ( < 0.001), but a higher AKT1 mutation rate ( < 0.0001) compared with the TCGA cohort. Notably, the NGS studies identified missense mutation and copy number amplification as the most common AKT variation type in the GDPH and TCGA cohorts, respectively. Specifically, E17K mutation in AKT1 was predominantly detected in GDPH cohort, while being absent in TCGA cohort. Moreover, in the GDPH cohort, AKT variation was correlated with a number of clinicopathological variables, including age over 50, HER2-, HR+/HER2-, and PR+.

Conclusion: Patients in the GDPH cohort had lower rates of AKT and AKT3 mutation and higher AKT1 mutation rate than those in the TCGA cohort, while harboring missense mutations detected predominantly as E17K mutation in AKT1. In GDPH cohort, there were correlations between AKT mutation and the clinicopathological characteristics of patients.
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http://dx.doi.org/10.2147/CMAR.S299624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039050PMC
April 2021

A multi-center survey on the postpartum mental health of mothers and attachment to their neonates during COVID-19 in Hubei Province of China.

Ann Transl Med 2021 Mar;9(5):382

Health, Nutrition and WASH, UNICEF China, Beijing, China.

Background: There is an emerging literature on the mental health of both pre- and post-partum mothers during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: As of April 1, 2020, 23 mothers confirmed with COVID-19, 15 mothers suspected with COVID-19 but with negative polymerase chain reaction tests, and 33 mothers without COVID-19 (Control Group) were recruited for a study from Hubei Province in China. The Maternal Postnatal Attachment Scale (MPAS), the Zung Self-rating Anxiety Scale, and the Zung Self-rating Depression Scale were applied to investigate the attachment of mothers to their neonates and the postpartum mental health of mothers within the first 3 months after delivery (between 20 to 89 days).

Results: The period of mother-child separation among the confirmed group (33.9±20.9 days) was significantly longer than that of suspected group (16.7±12.2 days) and control group (10.7±8.4 days). The total score of the MPAS in mothers confirmed with COVID-19 (45.5±4.2) was significantly lower (indicating less mother-child attachment) than that in the suspected (50.5±4.7) and control (48.8±4.6) groups. A negative correlation was noted between the mother-child separation time and the MPAS scores, including the subscale scores of attachment (MPAS acore: Spearman's ρ =-0.33, 95% CI: -0.095 to -0.538, P=0.005; Subscale score of attachment: Spearman's ρ =-0.40, 95% CI: -0.163 to -0.592, P=0.001). The incidence of postpartum anxiety in the confirmed, suspected and control groups was 4.3%, 6.7% and 12.1%, respectively; and the incidence of postpartum depression was 39.1%, 33.3% and 30.3%, respectively. No significant difference was found with regards to maternal postpartum anxiety and depression among the three groups.

Conclusions: Decreased mother-child attachment found among mothers confirmed with COVID-19, indicates that further intervention is needed to ensure mother-child interaction to appropriately develop attachment. Mother-child attachment experienced disruption due to prolonged mother-child separation necessitated by the COVID-19 management protocol, which needs to be revised to reduce prolonged mother-child separation. Additionally, mothers with and without COVID-19 suffered a high incidence of depression, which warrants further mental health investment for pregnant mothers during the COVID-19 pandemic.
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http://dx.doi.org/10.21037/atm-20-6115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033344PMC
March 2021

Laparoscopic anterior hepatic transection for resecting lesions originating in the paracaval portion of the caudate lobe (with videos).

Surg Endosc 2021 Apr 9. Epub 2021 Apr 9.

Institute of Hepatobiliary Surgery, First Affiliated Hospital, Army Medical University, 30 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China.

Background: The paracaval portion of the caudate lobe is located in the core of the liver. Lesions originating in the paracaval portion often cling to or even invade major hepatic vascular structures. The traditional open anterior hepatic transection approach has been adopted to treat paracaval-originating lesions. With the development of laparoscopic surgery, paracaval-originating lesions are no longer an absolute contraindication for laparoscopic liver resection. This study aimed to evaluate the safety and feasibility of laparoscopic anterior hepatic transection for resecting paracaval-originating lesions.

Methods: This study included 15 patients who underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection between August 2017 and April 2020. The perioperative indicators, follow-up results, operative techniques and surgical indications were retrospectively evaluated.

Results: All patients underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection. The median operation time was 305 min (220-740 min), the median intraoperative blood loss was 400 ml (250-3600 ml), and the median length of postoperative hospital stay was 9 days (5-20 days). No conversion to laparotomy or perioperative deaths occurred. Six patients had Clavien grade III-IV complications (III/IV, 5/1). Two patients developed tumor recurrence after 13 months and 8 months.

Conclusion: Although technically challenging, laparoscopic anterior hepatic transection is still a safe and feasible procedure for resecting paracaval-originating lesions in select patients.
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http://dx.doi.org/10.1007/s00464-021-08455-5DOI Listing
April 2021

Immune Response and Hemolymph Microbiota of Apis mellifera and Apis cerana After the Challenge With Recombinant Varroa Toxic Protein.

J Econ Entomol 2021 Jun;114(3):1310-1320

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510260, Guangdong, China.

The honey bee is a significant crop pollinator and key model insect for understanding social behavior, disease transmission, and development. The ectoparasitic Varroa destructor mite put threats on the honey bee industry. A Varroa toxic protein (VTP) from the saliva of Varroa mites contributes to the toxicity toward Apis cerana and the deformed wing virus elevation in Apis mellifera. However, the immune response and hemolymph microbiota of honey bee species after the injection of recombinant VTP has not yet been reported. In this study, both A. cerana and A. mellifera worker larvae were injected with the recombinant VTP. Then the expressions of the honey bee immune genes abaecin, defensin, and domeless at three time points were determined by qRT-PCR, and hemolymph microbial community were analyzed by culture-dependent method, after recombinant VTP injection. The mortality rates of A. cerana larvae were much higher than those of A. mellifera larvae after VTP challenge. VTP injection induced the upregulation of defensin gene expression in A. mellifera larvae, and higher levels of abaecin and domeless mRNAs response in A. cerana larvae, compared with the control (without any injection). Phosphate buffer saline (PBS) injection also upregulated the expression levels of abaecin, defensin, and domeless in A. mellifera and A. cerana larvae. Three bacterial species (Enterococcus faecalis, Staphylococcus cohnii, and Bacillus cereus) were isolated from the hemolymph of A. cerana larvae after VTP injection and at 48 h after PBS injections. Two bacterial species (Stenotrophomonas maltophilia and Staphylococcus aureus) were isolated from A. mellifera larvae after VTP challenge. No bacterial colonies were detected from the larval hemolymph of both honey bee species treated by injection only and the control. The result indicates that abaecin, defensin, and domeless genes and hemolymph microbiota respond to the VTP challenge. VTP injection might induce the dramatic growth of different bacterial species in the hemolymph of the injected larvae of A. mellifera and A. cerana, which provide cues for further studying the interactions among the honey bee, VTP, and hemolymph bacteria.
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http://dx.doi.org/10.1093/jee/toab047DOI Listing
June 2021

Nanoplatform based on GSH-responsive mesoporous silica nanoparticles for cancer therapy and mitochondrial targeted imaging.

Mikrochim Acta 2021 Apr 6;188(5):154. Epub 2021 Apr 6.

Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, Hubei Key Laboratory of Polymer Materials, School of Materials Science & Engineering, Hubei University, Wuhan, 430062, China.

Mitochondria, as the energy factory of most cells, are not only responsible for the generation of adenosine triphosphoric acid (ATP) but also essential targets for therapy and diagnosis of various diseases, especially cancer. The safe and potential nanoplatform which can deliver various therapeutic agents to cancer cells and mitochondrial targeted imaging is urgently required. Herein, Au nanoparticles (AuNPs), mesoporous silica nanoparticles (MSN), cationic ligand (triphenylphosphine (TPP)), doxorubicin (DOX), and carbon nanodots (CDs) were utilized to fabricate mitochondrial targeting drug delivery system (denoted as CDs(DOX)@[email protected]). Since AuNPs, as the gatekeepers, can be etched by intracellular glutathione (GSH) via ligand exchange induced etching process, DOX can be released into cells in a GSH-dependent manner which results in the superior GSH-modulated tumor inhibition activity. Moreover, after etching by GSH, the CDs(DOX)@[email protected] can serve as promising fluorescent probe (λ = 633 nm, λ = 650 nm) for targeted imaging of mitochondria in living cells with near-infrared fluorescence. The induction of apoptosis derived from the membrane depolarization of mitochondria is the primary anti-tumor route of CDs(DOX)@[email protected] As a kind of GSH-responsive mitochondrial targeting nanoplatform, it holds great promising for effective cancer therapy and mitochondrial targeted imaging. The mitochondrial targeting drug delivery system was fabricated by AuNPs, MSN, TPP, and CDs. The nanoplatform can realize redox-responsive drug delivery and targeted imaging of mitochondria in living cells to improve the therapeutic efficiency and security.
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http://dx.doi.org/10.1007/s00604-021-04810-4DOI Listing
April 2021

A Novel Coverage Optimization Strategy Based on Grey Wolf Algorithm Optimized by Simulated Annealing for Wireless Sensor Networks.

Comput Intell Neurosci 2021 16;2021:6688408. Epub 2021 Mar 16.

School of Mathematics and Computer Science, Hubei University of Arts and Science, Xiangyang 441053, China.

The coverage optimization problem of wireless sensor network has become one of the hot topics in the current field. Through the research on the problem of coverage optimization, the coverage of the network can be improved, the distribution redundancy of the sensor nodes can be reduced, the energy consumption can be reduced, and the network life cycle can be prolonged, thereby ensuring the stability of the entire network. In this paper, a novel grey wolf algorithm optimized by simulated annealing is proposed according to the problem that the sensor nodes have high aggregation degree and low coverage rate when they are deployed randomly. Firstly, the mathematical model of the coverage optimization of wireless sensor networks is established. Secondly, in the process of grey wolf optimization algorithm, the simulated annealing algorithm is embedded into the grey wolf after the siege behavior ends and before the grey wolf is updated to enhance the global optimization ability of the grey wolf algorithm and at the same time improve the convergence rate of the grey wolf algorithm. Simulation experiments show that the improved grey wolf algorithm optimized by simulated annealing is applied to the coverage optimization of wireless sensor networks. It has better effect than particle swarm optimization algorithm and standard grey wolf optimization algorithm, has faster optimization speed, improves the coverage of the network, reduces the energy consumption of the nodes, and prolongs the network life cycle.
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http://dx.doi.org/10.1155/2021/6688408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990533PMC
March 2021